NCBI Conserved Domain Search

Intersectin and clathrin adaptor AP2 binding region; INTAP is a natively unstructured region of intersectin 1 proteins, lying between the first pair of SH3 domains, that binds to the clathrin adaptor AP2. This binding forms an intersectin-AP2 complex that functions as an important regulator of clathrin-mediated SV recycling in synapses.

Pssm-ID: 435467 Cd Length: 115 Bit Score: 225.14 E-value: 1.64e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  761 KIPENEVPAPVKPVTDSTsaPAPKLALRETPA-PLAV-TSSEPSTTPNNWADFSSTWPTSTNEKPETDNWDAWAAQPSLT 838
Cdd:pfam16617    1 KIPESEVPASVKPAADST--AAPKVALRETPTtPLAPpTSSESSTASNNWADFSSTWPTNSSEKAETDNWDAWAAQPSLT 78

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1061899772  839 VPSAGQLRQRSAFTPATATGSSPSPVLGQGEKVEGLQ 875
Cdd:pfam16617   79 VPSAGQLRQRSAFTPATVTGSSPSPVLGQGEKVEGLQ 115

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 156.28 E-value: 1.05e-44

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772   177 EWAVPQSSRLKYRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMHLIDVAMSGQ 256
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQDGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80

                            90
                    ....*....|....*.
gi 1061899772   257 PLPPVLPPEYIPPSFR 272
Cdd:smart00027   81 PIPASLPPSLIPPSKR 96

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212926 Cd Length: 65 Bit Score: 134.09 E-value: 3.25e-37

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1032 KKPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLLSP 1096
Cdd:cd11993      1 KKPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLLSP 65

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 131.27 E-value: 1.83e-36

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11987      1 YYRALYPFEARSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 55

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 131.63 E-value: 5.36e-36

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772    14 IWAITVEERAKHDQQFHSLKP-ISGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQVEFSIAMKLIKLKLQGY 92
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKnQDGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80

                            90
                    ....*....|....*.
gi 1061899772    93 QLPSALPPVMKQQPVA 108
Cdd:smart00027   81 PIPASLPPSLIPPSKR 96

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 125.91 E-value: 1.85e-34

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1036 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKL 1093
Cdd:cd11839      1 IAQVIAPFTATAENQLSLAVGQLVLVRKKSPSGWWEGELQARGKKRQIGWFPANYVKL 58

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 123.14 E-value: 1.43e-33

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1116 CQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11995      1 CQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQVGLFPSNYVKL 54

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 120.86 E-value: 9.86e-33

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11991      1 EYVAMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTVGDKTGVFPSNYVRP 52

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 116.69 E-value: 2.70e-31

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11836      1 KYRALYAFEARNPDEISFQPGDIIQVDESQVAEPGWLAGELKGKTGWFPANYVEK 55

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 114.05 E-value: 2.40e-30

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11840      1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVEP 53

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 111.73 E-value: 1.56e-29

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11989      1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 52

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 111.35 E-value: 1.67e-29

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11838      1 EYIALYPYESNEPGDLTFNAGDVILVTKKDGEWWTGTIGDRTGIFPSNYVRP 52

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 110.07 E-value: 5.60e-29

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1116 CQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11996      1 CQVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 54

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 106.30 E-value: 9.80e-28

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQ-GQKGWFPKSYVKL 926
Cdd:cd11837      1 TATALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELEgGEEGWFPKSYVKE 53

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 104.24 E-value: 7.90e-27

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772 1036 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLL 1094
Cdd:cd11994      1 IAQVTTAYVASGVEQLSLSPGQLILILKKNSSGWWLGELQARGKKRQKGWFPASHVKLL 59

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 103.20 E-value: 1.27e-26

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11990      1 KAQALCSWTAKKDNHLNFSKNDIITVLEQQENWWFGEVHGGRGWFPKSYVKL 52

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 100.76 E-value: 1.38e-25

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  188 YRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMHLIDVAMS 254
Cdd:cd00052      1 YDQIFRSLDPDGDGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 100.37 E-value: 1.98e-25

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772   26 DQQFHSLKPI-SGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQVEFSIAMKLIKLKLQ 90
Cdd:cd00052      2 DQIFRSLDPDgDGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 95.85 E-value: 4.62e-24

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd11992      1 EYIALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVR 51

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 91.47 E-value: 1.90e-22

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  706 VYYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11988      2 VNYRALYPFEARNHDEMSFNAGDIIQVDEKTVGEPGWLYGSFQGNFGWFPCNYVEK 57

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 88.75 E-value: 1.42e-21

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  1115 VCQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN-GQVGLFPSNYVK 1168
Cdd:smart00326    2 GPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 85.21 E-value: 2.70e-20

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN-GQVGLFPSNY 1166
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNgGREGLFPANY 51

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 81.91 E-value: 4.07e-19

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11805      1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYVQ 52

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 80.47 E-value: 1.50e-18

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11875      5 LFDYEAENEDELTLREGDIVTILSKDceDKGWWKGELNGKRGVFPDNFVEP 55

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 90.00 E-value: 5.12e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  326 LELEKRRQALLEQQRKEQERLAQLERAEQERKERERqEQERKRQLELEKQLEKQrelerqreeerrkeIERREAAKRELE 405
Cdd:COG1196    234 LRELEAELEELEAELEELEAELEELEAELAELEAEL-EELRLELEELELELEEA--------------QAEEYELLAELA 298

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  406 R-QRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRI 484
Cdd:COG1196    299 RlEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAE 378

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  485 AEithlqqqlqesqqmlgrlipEKQILNDQLKQVQQNSLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEID 564
Cdd:COG1196    379 EE--------------------LEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEE 438

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  565 IFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEK 644
Cdd:COG1196    439 EEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEGFLEGVKAALLLAG 518


                   ...
gi 1061899772  645 LKR 647
Cdd:COG1196    519 LRG 521

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 78.52 E-value: 6.04e-18

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11826      2 VVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNYV 51

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 78.15 E-value: 8.67e-18

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11823      6 YSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYV 51

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 76.15 E-value: 3.87e-17

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11766      5 KFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYV 51

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 74.81 E-value: 1.19e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1115 VCQVigMYDYTAQNDDELAFNKGQIINVLNK--EDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd12142      1 YCRV--LFDYNPVAPDELALKKGDVIEVISKetEDEGWWEGELNGRRGFFPDNFV 53

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 74.48 E-value: 1.50e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11950      1 QVRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANYVA 52

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 74.60 E-value: 1.59e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVklTTD 1172
Cdd:cd11964      2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGLFPSNFV--TAD 55

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 74.27 E-value: 1.78e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11877      1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVKE 53

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 73.93 E-value: 2.69e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKE-DPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11804      3 VAKHDFKATAEDELSFKKGSILKVLNMEdDPNWYKAELDGKEGLIPKNYI 52

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 73.91 E-value: 2.70e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1116 CQVIgmYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11874      2 CKVL--FSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVKE 53

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 73.59 E-value: 3.22e-16

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPD----WWKGEVNGQVGLFPS 1164
Cdd:cd11762      5 LYDYEAQSDEELSFPEGAIIRILRKDDNGvddgWWEGEFNGRVGVFPS 52

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 73.72 E-value: 3.25e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11949      2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVT 52

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 73.49 E-value: 3.78e-16

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11772      5 LYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYV 51

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 72.84 E-value: 6.49e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDG---DWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11842      3 VALYDFAGEQPGDLAFQKGDIITILKKSDsqnDWWTGRIGGREGIFPANYVEL 55

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 82.68 E-value: 1.08e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  371 ELEKQLEKqrelerqreeerrkeierreaakreLERQ-------RQLEWERNRRQ--ELLNQRNKEQEDIVVLKAKKKTL 441
Cdd:COG1196    197 ELERQLEP-------------------------LERQaekaeryRELKEELKELEaeLLLLKLRELEAELEELEAELEEL 251

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  442 EFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQ-VQQ 520
Cdd:COG1196    252 EAELEELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAElEEE 331

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  521 NSLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDifnnQLKELREIHNKQQLQKQKSMEAERLKQKEQER 600
Cdd:COG1196    332 LEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELA----EAEEELEELAEELLEALRAAAELAAQLEELEE 407

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  601 KIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRLFHQHQEPAK 680
Cdd:COG1196    408 AEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELA 487

                          330
                   ....*....|.
gi 1061899772  681 PAVQAPWSTAE 691
Cdd:COG1196    488 EAAARLLLLLE 498

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 71.88 E-value: 1.18e-15

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:pfam14604    2 LYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 71.47 E-value: 1.87e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1116 CQVIgmYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd12057      2 CKVL--FPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGRRGVFPDNFVKL 55

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.

Pssm-ID: 289529 Cd Length: 104 Bit Score: 72.79 E-value: 2.26e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  187 KYRQLFNSHdKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMHLIDVAMSG--QPLPPVLPP 264
Cdd:pfam12763   11 KYWEIFSGL-KPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLIFDLVNGniADVPDELPD 89


                   ....*.
gi 1061899772  265 EYIPPS 270
Cdd:pfam12763   90 WLVPGS 95

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 71.08 E-value: 2.43e-15

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN-GQVGLFPS 1164
Cdd:pfam00018    3 LYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKgGKEGLIPS 47

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 71.03 E-value: 2.47e-15

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772   872 EGLQAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQ-GQKGWFPKSYVK 925
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDdGWWKGRLGrGKEGLFPSNYVE 56

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 70.64 E-value: 4.26e-15

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772   961 SGEEFIAMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGD-KAGVFPSNYVR 1014
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKsDDGWWKGRLGRgKEGLFPSNYVE 56

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 70.26 E-value: 4.51e-15

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772   704 KVVYYRALYPFESRSHDEITIQPGDIVMVDEsqTGEPGWLGGELK-GKTGWFPANYAE 760
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLE--KSDDGWWKGRLGrGKEGLFPSNYVE 56

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 70.23 E-value: 5.65e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE-VNGQVGLFPSNYV 1167
Cdd:cd11812      2 VVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSlVNGQQGYFPANYV 52

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 80.10 E-value: 6.41e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLPV---TFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQER-----KRQ 369
Cdd:TIGR02168  218 LKAELRELELALLVlrlEELREELEELQEELKEAEEELEELTAELQELEEKLEELRLEVSELEEEIEELQKElyalaNEI 297

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  370 LELEKQLEKQRELERqreeerrkeierreAAKRELER-QRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEAL 448
Cdd:TIGR02168  298 SRLEQQKQILRERLA--------------NLERQLEElEAQLEELESKLDELAEELAELEEKLEELKEELESLEAELEEL 363

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  449 NDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDsL 528
Cdd:TIGR02168  364 EAELEELESRLEELEEQLETLRSKVAQLELQIASLNNEIERLEARLERLEDRRERLQQEIEELLKKLEEAELKELQAE-L 442

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  529 VTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELR-EIHNKQQLQKQKSMEAERLKQKEQERK 601
Cdd:TIGR02168  443 EELEEELEELQEELERLEEALEELREELEEAEQALDAAERELAQLQaRLDSLERLQENLEGFSEGVKALLKNQS 516

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 70.05 E-value: 6.80e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVklTTDM 1173
Cdd:cd11963      3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRGVGLFPSNFV--TTDL 57

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.

Pssm-ID: 289529 Cd Length: 104 Bit Score: 71.25 E-value: 8.40e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772   21 ERAKHDQQFHSLKPISGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQVEFSIAMKLIKLKLQGYQ--LPSAL 98
Cdd:pfam12763    8 EIKKYWEIFSGLKPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLIFDLVNGNIadVPDEL 87


                   .
gi 1061899772   99 P 99
Cdd:pfam12763   88 P 88

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 69.68 E-value: 8.90e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11823      3 KALYSYTANREDELSLQPGDIIEVHEKQ--DDGWWLGELNGKKGIFPATYVE 52

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 69.67 E-value: 9.02e-15

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQ-VGLFPSNYVK 1168
Cdd:cd11825      5 LYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKkQKWFPANYVE 53

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 79.60 E-value: 9.23e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  318 RENFERGNL---ELEKRRQALlEQQR---------KEQERLAQLERAEQERKERERQEQERKRQL-ELEKQLEKQReler 384
Cdd:COG1196    185 EENLERLEDilgELERQLEPL-ERQAekaeryrelKEELKELEAELLLLKLRELEAELEELEAELeELEAELEELE---- 259

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  385 qreeerrkeierreAAKRELERQRQLEweRNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQdirc 464
Cdd:COG1196    260 --------------AELAELEAELEEL--RLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLE---- 319

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  465 RLTTQRQEIEstnksrelriAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQnslhrdSLVTLKRALEAKELARQH 544
Cdd:COG1196    320 ELEEELAELE----------EELEELEEELEELEEELEEAEEELEEAEAELAEAEE------ALLEAEAELAEAEEELEE 383

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  545 LRDQLDEVEKETRSKLQEIdifnNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWL 624
Cdd:COG1196    384 LAEELLEALRAAAELAAQL----EELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEE 459

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 1061899772  625 EHVQQEDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQD 666
Cdd:COG1196    460 ALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEA 501

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 79.33 E-value: 1.25e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  311 VTFEDKKREN--FERGNlELEKrrqalLEQQRKEQERLA------------QLERAEQERKERERQEQERKRQL-ELEKQ 375
Cdd:TIGR02168  661 ITGGSAKTNSsiLERRR-EIEE-----LEEKIEELEEKIaelekalaelrkELEELEEELEQLRKELEELSRQIsALRKD 734

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  376 LEK-QRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQ 454
Cdd:TIGR02168  735 LARlEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEELKALREALDELRAELTL 814

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  455 LEGKLQDIRCRLTTQRQEIESTNKS---RELRIAEITHLQQQLQESQQMLGRLIPEkqiLNDQLKQVQQnslhrdslvtl 531
Cdd:TIGR02168  815 LNEEAANLRERLESLERRIAATERRledLEEQIEELSEDIESLAAEIEELEELIEE---LESELEALLN----------- 880

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  532 krALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQK-SMEAERLKQKEQERKIIELEKQKE 610
Cdd:TIGR02168  881 --ERASLEEALALLRSELEELSEELRELESKRSELRRELEELREKLAQLELRLEGlEVRIDNLQERLSEEYSLTLEEAEA 958

                          330
                   ....*....|..
gi 1061899772  611 EAQRRAQERDKQ 622
Cdd:TIGR02168  959 LENKIEDDEEEA 970

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 69.03 E-value: 1.30e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11820      2 KVRALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGLFPANFVT 53

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 68.60 E-value: 2.18e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11959      3 VALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCRGKYGLFPANYVEL 53

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 68.60 E-value: 2.24e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDP--DWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11842      1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSqnDWWTGRIGGREGIFPANYVEL 55

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 68.29 E-value: 2.28e-14

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11951      6 YDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISGRVGFFPRNYV 51

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 78.05 E-value: 2.45e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLE 377
Cdd:COG1196    389 LEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAEL 468

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  378 KQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDkkHQLEG 457
Cdd:COG1196    469 LEEAALLEAALAELLEELAEAAARLLLLLEAEADYEGFLEGVKAALLLAGLRGLAGAVAVLIGVEAAYEAALE--AALAA 546

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  458 KLQDIRCRLTTQRQEIESTNKSRELRIAEI----------THLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDS 527
Cdd:COG1196    547 ALQNIVVEDDEVAAAAIEYLKAAKAGRATFlpldkiraraALAAALARGAIGAAVDLVASDLREADARYYVLGDTLLGRT 626

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  528 LVTLkRALEAKELARQH---LRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIE 604
Cdd:COG1196    627 LVAA-RLEAALRRAVTLagrLREVTLEGEGGSAGGSLTGGSRRELLAALLEAEAELEELAERLAEEELELEEALLAEEEE 705

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  605 LEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRL 671
Cdd:COG1196    706 ERELAEAEEERLEEELEEEALEEQLEAEREELLEELLEEEELLEEEALEELPEPPDLEELERELERL 772

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 67.82 E-value: 3.16e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1116 CQVIgmYDYTAQNDDELAFNKGQIINVLnKEDPD-WWKGEVNGQVGLFPSNYV 1167
Cdd:cd11827      2 CKAL--YAYDAQDTDELSFNEGDIIEIL-KEDPSgWWTGRLRGKEGLFPGNYV 51

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 67.56 E-value: 4.22e-14

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  1033 KPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELqargKKRQIGWFPANYVK 1092
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRL----GRGKEGLFPSNYVE 56

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 77.49 E-value: 4.31e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  294 EEPVLEDEQQQLEKKLPVtfeDKKRENFERGNLELEKRRQallEQQRKEQERLAQLERAEQERKERERQEQERKRQLELE 373
Cdd:PTZ00121  1351 EAEAAADEAEAAEEKAEA---AEKKKEEAKKKADAAKKKA---EEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAK 1424

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  374 KQLEKQRELERQREEERRKEIERReaAKRELERQRQLE-----WERNRRQELLNQRNKEQEDivVLKAKKKTLEFELEAL 448
Cdd:PTZ00121  1425 KKAEEKKKADEAKKKAEEAKKADE--AKKKAEEAKKAEeakkkAEEAKKADEAKKKAEEAKK--ADEAKKKAEEAKKKAD 1500

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  449 NDKKHQLEGKLQDiRCRLTTQRQEIESTNKSRELRIAEitHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDSL 528
Cdd:PTZ00121  1501 EAKKAAEAKKKAD-EAKKAEEAKKADEAKKAEEAKKAD--EAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKN 1577

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  529 VTLKRALEAK--ELARQHLRDQLDEVEK-----------ETRSKLQEIDIFNNQLKELREIHNKQQLQKQKS-----MEA 590
Cdd:PTZ00121  1578 MALRKAEEAKkaEEARIEEVMKLYEEEKkmkaeeakkaeEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAeelkkAEE 1657

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  591 ERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRP----RKLHEEEK-----LKREESVKKKDGEEKGK 661
Cdd:PTZ00121  1658 ENKIKAAEEAKKAEEDKKKAEEAKKAEEDEKKAAEALKKEAEEAKKaeelKKKEAEEKkkaeeLKKAEEENKIKAEEAKK 1737

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|
gi 1061899772  662 QEAQDKLGRLFHQHQEPAKPAVQAPWSTAEKGPLTISAQE 701
Cdd:PTZ00121  1738 EAEEDKKKAEEAKKDEEEKKKIAHLKKEEEKKAEEIRKEK 1777

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 67.49 E-value: 4.85e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGD-KAGVFPSNY 1012
Cdd:cd00174      2 ARALYDYEAQDDDELSFKKGDIITVLEKdDDGWWEGELNGgREGLFPANY 51

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 67.28 E-value: 5.07e-14

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11803      6 LYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQSGFFPVNYV 52

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 67.29 E-value: 5.18e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11873      2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMFPDNFVK 52

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 67.01 E-value: 6.97e-14

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11824      5 LYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYLEK 53

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 66.79 E-value: 9.81e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1115 VCQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11956      1 EVEAVACFDYTGRTAQELSFKRGDVLLLHSKASSDWWRGEHNGMRGLIPHKYISV 55

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 66.39 E-value: 1.05e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11961      2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSRGLFPSNYVEL 53

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 65.95 E-value: 1.60e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQ-GQKGWFPKSY 923
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDgWWEGELNgGREGLFPANY 51

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 75.56 E-value: 1.84e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  291 RLPEEPVLEDEQQQLEKKLPVTfEDKKRENFERGNLELEKRRqallEQQRKEQERLAQleRAEQERKERERQEQERKRQl 370
Cdd:PTZ00121  1284 KKAEEKKKADEAKKAEEKKKAD-EAKKKAEEAKKADEAKKKA----EEAKKKADAAKK--KAEEAKKAAEAAKAEAEAA- 1355

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  371 elEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQ----RNKEQEDIVVLKAKKKTLEFELE 446
Cdd:PTZ00121  1356 --ADEAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKKKADEAKKKAEEDKKKadelKKAAAAKKKADEAKKKAEEKKKA 1433

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  447 ALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRD 526
Cdd:PTZ00121  1434 DEAKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKKADEAKKAAEAKKKAD 1513

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  527 SLVTLKRALEAKELARQHLRDQLDEVEK-ETRSKLQEIdifnNQLKELREIHNKQQLQKQKSME---------AERLKQK 596
Cdd:PTZ00121  1514 EAKKAEEAKKADEAKKAEEAKKADEAKKaEEKKKADEL----KKAEELKKAEEKKKAEEAKKAEedknmalrkAEEAKKA 1589

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  597 EQER-----KIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHqrpRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRL 671
Cdd:PTZ00121  1590 EEARieevmKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEE---KKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAEE 1666

                          410       420
                   ....*....|....*....|.
gi 1061899772  672 FHQHQEPAKPAVQAPWSTAEK 692
Cdd:PTZ00121  1667 AKKAEEDKKKAEEAKKAEEDE 1687

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 65.73 E-value: 1.91e-13

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11805      4 ALYDFNPQEPGELEFRRGDIITVLDSsDPDWWKGELRGRVGIFPANYV 51

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 65.68 E-value: 2.14e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNY 1166
Cdd:cd11845      1 IYVALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARhlSTGKEGYIPSNY 52

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 65.03 E-value: 2.93e-13

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQ---VGLFPSNY 1166
Cdd:cd11821      5 LYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGDpsrRGVFPVSF 53

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 64.92 E-value: 3.59e-13

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12052      6 FDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRRGLFPDNFVR 52

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 65.11 E-value: 3.86e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILV---TKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11841      4 ALYSFEGQQPCDLSFQAGDRITVltrTDSQFDWWEGRLRGRVGIFPANYV 53

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 64.67 E-value: 4.18e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11781      3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGRVGIFPASYVEI 53

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 64.92 E-value: 4.29e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1115 VCQVIGmyDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:pfam07653    1 YGRVIF--DYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVEE 53

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 64.64 E-value: 5.00e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN-GQVGLFPSNYVKL 1169
Cdd:cd11819      3 KALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNAkGQKGLFPANYVEL 54

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 64.84 E-value: 5.13e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKE-----DPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11876      5 LFDYDARGEDELTLRRGQPVEVLSKDaavsgDEGWWTGKIGDKVGIFPSNYV 56

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 64.41 E-value: 5.15e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1036 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQargkKRQIGWFPANY 1090
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELN----GGREGLFPANY 51

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 64.41 E-value: 6.02e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDEsqTGEPGWLGGEL-KGKTGWFPANY 758
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLE--KDDDGWWEGELnGGREGLFPANY 51

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 64.47 E-value: 6.75e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1115 VCQViGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKLT 1170
Cdd:cd12073      1 ICAV-ALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGLFPANYVELL 55

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 64.29 E-value: 7.11e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11875      1 KARVLFDYEAENEDELTLREGDIVTILSKDCEDKGWWKGELNGKRGVFPDNFVE 54

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 64.34 E-value: 7.21e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDP--DWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11841      1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSqfDWWEGRLRGRVGIFPANYVS 54

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 64.26 E-value: 8.08e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11972      4 KVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVE 55

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 73.25 E-value: 8.36e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  314 EDKKRENfERGNLELEKRRQALLEQQRKEQERLAQLER-AEQERK--ERERQEQERKRQLELEKQLEK-----QRELERQ 385
Cdd:PTZ00121  1402 EDKKKAD-ELKKAAAAKKKADEAKKKAEEKKKADEAKKkAEEAKKadEAKKKAEEAKKAEEAKKKAEEakkadEAKKKAE 1480

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  386 REEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEDiVVLKAKKKTLEFELEALNDKKHQLEGKLQDiRCR 465
Cdd:PTZ00121  1481 EAKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKAD-EAKKAEEAKKADEAKKAEEKKKADELKKAE-ELK 1558

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  466 LTTQRQEIESTNKSRE-----LRIAEITHLQQQLQESQQMLgRLIPEKQILNDQLKQVQQNSLHRDSLvtlKRALEAKEL 540
Cdd:PTZ00121  1559 KAEEKKKAEEAKKAEEdknmaLRKAEEAKKAEEARIEEVMK-LYEEEKKMKAEEAKKAEEAKIKAEEL---KKAEEEKKK 1634

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  541 ARQHLRDQLDEVEK--ETRSKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKiiELEKQKEEAQRRAQE 618
Cdd:PTZ00121  1635 VEQLKKKEAEEKKKaeELKKAEEENKIKAAEEAKKAEEDKKKAEEAKKAEEDEKKAAEALKKE--AEEAKKAEELKKKEA 1712

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  619 RDKQWLEHVQQEDEHqrpRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRLFHQHQEPAKPAVQAPWSTAEKG 693
Cdd:PTZ00121  1713 EEKKKAEELKKAEEE---NKIKAEEAKKEAEEDKKKAEEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEE 1784

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 63.79 E-value: 8.90e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 760
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEES--EDGWWEGINTGRTGLVPANYVE 49

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 73.17 E-value: 9.47e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  402 RELERQ-RQLEWERNRRQELLNQRNKEQE--------DIVVLKAKKKTLEFELEALNDKKHQLEGKLQdircRLTTQRQE 472
Cdd:TIGR02168  196 NELERQlKSLERQAEKAERYKELKAELRElelallvlRLEELREELEELQEELKEAEEELEELTAELQ----ELEEKLEE 271

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  473 IESTNKSRELRIAEITHLQQQLQESQQmlgRLIPEKQILNDQLKQVQQNSLHRD-SLVTLKRALEAKELARQHLRDQLDE 551
Cdd:TIGR02168  272 LRLEVSELEEEIEELQKELYALANEIS---RLEQQKQILRERLANLERQLEELEaQLEELESKLDELAEELAELEEKLEE 348

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  552 VEKETRSKLQEIDIFNNQLKELREIHN--KQQLQKQKSMEAERLKQKEQERK-IIELEKQKEEAQRRAQERDKQWLEHVQ 628
Cdd:TIGR02168  349 LKEELESLEAELEELEAELEELESRLEelEEQLETLRSKVAQLELQIASLNNeIERLEARLERLEDRRERLQQEIEELLK 428

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  629 QEDEHQR-------PRKLHEEEKLK-----REESVKKKDGEEKGKQEAQDKLGRLFHQHQ 676
Cdd:TIGR02168  429 KLEEAELkelqaelEELEEELEELQeelerLEEALEELREELEEAEQALDAAERELAQLQ 488

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 63.89 E-value: 9.53e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11971      1 KVVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGLFPGNYVE 52

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 63.52 E-value: 1.10e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11823      1 RCKALYSYTANREDELSLQPGDIIEVHEKQdDGWWLGELNGKKGIFPATYV 51

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 63.55 E-value: 1.12e-12

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12061      6 FNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVR 52

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 63.59 E-value: 1.25e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEVNGQVGLFPSNYV 1167
Cdd:cd11843      2 VRALYDYEGQESDELSFKAGDILTKLEEEDEQgWCKGRLDGRVGLYPANYV 52

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 63.42 E-value: 1.29e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11894      2 VKALYDYEGQTDDELSFPEGAIIRILNKENQDddgFWEGEFNGRIGVFPSVLVE 55

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 72.87 E-value: 1.36e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  314 EDKKRENFERGNLELEKRRQAL--LEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEErr 391
Cdd:PTZ00121  1455 EAKKAEEAKKKAEEAKKADEAKkkAEEAKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEE-- 1532

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  392 keierreaaKRELERQRQLEWERNRRQELLNQRNKEQEDivVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQ 471
Cdd:PTZ00121  1533 ---------AKKADEAKKAEEKKKADELKKAEELKKAEE--KKKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVMKLY 1601

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  472 EIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPE-KQILNDQLKQVQQNSLHRDSLVTLKRALEAKELARQHLRDQLD 550
Cdd:PTZ00121  1602 EEEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQlKKKEAEEKKKAEELKKAEEENKIKAAEEAKKAEEDKKKAEEAK 1681

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  551 EVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKsmeAERLKQKEQERKIielekQKEEAQRRAQERDKQWLEHVQQE 630
Cdd:PTZ00121  1682 KAEEDEKKAAEALKKEAEEAKKAEELKKKEAEEKKK---AEELKKAEEENKI-----KAEEAKKEAEEDKKKAEEAKKDE 1753

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|.
gi 1061899772  631 DEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRL 671
Cdd:PTZ00121  1754 EEKKKIAHLKKEEEKKAEEIRKEKEAVIEEELDEEDEKRRM 1794

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 63.10 E-value: 1.40e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11877      4 AKFNFEGTNEDELSFDKGDIITVTQVvEGGWWEGTLNGKTGWFPSNYVKE 53

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 63.20 E-value: 1.73e-12

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11840      3 IALFPYTAQNEDELSFQKGDIInVLSKDDPDWWRGELNGQTGLFPSNYV 51

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 72.02 E-value: 1.77e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  313 FEDKKRENFErgnlELEKRRQALLEQQRKEQERLAQLERAEQER--KERERQEQERKRQLEL-EKQLEKQRELERQREEE 389
Cdd:TIGR02169  168 FDRKKEKALE----ELEEVEENIERLDLIIDEKRQQLERLRRERekAERYQALLKEKREYEGyELLKEKEALERQKEAIE 243

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  390 RRKEIERREAAKRELERQrQLEWERNRRQELLNQRNKE-----QEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDirc 464
Cdd:TIGR02169  244 RQLASLEEELEKLTEEIS-ELEKRLEEIEQLLEELNKKikdlgEEEQLRVKEKIGELEAEIASLERSIAEKERELED--- 319

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  465 rLTTQRQEIESTNKSRELRIAEIThlqqqlqesqqmlgRLIPEKQILNDQLKQVQQNSlhRDSLVTLKRALEAKELARQH 544
Cdd:TIGR02169  320 -AEERLAKLEAEIDKLLAEIEELE--------------REIEEERKRRDKLTEEYAEL--KEELEDLRAELEEVDKEFAE 382

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  545 LRDQLDEVEKetrsklqEIDIFNNQLKEL-REIHNKQQLQKQKSMEAERLKQK-------------EQERKIIELEKQKE 610
Cdd:TIGR02169  383 TRDELKDYRE-------KLEKLKREINELkRELDRLQEELQRLSEELADLNAAiagieakineleeEKEDKALEIKKQEW 455

                          330       340       350
                   ....*....|....*....|....*....|....*...
gi 1061899772  611 EAQRRAQERDKQWLEHVQQEDEHQRPRKlhEEEKLKRE 648
Cdd:TIGR02169  456 KLEQLAADLSKYEQELYDLKEEYDRVEK--ELSKLQRE 491

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 63.30 E-value: 1.77e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd12056      7 LFHYEGTNEDELDFKEGEIILIISKDtgEPGWWKGELNGKEGVFPDNFVSQ 57

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 63.12 E-value: 1.79e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKE-DPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11946      2 EAIAKYDFKATADDELSFKRGDILKVLNEEcDQNWYKAELNGKDGFIPKNYIEM 55

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 63.09 E-value: 1.88e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVT-KKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11772      2 FRALYDYEAQHPDELSFEEGDLLYISdKSDPNWWKATCGGKTGLIPSNYV 51

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 63.06 E-value: 1.89e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1116 CQVigMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12054      3 CKV--LFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVK 53

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 72.10 E-value: 1.95e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  289 DQRLPEEPVLEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERE-RQEQERK 367
Cdd:PTZ00121  1455 EAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEaKKAEEAK 1534

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  368 RQLELEKQLEKQRELERQREEERRKEIErreaaKRELERQRQLEWERN---RRQELLNQRNKEQ-EDIVVLKAKKKTLEF 443
Cdd:PTZ00121  1535 KADEAKKAEEKKKADELKKAEELKKAEE-----KKKAEEAKKAEEDKNmalRKAEEAKKAEEARiEEVMKLYEEEKKMKA 1609

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  444 E----LEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEithlqqqlqesqqmlgrliPEKQILNDQLKqvq 519
Cdd:PTZ00121  1610 EeakkAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAE-------------------EENKIKAAEEA--- 1667

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  520 qnslhrdslvtlKRALEAKELARQHLRDQLDEVEKETRSKLQEidifnNQLKELREIHNKQQLQKQKsmeAERLKQKEQE 599
Cdd:PTZ00121  1668 ------------KKAEEDKKKAEEAKKAEEDEKKAAEALKKEA-----EEAKKAEELKKKEAEEKKK---AEELKKAEEE 1727

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  600 RKII--ELEKQKEEAQRRAQ-----ERDKQWLEHVQQEDEHQRPRKLHEEEKLKREE 649
Cdd:PTZ00121  1728 NKIKaeEAKKEAEEDKKKAEeakkdEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEE 1784

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 62.38 E-value: 2.52e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDpDWWKGEV-NGQVGLFPSNYVKL 1169
Cdd:cd11837      1 TATALYPWRAKKENHLSFAKGDIITVLEQQE-MWWFGELeGGEEGWFPKSYVKE 53

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 61.99 E-value: 3.70e-12

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11786      4 ALYNYEGKEPGDLSFKKGDIILLRKRiDENWYHGECNGKQGFFPASYV 51

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 61.95 E-value: 3.72e-12

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11826      3 VALYDYTADKDDELSFQEGDIIYVTKKNDDgWYEGVLNGVTGLFPGNYV 51

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 62.05 E-value: 3.99e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVlNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11838      3 IALYPYESNEPGDLTFNAGDVILV-TKKDGEWWTGTIGDRTGIFPSNYVRP 52

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 70.18 E-value: 4.69e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL-ELEKQL 376
Cdd:COG4717    100 LEEELEELEAELEELREELEKLEKLLQLLPLYQELEALEAELAELPERLEELEERLEELRELEEELEELEAELaELQEEL 179

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  377 EKQRELERQREEERRKEierreaAKRELERQRQlewernRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLE 456
Cdd:COG4717    180 EELLEQLSLATEEELQD------LAEELEELQQ------RLAELEEELEEAQEELEELEEELEQLENELEAAALEERLKE 247

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  457 GK----LQDIRCRLTTQRQEIESTnksrELRIAEIThlQQQLQESQQMLGRLIPEKQILNDQLKQVQ----QNSLHRDSL 528
Cdd:COG4717    248 ARllllIAAALLALLGLGGSLLSL----ILTIAGVL--FLVLGLLALLFLLLAREKASLGKEAEELQalpaLEELEEEEL 321

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  529 VTLKRALEAK-ELARQHLRDQLDEVEkETRSKLQEIDIFNNQLKELREIHNKQQLQKQK--SMEAERLKQKEQERKIIEL 605
Cdd:COG4717    322 EELLAALGLPpDLSPEELLELLDRIE-ELQELLREAEELEEELQLEELEQEIAALLAEAgvEDEEELRAALEQAEEYQEL 400

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772  606 EKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHE-EEKLKREE 649
Cdd:COG4717    401 KEELEELEEQLEELLGELEELLEALDEEELEEELEElEEELEELE 445

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 70.48 E-value: 4.75e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  293 PEEPVLEDEQQQLEK------KLPVTFEDKKRENFER-GNL--------ELEKRRQALLEQQRKEQERLAQLERAEQERK 357
Cdd:PRK03918   214 SELPELREELEKLEKevkeleELKEEIEELEKELESLeGSKrkleekirELEERIEELKKEIEELEEKVKELKELKEKAE 293

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  358 ERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKA- 436
Cdd:PRK03918   294 EYIKLSEFYEEYLDELREIEKRLSRLEEEINGIEERIKELEEKEERLEELKKKLKELEKRLEELEERHELYEEAKAKKEe 373

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  437 -----KKKT------LEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKS-RELRIAEITHLQQQLQESQQMLGRL 504
Cdd:PRK03918   374 lerlkKRLTgltpekLEKELEELEKAKEEIEEEISKITARIGELKKEIKELKKAiEELKKAKGKCPVCGRELTEEHRKEL 453

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  505 IPE-----KQILNDQLKQVQQNSLHRDSLVTLKRAL-EAKELARQH-LRDQLDEVEKETRS-KLQEIDIFNNQLKELREI 576
Cdd:PRK03918   454 LEEytaelKRIEKELKEIEEKERKLRKELRELEKVLkKESELIKLKeLAEQLKELEEKLKKyNLEELEKKAEEYEKLKEK 533

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  577 HNKQQlQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQwLEHVQQEDEHQRPRKLHEEEKLKRE 648
Cdd:PRK03918   534 LIKLK-GEIKSLKKELEKLEELKKKLAELEKKLDELEEELAELLKE-LEELGFESVEELEERLKELEPFYNE 603

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 61.71 E-value: 5.23e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKE-----DPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd12059      5 VFDYEASAEDELTLRRGDRVEVLSKDsavsgDEGWWTGKINDRVGIFPSNYV 56

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 61.74 E-value: 5.78e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12046      1 QVVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKGKIGIFPSAFVE 52

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 61.56 E-value: 5.94e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11877      2 VRAKFNFEGTNEDELSFDKGDIITV--TQVVEGGWWEGTLNGKTGWFPSNYVK 52

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 61.56 E-value: 6.70e-12

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12060      8 FNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYVR 54

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 61.71 E-value: 6.75e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKD----GD--WWTGTVGDKAGVFPSNYVR 1014
Cdd:cd12059      4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsGDegWWTGKINDRVGIFPSNYVT 57

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 60.94 E-value: 9.18e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd12142      1 YCRVLFDYNPVAPDELALKKGDVIEVISKETEDEGWWEGELNGRRGFFPDNFVM 54

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 60.99 E-value: 1.07e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKD----GD--WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11876      4 ALFDYDARGEDELTLRRGQPVEVLSKDaavsGDegWWTGKIGDKVGIFPSNYV 56

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 60.78 E-value: 1.16e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1116 CQVigMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12055      2 CQV--AFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIK 52

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 60.81 E-value: 1.20e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNK--EDPDWWK-GEVNGQVGLFPSNYVKL 1169
Cdd:cd11904      3 VQALYPFSSSNDEELNFEKGEVMDVIEKpeNDPEWWKcRKANGQVGLVPKNYVTV 57

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 60.49 E-value: 1.23e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV-NGQVGLFPSNYVKL 1169
Cdd:cd11960      5 LYDYQAADDTEISFDPGDIITDIEQIDEGWWRGTGpDGTYGLFPANYVEL 54

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 60.78 E-value: 1.25e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11772      2 FRALYDYEAQHPDELSFEEGDLLYISDKS--DPNWWKATCGGKTGLIPSNYVE 52

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 60.72 E-value: 1.25e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKE-DPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11830      3 KARYDFCARDMRELSLKEGDVVKIYNKKgQQGWWRGEINGRIGWFPSTYVE 53

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 60.62 E-value: 1.32e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVG-LFPSNYVK 1168
Cdd:cd11969      2 VKALYDYRAKRSDELSFCKGALIHNVSKETGGWWKGDYGGKVQhYFPSNYVE 53

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 69.00 E-value: 1.35e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  287 SVDQRLPEEPVLEDEQQQLEKKLpvtfEDKKRENFERGNL-ELEKRRQALLEQQRK---EQERLA-----QLERAEQERK 357
Cdd:pfam17380  283 AVSERQQQEKFEKMEQERLRQEK----EEKAREVERRRKLeEAEKARQAEMDRQAAiyaEQERMAmererELERIRQEER 358

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  358 ERErqeQERKRQLELEKQLEKQrelerqreeerrkeierreaakRELERqrqLEWERNRRQELLNQrnkeqedivvlkak 437
Cdd:pfam17380  359 KRE---LERIRQEEIAMEISRM----------------------RELER---LQMERQQKNERVRQ-------------- 396

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  438 kktlefELEALNDKKHQLEGKLQDIRcrltTQRQEIESTNKSRElriaeithlqqqlqesqqmlgrlipekqilndQLKQ 517
Cdd:pfam17380  397 ------ELEAARKVKILEEERQRKIQ----QQKVEMEQIRAEQE--------------------------------EARQ 434

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  518 VQQNSLHRDSLVTLKRALEaKELARQHLRDQLDEVEKETRSKLQEIDifnnqlkelREIHNKQQLQKQKSMEAERlKQKE 597
Cdd:pfam17380  435 REVRRLEEERAREMERVRL-EEQERQQQVERLRQQEEERKRKKLELE---------KEKRDRKRAEEQRRKILEK-ELEE 503

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  598 QERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRLFHQHQE 677
Cdd:pfam17380  504 RKQAMIEEERKRKLLEKEMEERQKAIYEEERRREAEEERRKQQEMEERRRIQEQMRKATEERSRLEAMEREREMMRQIVE 583

                          410
                   ....*....|..
gi 1061899772  678 PAKPAVQAPWST 689
Cdd:pfam17380  584 SEKARAEYEATT 595

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 60.59 E-value: 1.36e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLnKEDP--DWWKGEVNGQVGLFPSNY 1166
Cdd:cd11778      2 VEALYDYEAQGDDEISIRVGDRIAVI-RGDDgsGWTYGEINGVKGLFPTSY 51

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 60.40 E-value: 1.38e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNK--EDPDWWKGE-VNGQVGLFPSNYVKL 1169
Cdd:cd11767      2 VVALYPFTGENDEELSFEKGERLEIIEKpeDDPDWWKARnALGTTGLVPRNYVEV 56

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 60.61 E-value: 1.39e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYA 759
Cdd:cd12056      3 YCKALFHYEGTNEDELDFKEGEIILIISKDTGEPGWWKGELNGKEGVFPDNFV 55

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 60.34 E-value: 1.59e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKE-----DPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd12058      5 LYDYEASGEDELSLRRGDVVEVLSQDaavsgDDGWWAGKIRHRLGIFPANYV 56

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 60.41 E-value: 1.61e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1036 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKL 1093
Cdd:cd11877      1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGK-----TGWFPSNYVKE 53

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 60.38 E-value: 1.73e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQII-NVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11882      1 RARALYACKAEDESELSFEPGQIItNVQPSDEPGWLEGTLNGRTGLIPENYVEF 54

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 69.01 E-value: 1.98e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  314 EDKKRENFERGNLELEK----------RRQALL--EQQRKEQErlaqLERAEQERKERE-RQEQERKRQLELEKQLEKQR 380
Cdd:PTZ00121  1240 EEAKKAEEERNNEEIRKfeearmahfaRRQAAIkaEEARKADE----LKKAEEKKKADEaKKAEEKKKADEAKKKAEEAK 1315

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  381 ELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEdivvlkaKKKTLEFELEALNDKKHQLEGKLQ 460
Cdd:PTZ00121  1316 KADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEE-------KAEAAEKKKEEAKKKADAAKKKAE 1388

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  461 DIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQmlgrlipEKQILNDQLKQVQQNSlhrdslvtlKRALEAKEL 540
Cdd:PTZ00121  1389 EKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKA-------EEKKKADEAKKKAEEA---------KKADEAKKK 1452

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  541 ARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKsmeAERLKQKEQERKIIELEKQKEEAQ-----RR 615
Cdd:PTZ00121  1453 AEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKK---ADEAKKAAEAKKKADEAKKAEEAKkadeaKK 1529

                          330       340       350
                   ....*....|....*....|....*....|....*.
gi 1061899772  616 AQERDKQwlEHVQQEDEHQRPRKLHEEEKLKREESV 651
Cdd:PTZ00121  1530 AEEAKKA--DEAKKAEEKKKADELKKAEELKKAEEK 1563

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212743 [Multi-domain] Cd Length: 53 Bit Score: 60.11 E-value: 2.01e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11809      3 TAQFDYTGRSERELSFKKGDSLTLYRQVSDDWWRGQLNGQDGLVPHKYITL 53

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 60.39 E-value: 2.09e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1116 CQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGL-FPSNYVK 1168
Cdd:cd11970      4 CAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 57

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 59.61 E-value: 2.57e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIInVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11991      1 EYVAMYTYESNEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKTGVFPSNYVRP 52

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 68.24 E-value: 2.95e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  289 DQRLPEEPVLEDEQQQLEKKLPVtfEDKKRENFERgnlELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKR 368
Cdd:PTZ00121  1126 DARKAEEARKAEDARKAEEARKA--EDAKRVEIAR---KAEDARKAEEARKAEDAKKAEAARKAEEVRKAEELRKAEDAR 1200

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  369 QLELEKQLEKQRELERQREEERrkeierreaaKRELERQRQLEWERNRRQEllnQRNKEQEDIVVLKAKKKTLEFELEAL 448
Cdd:PTZ00121  1201 KAEAARKAEEERKAEEARKAED----------AKKAEAVKKAEEAKKDAEE---AKKAEEERNNEEIRKFEEARMAHFAR 1267

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  449 NDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDSL 528
Cdd:PTZ00121  1268 RQAAIKAEEARKADELKKAEEKKKADEAKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEA 1347

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  529 VTLKRALEAKELARQHLRDQLDEVEK-ETRSKLQEIDIFNNQLKELREIHNKQQLQKQKsmeAERLKQKEQERKIIELEK 607
Cdd:PTZ00121  1348 AKAEAEAAADEAEAAEEKAEAAEKKKeEAKKKADAAKKKAEEKKKADEAKKKAEEDKKK---ADELKKAAAAKKKADEAK 1424

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  608 QKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRLFHQHQEPAKPAVQAPW 687
Cdd:PTZ00121  1425 KKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKKADEAKK 1504


                   ....*
gi 1061899772  688 STAEK 692
Cdd:PTZ00121  1505 AAEAK 1509

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 59.57 E-value: 3.18e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11976      6 YDFCARDRSELSLKEGDIIKILNKKGQQgWWRGEIYGRVGWFPANYVE 53

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 59.22 E-value: 4.14e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1036 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANY 1090
Cdd:cd11883      1 VVVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKVKRGWFPSNY 55

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 58.97 E-value: 4.40e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11840      1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDpDWWRGELNGQTGLFPSNYVEP 53

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 59.22 E-value: 4.43e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQV-----GLFPSNY 1166
Cdd:cd11883      2 VVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSgkvkrGWFPSNY 55

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 59.28 E-value: 4.58e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11901      8 FNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYV 53

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 67.30 E-value: 4.87e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  329 EKRRQALLE------QQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKr 402
Cdd:pfam02463  152 PERRLEIEEeaagsrLKRKKKEALKKLIEETENLAELIIDLEELKLQELKLKEQAKKALEYYQLKEKLELEEEYLLYLD- 230

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  403 elERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEaLNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSREL 482
Cdd:pfam02463  231 --YLKLNEERIDLLQELLRDEQEEIESSKQEIEKEEEKLAQVLK-ENKEEEKEKKLQEEELKLLAKEEEELKSELLKLER 307

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  483 RIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDSLVTLKRALEAK--ELARQHLRDQLDEVEKETRSKL 560
Cdd:pfam02463  308 RKVDDEEKLKESEKEKKKAEKELKKEKEEIEELEKELKELEIKREAEEEEEEELEKlqEKLEQLEEELLAKKKLESERLS 387

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  561 QEIDIFNNQL----KELREIHNKQQLQKQKSMEAERLKQKEqERKIIELEKQKEEAQRRAQERdkqwlEHVQQEDEHQRP 636
Cdd:pfam02463  388 SAAKLKEEELelksEEEKEAQLLLELARQLEDLLKEEKKEE-LEILEEEEESIELKQGKLTEE-----KEELEKQELKLL 461

                          330
                   ....*....|...
gi 1061899772  637 RKLHEEEKLKREE 649
Cdd:pfam02463  462 KDELELKKSEDLL 474

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 58.91 E-value: 5.04e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11786      5 LYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGKQGFFPASYVQ 52

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 58.94 E-value: 5.18e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11806      2 YVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIPASHL 51

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212707 [Multi-domain] Cd Length: 57 Bit Score: 58.97 E-value: 5.50e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWK-------GEVNGQVGLFPSNY 1166
Cdd:cd11773      5 LYDYEPQTEDELTIQEDDILYLLEKSDDDWWKvklkvnsSDDDEPVGLVPATY 57

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 67.30 E-value: 5.77e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  286 TSVDQRLPEEPVLEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQE 365
Cdd:pfam02463  652 VSLEEGLAEKSEVKASLSELTKELLEIQELQEKAESELAKEEILRRQLEIKKKEQREKEELKKLKLEAEELLADRVQEAQ 731

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  366 RKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKE------QEDIVVLKAKKK 439
Cdd:pfam02463  732 DKINEELKLLKQKIDEEEEEEEKSRLKKEEKEEEKSELSLKEKELAEEREKTEKLKVEEEKEeklkaqEEELRALEEELK 811

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  440 TLEFELEALNDKKHQLEGKLQDIRCRlttQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLipEKQILNDQLKQVQ 519
Cdd:pfam02463  812 EEAELLEEEQLLIEQEEKIKEEELEE---LALELKEEQKLEKLAEEELERLEEEITKEELLQELL--LKEEELEEQKLKD 886

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  520 QNSLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELReihnkqqLQKQKSMEAERLKQKEQE 599
Cdd:pfam02463  887 ELESKEEKEKEEKKELEEESQKLNLLEEKENEIEERIKEEAEILLKYEEEPEELL-------LEEADEKEKEENNKEEEE 959

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  600 RKIIELEKQKEEAQRRaqerdkqwlehvqqeDEHQRPRKLHEEEKLKREES 650
Cdd:pfam02463  960 ERNKRLLLAKEELGKV---------------NLMAIEEFEEKEERYNKDEL 995

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 58.65 E-value: 7.07e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE-VNGQVGLFPSNYVKL 1169
Cdd:cd11962      6 YDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGTnSKGESGLFPSNYVEL 54

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 66.62 E-value: 7.51e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  323 RGNLElekRRQALLEQQRKEQERL-AQLERAEqerKERERQEQERKRQLELEKQ--LEKQRELERQREEERRKEIERREA 399
Cdd:TIGR02168  185 RENLD---RLEDILNELERQLKSLeRQAEKAE---RYKELKAELRELELALLVLrlEELREELEELQEELKEAEEELEEL 258

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  400 AKRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQdircRLTTQRQEIESTNKS 479
Cdd:TIGR02168  259 TAELQELEEKLEELRLEVSELEEEIEELQKELYALANEISRLEQQKQILRERLANLERQLE----ELEAQLEELESKLDE 334

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  480 RELRIAEIthlqqqlqesqqmlgrlipEKQIlndQLKQVQQNSLhRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSK 559
Cdd:TIGR02168  335 LAEELAEL-------------------EEKL---EELKEELESL-EAELEELEAELEELESRLEELEEQLETLRSKVAQL 391

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  560 LQEIDIFNNQLKELREihNKQQLQKQKsmeaERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKL 639
Cdd:TIGR02168  392 ELQIASLNNEIERLEA--RLERLEDRR----ERLQQEIEELLKKLEEAELKELQAELEELEEELEELQEELERLEEALEE 465

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  640 HEEEKLKREESVKKKDGEEKGKQEAQDKLGRLFHQHQEPAKpAVQAPWSTAEKGP 694
Cdd:TIGR02168  466 LREELEEAEQALDAAERELAQLQARLDSLERLQENLEGFSE-GVKALLKNQSGLS 519

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 64.94 E-value: 8.06e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  326 LELEKRRQALLEQQRKEQERLAQLER----AEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAK 401
Cdd:pfam13868   28 IAEKKRIKAEEKEEERRLDEMMEEEReralEEEEEKEEERKEERKRYRQELEEQIEEREQKRQEEYEEKLQEREQMDEIV 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  402 RELERQRQLEWERNRRQELLNQRnkEQEDIVVLKAKKKTLEFELEALNDKKhqlegKLQDIRcrlttQRQEIESTNKSRE 481
Cdd:pfam13868  108 ERIQEEDQAEAEEKLEKQRQLRE--EIDEFNEEQAEWKELEKEEEREEDER-----ILEYLK-----EKAEREEEREAER 175

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  482 LRIAEithlqqqlqesqqmlgrlipEKQILNDQL-KQVQQNSLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETRskl 560
Cdd:pfam13868  176 EEIEE--------------------EKEREIARLrAQQEKAQDEKAERDELRAKLYQEEQERKERQKEREEAEKKAR--- 232

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  561 QEIDIFNNQLKELREIHNKQQLQKQKsMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEhvQQEDEHQRPRKLH 640
Cdd:pfam13868  233 QRQELQQAREEQIELKERRLAEEAER-EEEEFERMLRKQAEDEEIEQEEAEKRRMKRLEHRRELE--KQIEEREEQRAAE 309


                   ....*....
gi 1061899772  641 EEEKLKREE 649
Cdd:pfam13868  310 REEELEEGE 318

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 58.09 E-value: 8.32e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11877      1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEgGWWEGTLNGKTGWFPSNYVKE 53

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 58.28 E-value: 8.67e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILV-TKKDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd12046      3 VALFSYEASQPEDLEFQKGDVILVlSKVNEDWLEGQCKGKIGIFPSAFVE 52

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212708 [Multi-domain] Cd Length: 52 Bit Score: 58.25 E-value: 8.97e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDW-WKGEVNGQVGLFPSNYV 1167
Cdd:cd11774      1 QAKALYDYDKQTEEELSFNEGDTLDVYDDSDSDWiLVGFNGTQFGFVPANYI 52

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 58.26 E-value: 9.12e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNY 1166
Cdd:cd11818      5 LYDFTGENEDELSFKAGDIITELESIDEEWMSGELRGKSGIFPKNF 50

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 58.03 E-value: 9.40e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11856      5 IADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLE 52

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 66.11 E-value: 1.02e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLpvTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLE--LEKQ 375
Cdd:COG1196    293 LLAELARLEQDI--ARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEeaLLEA 370

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  376 LEKQRELERQReeerrkeierREAAKRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQL 455
Cdd:COG1196    371 EAELAEAEEEL----------EELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEE 440

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  456 EGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQIlndqLKQVQQNSLHRDSLVTLKRAL 535
Cdd:COG1196    441 EEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLL----LLEAEADYEGFLEGVKAALLL 516

                          250       260
                   ....*....|....*....|..
gi 1061899772  536 EAKELARQHLRDQLDEVEKETR 557
Cdd:COG1196    517 AGLRGLAGAVAVLIGVEAAYEA 538

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 57.87 E-value: 1.12e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNY 1166
Cdd:cd11817      2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGIFPRAF 50

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 57.72 E-value: 1.18e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGE-VNGQVGLFPSNYV 1167
Cdd:cd11763      1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGDgWLEGRnSRGEVGLFPSSYV 53

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 58.12 E-value: 1.21e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV-----NGQVGLFPSNYV 1167
Cdd:cd11887      4 VKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEYvdsngNTKEGIFPKNFV 58

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212702 [Multi-domain] Cd Length: 54 Bit Score: 57.67 E-value: 1.22e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKG-EVNGQVGLFPSNYVK 1168
Cdd:cd11768      1 IVVALYDFQPIEPGDLPLEKGEEYVVLDDSNEHWWRArDKNGNEGYIPSNYVT 53

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 57.69 E-value: 1.32e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVmVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11882      3 RALYACKAEDESELSFEPGQII-TNVQPSDEPGWLEGTLNGRTGLIPENYVE 53

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 57.67 E-value: 1.37e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1122 YDYTAQNDD-ELAFNKGQIINVLNKEDP-----DWWKGEV-NGQVGLFPSNYV 1167
Cdd:cd11771      6 YDFTPENPEmELSLKKGDIVAVLSKTDPlgrdsEWWKGRTrDGRIGWFPSNYV 58

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 57.81 E-value: 1.38e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKD-GDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11827      4 ALYAYDAQDTDELSFNEGDIIEILKEDpSGWWTGRLRGKEGLFPGNYV 51

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 57.52 E-value: 1.42e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKE-DPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11948      1 EAVALYSFQATESDELPFQKGDILKILNMEdDQNWYKAELQGREGYIPKNYIKV 54

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 65.76 E-value: 1.44e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  290 QRLPEEPVLEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKErERQEQERKRQ 369
Cdd:pfam02463  183 ENLAELIIDLEELKLQELKLKEQAKKALEYYQLKEKLELEEEYLLYLDYLKLNEERIDLLQELLRDEQE-EIESSKQEIE 261

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  370 LELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEDIVvlKAKKKTLEFELEALN 449
Cdd:pfam02463  262 KEEEKLAQVLKENKEEEKEKKLQEEELKLLAKEEEELKSELLKLERRKVDDEEKLKESEKEKK--KAEKELKKEKEEIEE 339

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  450 DKKHQLEGKLQDIRCRLTTQRQEiESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDSLV 529
Cdd:pfam02463  340 LEKELKELEIKREAEEEEEEELE-KLQEKLEQLEEELLAKKKLESERLSSAAKLKEEELELKSEEEKEAQLLLELARQLE 418

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  530 TLKRALEAKELArqhlrdQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQ-KQKSMEAERLKQKEQERKIIELEKQ 608
Cdd:pfam02463  419 DLLKEEKKEELE------ILEEEEESIELKQGKLTEEKEELEKQELKLLKDELElKKSEDLLKETQLVKLQEQLELLLSR 492

                          330
                   ....*....|....
gi 1061899772  609 KEEAQRRAQERDKQ 622
Cdd:pfam02463  493 QKLEERSQKESKAR 506

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 57.33 E-value: 1.65e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYVKL 1169
Cdd:cd11789      1 RYRAMYDYAAADDDEVSFQEGDVIINVEIIDDGWMEGTVqrTGQSGMLPANYVEL 55

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 57.39 E-value: 1.75e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11828      2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVRL 53

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 57.03 E-value: 1.92e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11816      6 FDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGIFPLNFV 51

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 57.32 E-value: 2.01e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11902      7 FAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIGWFPSNYV 52

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 56.98 E-value: 2.37e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVL--NKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11836      5 LYAFEARNPDEISFQPGDIIQVDesQVAEPGWLAGELKGKTGWFPANYV 53

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212742 [Multi-domain] Cd Length: 53 Bit Score: 56.72 E-value: 2.56e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11808      2 VVALYDYQEKSPREVSMKKGDILTLLNSSNKDWWKVEVNDRQGFVPAAYVK 52

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 56.73 E-value: 2.80e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKEDpDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11947      4 GKFDFTASGEDELSFKKGDVLKILSSDD-IWFKAELNGEEGYVPKNFV 50

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 56.62 E-value: 3.08e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTK-KDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd12061      4 AKFNFQQTNEDELSFSKGDVIHVTRvEEGGWWEGTHNGRTGWFPSNYVR 52

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 56.88 E-value: 3.11e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVdESQTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11976      3 KARYDFCARDRSELSLKEGDIIKI-LNKKGQQGWWRGEIYGRVGWFPANYVEE 54

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 56.57 E-value: 3.84e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11978      4 IARYDFCARDMRELSLLKGDVVKIYTKMSTNgWWRGEVNGRVGWFPSTYVE 54

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 56.50 E-value: 3.92e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSsDGWWRGECNGQVGWFPSNYV 51

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 56.25 E-value: 4.22e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVL---EQQDMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd11841      1 EVTALYSFEGQQPCDLSFQAGDRITVLtrtDSQFDWWEGRLRGRVGIFPANYVS 54

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 56.14 E-value: 4.35e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKKDG-DWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11996      2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDpDWWQGEINGVTGLFPSNYVKM 54

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 63.97 E-value: 5.03e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  295 EPVLEDEQQQLEK-----KLPVTFEDKKRENFER-------GNLELEKRRQALLEQQRKEQERlAQLERAEQERKERERQ 362
Cdd:pfam05483  362 EELLRTEQQRLEKnedqlKIITMELQKKSSELEEmtkfknnKEVELEELKKILAEDEKLLDEK-KQFEKIAEELKGKEQE 440

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  363 E----QERKRQL-ELEKQLekqreleRQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKE---------- 427
Cdd:pfam05483  441 LifllQAREKEIhDLEIQL-------TAIKTSEEHYLKEVEDLKTELEKEKLKNIELTAHCDKLLLENKEltqeasdmtl 513

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  428 -----QEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIE-STNKSRElriaeitHLQQQLQESQQML 501
Cdd:pfam05483  514 elkkhQEDIINCKKQEERMLKQIENLEEKEMNLRDELESVREEFIQKGDEVKcKLDKSEE-------NARSIEYEVLKKE 586

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  502 GRLIPEKQILNDQLKQVQQNSLHRDSLVTLKRAL------EAKELARQHLRDQLDEVEKE-TRSKLQEI-DIFNNQL--K 571
Cdd:pfam05483  587 KQMKILENKCNNLKKQIENKNKNIEELHQENKALkkkgsaENKQLNAYEIKVNKLELELAsAKQKFEEIiDNYQKEIedK 666

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  572 ELREIHNKQQLQKQKSMEAERLK-QKEQER----KIIE----LEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEE 642
Cdd:pfam05483  667 KISEEKLLEEVEKAKAIADEAVKlQKEIDKrcqhKIAEmvalMEKHKHQYDKIIEERDSELGLYKNKEQEQSSAKAALEI 746

                          410       420
                   ....*....|....*....|....*...
gi 1061899772  643 EKLKREESVKKKDGEEKGKQEAQDKLGR 670
Cdd:pfam05483  747 ELSNIKAELLSLKKQLEIEKEEKEKLKM 774

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 56.17 E-value: 5.17e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11920      6 VYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGIFPISYVE 53

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 55.98 E-value: 5.21e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGE-VQGQKGWFPKSYV 924
Cdd:cd11812      4 ALYDYTANRSDELTIHRGDIIRVLYKdNDNWWFGSlVNGQQGYFPANYV 52

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 56.12 E-value: 5.30e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd11873      1 EVIVEFDYDAEEPDELTLKVGDIITnVKKMEEGWWEGTLNGKRGMFPDNFVK 52

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 55.97 E-value: 5.33e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11813      1 RAKALLDFERHDDDELGFRKNDIITIISQKDeHCWVGELNGLRGWFPAKFVEL 53

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 56.04 E-value: 5.92e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11815      5 LHDFPAEHSDDLSLNSGEIVYLLEKIDTEWYRGKCKNTTGIFPANHVK 52

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 56.06 E-value: 6.13e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd12057      1 YCKVLFPYEAQNEDELTIKEGDIVTLISKDCIDAGWWEGELNGRRGVFPDNFVK 54

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 55.81 E-value: 6.62e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11823      4 ALYSYTANREDELSLQPGDIIEVHEKQDDgWWLGELNGKKGIFPATYV 51

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 55.29 E-value: 8.10e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQ-GQKGWFP 920
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSeDGWWKGRNKgGKEGLIP 46

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 55.46 E-value: 8.36e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11807      2 VVYALFDYEAENGDELSFREGDELTVLRKGDDDeteWWWARLNDKEGYVPRNLLGL 57

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212942 [Multi-domain] Cd Length: 54 Bit Score: 55.21 E-value: 9.31e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLnKEDPDWW--KGEVNGQVGLFPSNYV 1167
Cdd:cd12009      2 VIAQYDFVPSNERDLQLKKGEKLQVL-KSDGEWWlaKSLTTGKEGYIPSNYV 52

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 55.11 E-value: 9.91e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11838      3 IALYPYESNEPGDLTFNAGDVILVTKKDGEWWTGTIGDRTGIFPSNYVRP 52

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212939 [Multi-domain] Cd Length: 56 Bit Score: 55.44 E-value: 1.00e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYV 1167
Cdd:cd12006      4 VALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARslTTGETGYIPSNYV 54

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 55.02 E-value: 1.03e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  704 KVVyyrALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11826      1 KVV---ALYDYTADKDDELSFQEGDIIYV--TKKNDDGWYEGVLNGVTGLFPGNYVE 52

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 55.20 E-value: 1.06e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11833      3 VALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIEDRVGFFPANFV 51

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 54.96 E-value: 1.15e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11995      2 QVIGMYDYTAQNDDELAFSKGQIInVLNKEDPDWWKGELNGQVGLFPSNYVKL 54

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212709 [Multi-domain] Cd Length: 57 Bit Score: 55.02 E-value: 1.19e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDP-DWWKGE--VNGQVGLFPSNYVKL 1169
Cdd:cd11775      6 LYDFDAQSDDELTVKEGDVVYILDDKKSkDWWMVEnvSTGKEGVVPASYIEI 57

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 55.01 E-value: 1.22e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEV-QGQKGWFPKSYVKL 926
Cdd:cd11819      1 RAKALYDYQAAEDNEISFVEGDIITQIEQIDEgWWLGVNaKGQKGLFPANYVEL 54

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 55.04 E-value: 1.23e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1042 SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYV 1091
Cdd:cd11823      7 SYTANREDELSLQPGDIIEVHEKQDDGWWLGEL--NGKK---GIFPATYV 51

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 54.82 E-value: 1.26e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTK-KDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11833      2 YVALYKFKPQENEDLEMRPGDKITLLDdSNEDWWKGKIEDRVGFFPANFV 51

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 54.54 E-value: 1.32e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVK 925
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEEsEDGWWEGINTGRTGLVPANYVE 49

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 54.91 E-value: 1.45e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKLI 927
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKdNDGWWEGETGGRVGLVPSTAVEEI 54

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 54.56 E-value: 1.51e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 925
Cdd:cd11805      1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPdWWKGELRGRVGIFPANYVQ 52

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 54.43 E-value: 1.56e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGGELKGKTGWFPANY 758
Cdd:cd11778      1 YVEALYDYEAQGDDEISIRVGDRIAVIRGDDGS-GWTYGEINGVKGLFPTSY 51

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212930 [Multi-domain] Cd Length: 56 Bit Score: 54.58 E-value: 1.64e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEV-NGQVGLFPSNYVK 1168
Cdd:cd11997      3 RVRALYDYTGQEADELSFKAGEELLKIGEEDEQgWCKGRLlSGRIGLYPANYVE 56

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212703 [Multi-domain] Cd Length: 57 Bit Score: 54.62 E-value: 1.70e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLN-KEDPDWWKGE-VNGQVGLFPSNYVK 1168
Cdd:cd11769      3 ECIAKYNFNGASEEDLPFKKGDILTIVAvTKDPNWYKAKnKDGREGMIPANYVQ 56

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 54.41 E-value: 1.83e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNY 1012
Cdd:cd11817      3 VALYDFTGETEEDLSFQRGDRILVTEHlDAEWSRGRLNGREGIFPRAF 50

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 54.61 E-value: 1.84e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYVKL 1169
Cdd:cd11916      6 ALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSrrTKQFGTFPGNYVKL 57

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 61.96 E-value: 1.87e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLpvtfEDKKRENFERGNlELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKrqlELEKQLE 377
Cdd:TIGR04523  340 LNEQISQLKKEL----TNSESENSEKQR-ELEEKQNEIEKLKKENQSYKQEIKNLESQINDLESKIQNQE---KLNQQKD 411

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  378 KQRELERQReeerrkeierreaaKRELERQRQlewernrrqELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEG 457
Cdd:TIGR04523  412 EQIKKLQQE--------------KELLEKEIE---------RLKETIIKNNSEIKDLTNQDSVKELIIKNLDNTRESLET 468

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  458 KLQDIRCRLTTQRQEIESTNKSRELRIAEIThlqqqlqesqqmlgRLIPEKQILNDQLKQVQQNSlhrDSLVTLKRALEA 537
Cdd:TIGR04523  469 QLKVLSRSINKIKQNLEQKQKELKSKEKELK--------------KLNEEKKELEEKVKDLTKKI---SSLKEKIEKLES 531

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  538 ----KELARQHLRDQLDEVEKE-TRSKLQ-EIDIFNNQLKELReiHNKQQLQKQKSMEAERLKQKEQERKiiELEKQKEE 611
Cdd:TIGR04523  532 ekkeKESKISDLEDELNKDDFElKKENLEkEIDEKNKEIEELK--QTQKSLKKKQEEKQELIDQKEKEKK--DLIKEIEE 607

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  612 AQRRAQERDKQwLEHVQQEDEhqrprKLHEEEKlkreesvkkkdgeekGKQEAQDKLGRLFHQHQEPAKPAV 683
Cdd:TIGR04523  608 KEKKISSLEKE-LEKAKKENE-----KLSSIIK---------------NIKSKKNKLKQEVKQIKETIKEIR 658

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 54.46 E-value: 2.03e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 925
Cdd:cd11949      2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPnWWKGACHGQTGMFPRNYVT 52

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 54.46 E-value: 2.11e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQII-NVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12053      1 EYIVEYDYDAVHEDELTIRVGEIIrNVKKLEEEGWLEGELNGRRGMFPDNFVK 53

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212725 [Multi-domain] Cd Length: 59 Bit Score: 54.61 E-value: 2.14e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESQTGEP--GWLGG--ELKGKTGWFPANYAEK 761
Cdd:cd11791      2 LRVLYPYTPQEEDELELVPGDYIYVSPEELDSSsdGWVEGtsWLTGCSGLLPENYTEK 59

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 54.29 E-value: 2.35e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 925
Cdd:cd11786      2 AKALYNYEGKEPGDLSFKKGDIILLRKRIDEnWYHGECNGKQGFFPASYVQ 52

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 61.62 E-value: 2.72e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  339 QRKEQERLAQL-ERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRkeierreaakRELER-QRQLEWERNR 416
Cdd:TIGR02169  669 SRSEPAELQRLrERLEGLKRELSSLQSELRRIENRLDELSQELSDASRKIGEIE----------KEIEQlEQEEEKLKER 738

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  417 RQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQR--------QEIESTNKSRELRIAEIT 488
Cdd:TIGR02169  739 LEELEEDLSSLEQEIENVKSELKELEARIEELEEDLHKLEEALNDLEARLSHSRipeiqaelSKLEEEVSRIEARLREIE 818

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  489 HLQQQLQESQQMLGRLIPEKQILNDQLKQvQQNSLHR--DSLVTLKRALEA----KELARQHLRDQLDEVEKET---RSK 559
Cdd:TIGR02169  819 QKLNRLTLEKEYLEKEIQELQEQRIDLKE-QIKSIEKeiENLNGKKEELEEeleeLEAALRDLESRLGDLKKERdelEAQ 897

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  560 LQEIDIFNNQLKELREIHNKQ--QLQKQKSMEAERLKQKEQERKIIELEKQKE------EAQRRAQERDKQWLEHV---- 627
Cdd:TIGR02169  898 LRELERKIEELEAQIEKKRKRlsELKAKLEALEEELSEIEDPKGEDEEIPEEElsledvQAELQRVEEEIRALEPVnmla 977

                          330       340
                   ....*....|....*....|....
gi 1061899772  628 -QQEDEHQRPRKLHEE--EKLKRE 648
Cdd:TIGR02169  978 iQEYEEVLKRLDELKEkrAKLEEE 1001

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 53.86 E-value: 2.73e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKeDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11992      1 EYIALYPYSSSEPGDLTFNEGEEILVTQK-DGEWWTGSIEDRTGIFPSNYVR 51

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 54.18 E-value: 2.74e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11964      5 AIYDFEAAEDNELTFKAGDIItILDDSDPNWWKGETPQGTGLFPSNFV 52

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 53.92 E-value: 2.78e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANYAEKI 762
Cdd:cd12061      3 RAKFNFQQTNEDELSFSKGDVIHVTRVEEG--GWWEGTHNGRTGWFPSNYVREI 54

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 53.96 E-value: 3.04e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMV---DESqtgepGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11827      3 KALYAYDAQDTDELSFNEGDIIEIlkeDPS-----GWWTGRLRGKEGLFPGNYVEK 53

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 53.84 E-value: 3.11e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKG--EVNGQVGLFPSNYVK 1168
Cdd:cd11780      5 LYSYTPQNEDELELREGDIVYVMEKCDDGWFVGtsERTGLFGTFPGNYVA 54

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 53.88 E-value: 3.16e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYV 1167
Cdd:cd11793      1 QVQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGErlRDGERGWFPSSYT 53

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 53.80 E-value: 3.26e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11995      2 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPdWWKGELNGQVGLFPSNYVKL 54

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 53.89 E-value: 3.38e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGD-----KAGVFPSNYV 1013
Cdd:cd11887      5 KALYPYESDHEDDLNFDVGQLITVTEEeDADWYFGEYVDsngntKEGIFPKNFV 58

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 53.85 E-value: 3.40e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTK-KDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd12060      6 ARFNFKQTNEDELSVCKGDIIYVTRvEEGGWWEGTLNGKTGWFPSNYVR 54

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 53.81 E-value: 3.48e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1036 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYV 1091
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNG-----QVGWFPSNYV 51

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 53.89 E-value: 3.55e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKDGD---WWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11875      4 VLFDYEAENEDELTLREGDIVTILSKDCEdkgWWKGELNGKRGVFPDNFVEP 55

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 53.50 E-value: 3.68e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKL 926
Cdd:cd11781      2 ARALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYeGEHNGRVGIFPASYVEI 53

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 53.51 E-value: 3.69e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772 1124 YTAQNDDELAFNKGQIINVLNKEDpDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11990      8 WTAKKDNHLNFSKNDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKL 52

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 53.41 E-value: 3.89e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGD-VILVTKKDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd11985      2 YVALYKFLPQENNDLPLQPGDrVMVVDDSNEDWWKGKSGDRVGFFPANFVQ 52

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 53.48 E-value: 4.37e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVL--EQQDMWWFGE--VQGQKGWFPKSYVK 925
Cdd:cd11779      2 RVKALYPHAAGGETQLSFEEGDVITLLgpEPRDGWHYGEneRSGRRGWFPIAYTE 56

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212940 [Multi-domain] Cd Length: 58 Bit Score: 53.50 E-value: 4.55e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYV 1167
Cdd:cd12007      4 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsiATGKNGYIPSNYV 54

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 53.00 E-value: 4.72e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEEsEDGWWEGINTGRTGLVPANYVE 49

Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) proteins; The MPP/p55 subfamily of MAGUK (membrane-associated guanylate kinase) proteins includes at least eight vertebrate members (MPP1-7 and CASK), four Drosophila proteins (Stardust, Varicose, CASK and Skiff), and other similar proteins; they all contain one each of the core of three domains characteristic of MAGUK proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, most members except for MPP1 contain N-terminal L27 domains and some also contain a Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. CASK has an additional calmodulin-dependent kinase (CaMK)-like domain at the N-terminus. Members of this subfamily are scaffolding proteins that play important roles in regulating and establishing cell polarity, cell adhesion, and synaptic targeting and transmission, among others. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212796 Cd Length: 61 Bit Score: 53.35 E-value: 4.81e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1121 MYDYTAQNDDE-------LAFNKGQIINVLNKEDPDWWK----GEVNGQVGLFPS 1164
Cdd:cd11862      5 LFDYDPEEDPLipckeagLSFKKGDILQIVNQDDPNWWQarkvGDPNGRAGLIPS 59

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 53.19 E-value: 4.86e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11840      3 IALFPYTAQNEDELSFQKGDIINVLSKD--DPDWWRGELNGQTGLFPSNYVE 52

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 53.30 E-value: 4.93e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLE-QQDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11961      2 AKALYDYDAAEDNELSFFENDKIINIEfVDDDWWLGECHGSRGLFPSNYVEL 53

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 53.24 E-value: 5.14e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQARgkkrqIGWFPANYV 1091
Cdd:cd12142      3 RVLFDYNPVAPDELALKKGDVIEVISKETEdeGWWEGELNGR-----RGFFPDNFV 53

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 53.42 E-value: 5.17e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 927
Cdd:cd11803      2 CCRALYDFEPENEGELGFKEGDIITLTNQIDENWYeGMVNGQSGFFPVNYVEVL 55

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 53.30 E-value: 5.47e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11870      1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDGRVGIFPKCFVV 52

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 60.93 E-value: 5.57e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  294 EEPVLEDEQQQLEKKLPVTFEDKKRENFERGnlelEKRRQALLEQQRKEQERLAQLERAEQERK-------ERERQEQER 366
Cdd:PTZ00121  1500 DEAKKAAEAKKKADEAKKAEEAKKADEAKKA----EEAKKADEAKKAEEKKKADELKKAEELKKaeekkkaEEAKKAEED 1575

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  367 K----RQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQR--QLEWERNRRQELLNQRNKEQEDivvlKAKKKT 440
Cdd:PTZ00121  1576 KnmalRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKaeELKKAEEEKKKVEQLKKKEAEE----KKKAEE 1651

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  441 LEFELEALNDKKHQLegklqdircrlttQRQEIESTNKSRELRIAEithlqqqlqesqqmlgrlipekqilNDQLKQVQQ 520
Cdd:PTZ00121  1652 LKKAEEENKIKAAEE-------------AKKAEEDKKKAEEAKKAE-------------------------EDEKKAAEA 1693

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  521 nslhrdslvtLKRALEAKELARQHLRDQLDEVEK-ETRSKLQEIdifnNQLKeLREIHNKQQLQKQKsmeAERLKQKEQE 599
Cdd:PTZ00121  1694 ----------LKKEAEEAKKAEELKKKEAEEKKKaEELKKAEEE----NKIK-AEEAKKEAEEDKKK---AEEAKKDEEE 1755

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  600 RKIIELEKQKEEAQRRAQERDKQWL--EHVQQEDEhqrPRKLHEEEKLK 646
Cdd:PTZ00121  1756 KKKIAHLKKEEEKKAEEIRKEKEAVieEELDEEDE---KRRMEVDKKIK 1801

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 53.14 E-value: 5.95e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKED----PDWWKGEVNGQVGLFPSNY 1166
Cdd:cd11800      1 YYYALYTFEARSPGELSVTEGQVVTVLEKHDlkgnPEWWLVEDRGKQGYVPSNY 54

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 53.02 E-value: 5.96e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMV---DESQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd12058      2 WTALYDYEASGEDELSLRRGDVVEVlsqDAAVSGDDGWWAGKIRHRLGIFPANY 55

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 53.09 E-value: 6.10e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTV---GdKAGVFPSNYVRL 1015
Cdd:cd11789      2 YRAMYDYAAADDDEVSFQEGDVIInVEIIDDGWMEGTVqrtG-QSGMLPANYVEL 55

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 53.02 E-value: 6.23e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKE----DPDWWKGEVNGQ-VGLFPSNYVKL 1169
Cdd:cd11864      3 RAEYDFVAESEDELSFRAGDKLRLAPKElqprVRGWLLATVDGQkIGLVPANYVKI 58

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212980 Cd Length: 53 Bit Score: 52.90 E-value: 6.48e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd12047      1 RMVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDGRIGIFPKCFA 51

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 52.91 E-value: 6.61e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11961      4 ALYDYDAAEDNELSFFENDKIInIEFVDDDWWLGECHGSRGLFPSNYVEL 53

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 52.63 E-value: 7.58e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11929      6 LCNYRGHNPGDLKFNKGDVILLRRQLDENWYLGEINGVSGIFPASSVEV 54

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 52.90 E-value: 7.88e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKD-GD--WWTGTVGDKAGVFPSNYV 1013
Cdd:cd12056      6 ALFHYEGTNEDELDFKEGEIILIISKDtGEpgWWKGELNGKEGVFPDNFV 55

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 60.08 E-value: 8.30e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  297 VLEDEQQQLEKKLpvtfEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLEraeQERKERerqeqeRKRQLELEKQL 376
Cdd:PRK03918   369 AKKEELERLKKRL----TGLTPEKLEKELEELEKAKEEIEEEISKITARIGELK---KEIKEL------KKAIEELKKAK 435

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  377 EKqrelerqreeerrkeierREAAKRELERQrqlewernRRQELLNQRNKEQEDIvvlKAKKKTLEFELEALNDKKHQLE 456
Cdd:PRK03918   436 GK------------------CPVCGRELTEE--------HRKELLEEYTAELKRI---EKELKEIEEKERKLRKELRELE 486

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  457 GKLQDIRcRLTTQRQ---EIEST-NKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQnslhrdslvtLK 532
Cdd:PRK03918   487 KVLKKES-ELIKLKElaeQLKELeEKLKKYNLEELEKKAEEYEKLKEKLIKLKGEIKSLKKELEKLEE----------LK 555

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  533 RALEAKELARQHLRDQLDEVEKETRSK-LQEIDIFNNQLKELREIHNK--------QQLQ-KQKSMEAERLKQKEQERKI 602
Cdd:PRK03918   556 KKLAELEKKLDELEEELAELLKELEELgFESVEELEERLKELEPFYNEylelkdaeKELErEEKELKKLEEELDKAFEEL 635

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772  603 IELEKQKEEAQRRAQErdkqwLEHVQQEDEHQRPRKLHEEekLKRE 648
Cdd:PRK03918   636 AETEKRLEELRKELEE-----LEKKYSEEEYEELREEYLE--LSRE 674

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 59.99 E-value: 8.63e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  338 QQRKEQERL--------AQLERAEQERKERERQEQERKRQLELEKqlekqrelerqreeerrkeierreaakRELERQRQ 409
Cdd:pfam02463  148 AMMKPERRLeieeeaagSRLKRKKKEALKKLIEETENLAELIIDL---------------------------EELKLQEL 200

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  410 LEwERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLegklqdircrLTTQRQEIESTNKSRELRIAEITH 489
Cdd:pfam02463  201 KL-KEQAKKALEYYQLKEKLELEEEYLLYLDYLKLNEERIDLLQEL----------LRDEQEEIESSKQEIEKEEEKLAQ 269

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  490 LQQQLQESQQmlgrlipEKQILNDQLKQVQQNSLhrdslvTLKRALEAKELARQHLRDQLDEVEKETRSKLQEID---IF 566
Cdd:pfam02463  270 VLKENKEEEK-------EKKLQEEELKLLAKEEE------ELKSELLKLERRKVDDEEKLKESEKEKKKAEKELKkekEE 336

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  567 NNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQ-WLEH---------VQQEDEHQRP 636
Cdd:pfam02463  337 IEELEKELKELEIKREAEEEEEEELEKLQEKLEQLEEELLAKKKLESERLSSAAKLkEEELelkseeekeAQLLLELARQ 416

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  637 RKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRLFHQHQEPAKPAVQAPWSTAEKG-PLTISAQENVKVVYYRALYPFE 715
Cdd:pfam02463  417 LEDLLKEEKKEELEILEEEEESIELKQGKLTEEKEELEKQELKLLKDELELKKSEDLlKETQLVKLQEQLELLLSRQKLE 496

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  716 SRSHDEITIQPGDIVMVDESQTGEPGWLGGE--LKGKTGWFPANYAEKIPENEVPAPVKPVTDSTSAPAPKLALRETPAP 793
Cdd:pfam02463  497 ERSQKESKARSGLKVLLALIKDGVGGRIISAhgRLGDLGVAVENYKVAISTAVIVEVSATADEVEERQKLVRALTELPLG 576

                          490
                   ....*....|....*....
gi 1061899772  794 LAVTSSEPSTTPNNWADFS 812
Cdd:pfam02463  577 ARKLRLLIPKLKLPLKSIA 595

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 52.64 E-value: 8.64e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKD----GD--WWTGTVGDKAGVFPSNYV 1013
Cdd:cd12058      4 ALYDYEASGEDELSLRRGDVVEVLSQDaavsGDdgWWAGKIRHRLGIFPANYV 56

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 52.78 E-value: 9.17e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKDGD-----WWTGTVGDKAGVFPS 1010
Cdd:cd11762      4 ALYDYEAQSDEELSFPEGAIIRILRKDDNgvddgWWEGEFNGRVGVFPS 52

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 52.70 E-value: 9.31e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQ---VGLFPSNYVKL 1169
Cdd:cd11965      1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFVHI 56

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 52.32 E-value: 9.45e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGD-KAGVFPSNYVRL 1015
Cdd:cd11819      3 KALYDYQAAEDNEISFVEGDIITqIEQIDEGWWLGVNAKgQKGLFPANYVEL 54

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 52.33 E-value: 9.61e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11763      1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGDGWLEGRNSRGEVGLFPSSYVE 54

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 52.29 E-value: 9.98e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11996      2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDPdWWQGEINGVTGLFPSNYVKM 54

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 52.43 E-value: 1.01e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11866      4 GLWDCSGNEPDELSFKRGDLIYIISKEydSFGWWVGELNGKVGLVPKDYL 53

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 52.42 E-value: 1.02e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTgEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11843      3 RALYDYEGQESDELSFKAGDILTKLEEED-EQGWCKGRLDGRVGLYPANYVE 53

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 52.26 E-value: 1.04e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11927      5 ALYNYEGKEPGDLKFSKGDIIILRRQvDENWYHGEVNGIHGFFPTNFVQI 54

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 52.70 E-value: 1.05e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANYAEKI 762
Cdd:cd12060      5 KARFNFKQTNEDELSVCKGDIIYVTRVEEG--GWWEGTLNGKTGWFPSNYVREI 56

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 52.42 E-value: 1.05e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11959      2 AVALYDYQAADDDEISFDPDDIITNIEMIDEgWWRGVCRGKYGLFPANYVEL 53

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 52.42 E-value: 1.06e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  710 ALYPFESRSHDEITIQPGDIV----MVDEsqtgepGWLGGELKGKTGWFPANYAE 760
Cdd:cd11959      4 ALYDYQAADDDEISFDPDDIItnieMIDE------GWWRGVCRGKYGLFPANYVE 52

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 52.33 E-value: 1.11e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILV-TKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11963      6 ALYDFEAVEDNELTFKHGEIIIVlDDSDANWWKGENHRGVGLFPSNFV 53

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 52.36 E-value: 1.13e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQDM---WWFGEVQGQKGWFPKSYV 924
Cdd:cd11836      3 RALYAFEARNPDEISFQPGDIIQVDESQVAepgWLAGELKGKTGWFPANYV 53

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 51.82 E-value: 1.14e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVT-KKDGDWWTGTV-GDKAGVFPS 1010
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLeKSEDGWWKGRNkGGKEGLIPS 47

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 52.27 E-value: 1.15e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVmVDESQTgEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11873      2 VIVEFDYDAEEPDELTLKVGDII-TNVKKM-EEGWWEGTLNGKRGMFPDNFVKV 53

Second Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212945 Cd Length: 62 Bit Score: 52.29 E-value: 1.18e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772 1119 IGMYDYTAQ----NDD----ELAFNKGQIINVLNKEDPD-WWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12012      3 VALFDYDPLtmspNPDaaeeELPFKEGQLIKVYGDKDADgFYLGEINGRRGLVPCNMVS 61

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 52.21 E-value: 1.22e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGElqaRGKKRqiGWFPANYVKLL 1094
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGE---TGGRV--GLVPSTAVEEI 54

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 51.97 E-value: 1.24e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772 1123 DYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11796      7 DLSAQLDEELDLREGDVVTITGILDKGWFRGELNGRRGIFPEGFV 51

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 52.22 E-value: 1.28e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTK-KDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11986      2 FVALYRFKALEKDDLDFHPGERITVIDdSNEEWWRGKIGEKTGYFPMNFI 51

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 52.10 E-value: 1.35e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANY 758
Cdd:cd11818      3 RALYDFTGENEDELSFKAGDIITELESIDEE--WMSGELRGKSGIFPKNF 50

Caldesmon;

Pssm-ID: 460421 [Multi-domain] Cd Length: 495 Bit Score: 58.73 E-value: 1.35e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  350 ERAEQERKERERQEQERKRQLE--------LEKQLEKQRELERQREEERRKEIERREAA------KRELERQRQLEWERN 415
Cdd:pfam02029    5 EEAARERRRRAREERRRQKEEEepsgqvteSVEPNEHNSYEEDSELKPSGQGGLDEEEAfldrtaKREERRQKRLQEALE 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  416 RRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKL----------QDIRCRLTTQRQEIESTNKSRELRIA 485
Cdd:pfam02029   85 RQKEFDPTIADEKESVAERKENNEEEENSSWEKEEKRDSRLGRYkeeeteirekEYQENKWSTEVRQAEEEGEEEEDKSE 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  486 EITHLQQQLQESQQMLGRLIPE--------KQILNDQLKQVQQNSLHRDSLVTlkrALEAKELARQHLRDQLDEVEKETR 557
Cdd:pfam02029  165 EAEEVPTENFAKEEVKDEKIKKekkvkyesKVFLDQKRGHPEVKSQNGEEEVT---KLKVTTKRRQGGLSQSQEREEEAE 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  558 SKLQEidifNNQLKELReihnkQQLQKQKSMEAERLKQKEQERkIIELE--KQKEEAQRRAQErdkqwlehvqqedEHQR 635
Cdd:pfam02029  242 VFLEA----EQKLEELR-----RRRQEKESEEFEKLRQKQQEA-ELELEelKKKREERRKLLE-------------EEEQ 298

                          330
                   ....*....|....
gi 1061899772  636 PRKLHEEEKLKREE 649
Cdd:pfam02029  299 RRKQEEAERKLREE 312

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 52.23 E-value: 1.37e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11928      5 ALYSYEGKEPGDLKFNKGDIIILRRKvDENWYHGELNGCHGFLPASYIQC 54

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 51.95 E-value: 1.39e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQK-GWFPKSYVK 925
Cdd:cd11825      2 VKALYDYRAQRPDELSFCKHAIITNVEKEDgGWWRGDYGGKKqKWFPANYVE 53

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 51.95 E-value: 1.47e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKrqiGWFPANYV 1091
Cdd:cd11793      2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGERLRDGER---GWFPSSYT 53

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 59.31 E-value: 1.49e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  294 EEPVLEDEQQQLEKKLPVTfeDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERA------EQERKERERQEQERK 367
Cdd:TIGR02169  731 EEEKLKERLEELEEDLSSL--EQEIENVKSELKELEARIEELEEDLHKLEEALNDLEARlshsriPEIQAELSKLEEEVS 808

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  368 RQLELEKQLEKQRElerqreeerrkeierreaaKRELERQrQLEWERN----RRQELLNQRNKEQEDIVVLKAKKKTLEF 443
Cdd:TIGR02169  809 RIEARLREIEQKLN-------------------RLTLEKE-YLEKEIQelqeQRIDLKEQIKSIEKEIENLNGKKEELEE 868

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  444 ELEALNDKKHQLEGKLQDIRcrltTQRQEIESTNKSRELRIAEIthlQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSL 523
Cdd:TIGR02169  869 ELEELEAALRDLESRLGDLK----KERDELEAQLRELERKIEEL---EAQIEKKRKRLSELKAKLEALEEELSEIEDPKG 941

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  524 HRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREihnkqqlqKQKSMEAERlkqKEQERKII 603
Cdd:TIGR02169  942 EDEEIPEEELSLEDVQAELQRVEEEIRALEPVNMLAIQEYEEVLKRLDELKE--------KRAKLEEER---KAILERIE 1010

                          330
                   ....*....|...
gi 1061899772  604 ELEKQKEEAQRRA 616
Cdd:TIGR02169 1011 EYEKKKREVFMEA 1023

Caldesmon;

Pssm-ID: 460421 [Multi-domain] Cd Length: 495 Bit Score: 58.73 E-value: 1.52e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  342 EQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERRE---------AAKRELERQRQLEW 412
Cdd:pfam02029    2 EDEEEAARERRRRAREERRRQKEEEEPSGQVTESVEPNEHNSYEEDSELKPSGQGGLdeeeafldrTAKREERRQKRLQE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  413 ERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKL----------QDIRCRLTTQRQEIESTNKSREL 482
Cdd:pfam02029   82 ALERQKEFDPTIADEKESVAERKENNEEEENSSWEKEEKRDSRLGRYkeeeteirekEYQENKWSTEVRQAEEEGEEEED 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  483 RIAEITHLQQQLQESQQMLGRLIPE--------KQILNDQLKQVQQNSLHRDSLVTlkrALEAKELARQHLRDQLDEVEK 554
Cdd:pfam02029  162 KSEEAEEVPTENFAKEEVKDEKIKKekkvkyesKVFLDQKRGHPEVKSQNGEEEVT---KLKVTTKRRQGGLSQSQEREE 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  555 ETRSKLQEidifNNQLKELReihnkQQLQKQKSMEAERLKQKEQERkIIELE--KQKEEAQRRAQERDKQwlehvQQEDE 632
Cdd:pfam02029  239 EAEVFLEA----EQKLEELR-----RRRQEKESEEFEKLRQKQQEA-ELELEelKKKREERRKLLEEEEQ-----RRKQE 303

                          330
                   ....*....|....*..
gi 1061899772  633 HQRPRKLHEEEKLKREE 649
Cdd:pfam02029  304 EAERKLREEEEKRRMKE 320

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 58.81 E-value: 1.59e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  293 PEEPV-LEDEQQQLEKKLPVTFEDKKRENFERGN---LELEKRRQALLEQQRKEQErlaQLERAEQERKERERQEQERKR 368
Cdd:pfam15709  311 SEEERsEEDPSKALLEKREQEKASRDRLRAERAEmrrLEVERKRREQEEQRRLQQE---QLERAEKMREELELEQQRRFE 387

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  369 QLELEKQlekQRELERQREEERRKEIERREAAKRELERQRQLEWERnRRQELlnQRNKEQEDIVVLKAKKKTL-EFELEA 447
Cdd:pfam15709  388 EIRLRKQ---RLEEERQRQEEEERKQRLQLQAAQERARQQQEEFRR-KLQEL--QRKKQQEEAERAEAEKQRQkELEMQL 461

                          170       180       190
                   ....*....|....*....|....*....|...
gi 1061899772  448 LNDKKHQLEGKLQDircRLTTQRQEIESTNKSR 480
Cdd:pfam15709  462 AEEQKRLMEMAEEE---RLEYQRQKQEAEEKAR 491

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 51.90 E-value: 1.62e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEV-----QGQKGWFPKSY 923
Cdd:cd11883      3 VALYDFTPKSKNQLSFKAGDIIYVLNKDPSgWWDGVIisssgKVKRGWFPSNY 55

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 51.88 E-value: 1.63e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYVK 1092
Cdd:cd11873      4 VEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTL--NGKR---GMFPDNFVK 52

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 51.61 E-value: 1.71e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11828      2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKdWWWGSIRDEEGWFPASFVRL 53

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 58.83 E-value: 1.75e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  301 EQQQLEKKLPVTFEDKKRENFER--GNLELEKRRQALLEQQRKE-----QERLAQLERAEQERKERERQEQERKRQLELE 373
Cdd:TIGR00618  268 RIEELRAQEAVLEETQERINRARkaAPLAAHIKAVTQIEQQAQRihtelQSKMRSRAKLLMKRAAHVKQQSSIEEQRRLL 347

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  374 KQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKH 453
Cdd:TIGR00618  348 QTLHSQEIHIRDAHEVATSIREISCQQHTLTQHIHTLQQQKTTLTQKLQSLCKELDILQREQATIDTRTSAFRDLQGQLA 427

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  454 QLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGrlipEKQILNDQLKQVQQNSLHR-DSLVTLK 532
Cdd:TIGR00618  428 HAKKQQELQQRYAELCAAAITCTAQCEKLEKIHLQESAQSLKEREQQLQ----TKEQIHLQETRKKAVVLARlLELQEEP 503

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  533 RALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREI-HNKQQLQKQksmeAERLKQKEQErkiielEKQKEE 611
Cdd:TIGR00618  504 CPLCGSCIHPNPARQDIDNPGPLTRRMQRGEQTYAQLETSEEDVyHQLTSERKQ----RASLKEQMQE------IQQSFS 573

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  612 AQRRAQERDKQWLEHVQQEDEHQRP--RKLHEEEKLKREESvkkkDGEEKGKQEAQDKLGRLFHQHQ 676
Cdd:TIGR00618  574 ILTQCDNRSKEDIPNLQNITVRLQDltEKLSEAEDMLACEQ----HALLRKLQPEQDLQDVRLHLQQ 636

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 51.73 E-value: 1.76e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1123 DYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11813      7 DFERHDDDELGFRKNDIITIISQKDEHCWVGELNGLRGWFPAKFVEL 53

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 51.86 E-value: 1.76e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVdESQTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11830      4 ARYDFCARDMRELSLKEGDVVKI-YNKKGQQGWWRGEINGRIGWFPSTYVEE 54

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 51.64 E-value: 1.82e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPdWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11989      1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 52

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212828 Cd Length: 58 Bit Score: 51.89 E-value: 1.86e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKE----DPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11895      4 ALYSYTGQSPEELSFPEGALIRLLPRAqdgvDDGFWRGEFGGRVGVFPSLLVE 56

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 51.44 E-value: 1.86e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKKD-GDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDnDGWWEGETGGRVGLVPSTAVEE 53

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 51.82 E-value: 1.89e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  968 MYTYESSEQGDLTFQQGDVILVTKK---DGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd12057      5 LFPYEAQNEDELTIKEGDIVTLISKdciDAGWWEGELNGRRGVFPDNFVKL 55

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 51.49 E-value: 1.90e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11803      5 ALYDFEPENEGELGFKEGDIItLTNQIDENWYEGMVNGQSGFFPVNYV 52

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 51.56 E-value: 2.06e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKE---DPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11884      2 VVAVRAYITRDQTLLSFHKGDVIKLLPKEgplDPGWLFGTLDGRSGAFPKEYV 54

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 51.05 E-value: 2.15e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELK-GKTGWFPA 756
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKS--EDGWWKGRNKgGKEGLIPS 47

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 51.69 E-value: 2.16e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMV---DESQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd12059      1 VWTAVFDYEASAEDELTLRRGDRVEVlskDSAVSGDEGWWTGKINDRVGIFPSNY 55

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 51.31 E-value: 2.20e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTK-KDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11820      5 ALYDFEAAEDNELTFKAGEIITVLDdSDPNWWKGSNHRGEGLFPANFV 52

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212836 [Multi-domain] Cd Length: 59 Bit Score: 51.60 E-value: 2.29e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNK--EDPDWWKGE-VNGQVGLFPSNYV 1167
Cdd:cd11903      6 LYPFSSVTEEELNFEKGETMEVIEKpeNDPEWWKCKnSRGQVGLVPKNYV 55

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 51.04 E-value: 2.42e-08

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKK-DGDWW------TGtvgdKAGVFPSNY 1012
Cdd:cd11845      2 YVALYDYEARTDDDLSFKKGDRLQILDDsDGDWWlarhlsTG----KEGYIPSNY 52

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 51.46 E-value: 2.53e-08

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                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11928      6 LYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCHGFLPASYIQC 54

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212789 [Multi-domain] Cd Length: 55 Bit Score: 51.27 E-value: 2.54e-08

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1120 GMYDYTAQNDD--ELAFNKGQIINVLNKEDpDWWKGEV-NGQVGLFPSNYVKL 1169
Cdd:cd11855      4 ALYPYDASPDDpnELSFEKGEILEVSDTSG-KWWQARKsNGETGICPSNYLQL 55

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 51.38 E-value: 2.64e-08

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                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd11949      4 ALFDFDPQEDGELGFRRGDFIeVMDNSDPNWWKGACHGQTGMFPRNYVT 52

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 51.20 E-value: 2.72e-08

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQARgkkrqIGWFPANYVKL 1093
Cdd:cd11875      2 ARVLFDYEAENEDELTLREGDIVTILSKDCEdkGWWKGELNGK-----RGVFPDNFVEP 55

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 51.56 E-value: 2.79e-08

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPD-----WWKG--EVNGQVGLFPSNYVK 1168
Cdd:cd11790      9 HDYTAEDTDELTFEKGDVILVIPFDDPEeqdegWLMGvkESTGCRGVFPENFTE 62

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 51.05 E-value: 2.85e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM---WWFGEVQGQKGWFPKSYVKLI 927
Cdd:cd12057      1 YCKVLFPYEAQNEDELTIKEGDIVTLISKDCIdagWWEGELNGRRGVFPDNFVKLL 56

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 51.20 E-value: 3.00e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11782      6 YNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQ 52

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 51.08 E-value: 3.17e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNK--EDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11952      3 VYALWDYSAEFPDELSFKEGDMVTVLRKdgEGTDWWWASLCGREGYVPRNYFGL 56

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 51.10 E-value: 3.47e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11927      5 ALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVNGIHGFFPTNFVQI 54

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 58.23 E-value: 3.48e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  299 EDEQQQLEKKLPVTFEDKKRENFErgnlELEKRRQALLEQQRKEQErlaQLERAEQERKERERQEQERKRQLELEKQLEK 378
Cdd:PTZ00121  1078 DFDFDAKEDNRADEATEEAFGKAE----EAKKTETGKAEEARKAEE---AKKKAEDARKAEEARKAEDARKAEEARKAED 1150

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  379 qrelerqreeERRKEIERREAAKRELERQRQLE----WERNRRQELLNQRN--KEQEDIVVLKAKKKTlEFELEALNDKK 452
Cdd:PTZ00121  1151 ----------AKRVEIARKAEDARKAEEARKAEdakkAEAARKAEEVRKAEelRKAEDARKAEAARKA-EEERKAEEARK 1219

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  453 HQLEGKLQDIRcRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIP--EKQILNDQLKQVQQNSLHRDSLVT 530
Cdd:PTZ00121  1220 AEDAKKAEAVK-KAEEAKKDAEEAKKAEEERNNEEIRKFEEARMAHFARRQAAIkaEEARKADELKKAEEKKKADEAKKA 1298

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  531 --LKRALEAKELARQHLR-DQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEK 607
Cdd:PTZ00121  1299 eeKKKADEAKKKAEEAKKaDEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEAKK 1378

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772  608 QKEEAQRRAQERDKQwlEHVQQEDEHQRPR----KLHEEEKLKREE 649
Cdd:PTZ00121  1379 KADAAKKKAEEKKKA--DEAKKKAEEDKKKadelKKAAAAKKKADE 1422

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212977 Cd Length: 53 Bit Score: 51.01 E-value: 3.60e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKEDP--DWWKGEVNGQVGLFPSNYV 1167
Cdd:cd12044      4 GLWDCFGDNPDELSFQRGDLIYILSKEYNmyGWWVGELNGIVGIVPKDYL 53

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 57.08 E-value: 3.62e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  399 AAKRELER-QRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIestn 477
Cdd:COG4942     31 QLQQEIAElEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAELAELEKEIAELRAELEAQKEEL---- 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  478 kSRELRIAEITHLQQQLQESQQMLG------RLIPEKQILNDQLKQVQQNSLHRDSLVTLKRALEAKelaRQHLRDQLDE 551
Cdd:COG4942    107 -AELLRALYRLGRQPPLALLLSPEDfldavrRLQYLKYLAPARREQAEELRADLAELAALRAELEAE---RAELEALLAE 182

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  552 VEKETRSKLQEIDIFNNQLKELreihNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRA 616
Cdd:COG4942    183 LEEERAALEALKAERQKLLARL----EKELAELAAELAELQQEAEELEALIARLEAEAAAAAERT 243

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212942 [Multi-domain] Cd Length: 54 Bit Score: 50.97 E-value: 3.81e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTGT--VGDKAGVFPSNYV 1013
Cdd:cd12009      3 IAQYDFVPSNERDLQLKKGEKLQVLKSDGEWWLAKslTTGKEGYIPSNYV 52

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 50.72 E-value: 3.81e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVdESQTGEpGWLGGELKGKTGWFPANYAE 760
Cdd:cd11803      3 CRALYDFEPENEGELGFKEGDIITL-TNQIDE-NWYEGMVNGQSGFFPVNYVE 53

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 50.72 E-value: 3.87e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEV-NGQVGLFPSNYVK 1168
Cdd:cd11998      2 RVRALYDYDGQEQDELSFKAGDELTKLEDEDEQgWCKGRLdSGQVGLYPANYVE 55

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 50.86 E-value: 3.91e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYVKL 1169
Cdd:cd11783      2 YVALYPYKPQKPDELELRKGEMYTVTEKCQDGWFKGTslRTGQSGVFPGNYVQP 55

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 50.59 E-value: 3.94e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGD-KAGVFPSNYV 1013
Cdd:cd11812      3 VALYDYTANRSDELTIHRGDIIRVLYKDNDnWWFGSLVNgQQGYFPANYV 52

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function unknown];

Pssm-ID: 443091 [Multi-domain] Cd Length: 379 Bit Score: 56.76 E-value: 4.03e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  423 QRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLqqqlqesqqmlg 502
Cdd:COG3883     17 QIQAKQKELSELQAELEAAQAELDALQAELEELNEEYNELQAELEALQAEIDKLQAEIAEAEAEIEER------------ 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  503 rlipeKQILNDQLKQVQQNSLHRDSLVTLkraLEAKELARqhLRDQLDEVEKETRSKLQEIDifnnQLKELREIHNKQQL 582
Cdd:COG3883     85 -----REELGERARALYRSGGSVSYLDVL---LGSESFSD--FLDRLSALSKIADADADLLE----ELKADKAELEAKKA 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  583 QKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQ 662
Cdd:COG3883    151 ELEAKLAELEALKAELEAAKAELEAQQAEQEALLAQLSAEEAAAEAQLAELEAELAAAEAAAAAAAAAAAAAAAAAAAAA 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  663 EAQDKLGRLFHQHQEPAKPAVQAPWSTAEKGPLTISAQENVKVVYYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGW 742
Cdd:COG3883    231 AAAAAAAAAAAAAASAAGAGAAGAAGAAAGSAGAAGAAAGAAGAGAAAASAAGGGAGGAGGGGGGGGAASGGSGGGSGGA 310

                          330
                   ....*....|....
gi 1061899772  743 LGGELKGKTGWFPA 756
Cdd:COG3883    311 GGVGSGGGAGAVVG 324

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 50.81 E-value: 4.10e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11844      5 LYDNVAESPDELAFRRGDILTVLEQNTAGlegWWLCSLRGRQGIAPGNRLKL 56

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 50.40 E-value: 4.16e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVL-EQQDMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11826      4 ALYDYTADKDDELSFQEGDIIYVTkKNDDGWYEGVLNGVTGLFPGNYV 51

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 50.77 E-value: 4.19e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE-VNGQVGLFPSNYVKL 1169
Cdd:cd11770      2 YEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAEnSKGNRGLVPKTYLKV 54

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 50.83 E-value: 4.38e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11974      6 LWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNEDREAWFPASFVRL 54

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 50.79 E-value: 4.56e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVdESQTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11978      5 ARYDFCARDMRELSLLKGDVVKI-YTKMSTNGWWRGEVNGRVGWFPSTYVEE 55

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 50.66 E-value: 4.67e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd12052      1 EAIVEFDYKAQHEDELTITVGDIITkIKKDDGGWWEGEIKGRRGLFPDNFVR 52

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 50.49 E-value: 4.98e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDEsQTGEpgWLGGELKGKTGWFPANYAEK 761
Cdd:cd11838      1 EYIALYPYESNEPGDLTFNAGDVILVTK-KDGE--WWTGTIGDRTGIFPSNYVRP 52

Second or C-terminal Src homology 3 domain of NADPH oxidase (Nox) Organizing protein 1; Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1 is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. NoxO1 contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of NoxO1. The tandem SH3 domains of NoxO1 interact with the PRR of p22phox, which also complexes with Nox1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212957 Cd Length: 53 Bit Score: 50.41 E-value: 4.98e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772 1124 YTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd12024      8 YEAQKEDELSVPAGVVVEVLQKSDNGWWLIRYNGRAGYVPSMYLQP 53

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 50.33 E-value: 5.17e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYV 924
Cdd:cd11964      2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDpNWWKGETPQGTGLFPSNFV 52

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 50.39 E-value: 5.51e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  963 EEFIAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11972      3 EKVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDgWYEGVMNGVTGLFPGNYV 54

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212692 [Multi-domain] Cd Length: 55 Bit Score: 50.44 E-value: 5.80e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE-VNGQVGLFPSNYV 1167
Cdd:cd11758      3 VRALFDFPGNDDEDLPFKKGEILTVIRKPEEQWWNARnSEGKTGMIPVPYV 53

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 50.36 E-value: 5.84e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILV-TKKDGDWWTGTVGD-----KAGVFPSNY 1012
Cdd:cd11883      3 VALYDFTPKSKNQLSFKAGDIIYVlNKDPSGWWDGVIISssgkvKRGWFPSNY 55

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 50.11 E-value: 6.13e-08

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11842      1 KAVALYDFAGEQPGDLAFQKGDIITILKKsdsQNDWWTGRIGGREGIFPANYVEL 55

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 50.20 E-value: 6.15e-08

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD--MWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11948      1 EAVALYSFQATESDELPFQKGDILKILNMEDdqNWYKAELQGREGYIPKNYIKV 54

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 50.11 E-value: 6.15e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVL-EQQDMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11827      1 QCKALYAYDAQDTDELSFNEGDIIEILkEDPSGWWTGRLRGKEGLFPGNYV 51

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 50.21 E-value: 6.68e-08

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLnKEDPDWWKGE--VNGQVGLFPSNYV 1167
Cdd:cd12005      1 LVVALYSYEPSHDGDLGFEKGEKLRIL-EQSGEWWKAQslTTGQEGFIPFNFV 52

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 50.26 E-value: 7.33e-08

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd11988      5 RALYPFEARNHDEMSFNAGDIIQVDEKtvgEPGWLYGSFQGNFGWFPCNYVE 56

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212932 [Multi-domain] Cd Length: 56 Bit Score: 49.94 E-value: 7.37e-08

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGEVN-GQVGLFPSNYV 1167
Cdd:cd11999      3 RVRAVYDYTGQEPDELSFKAGEELLKVEDEDEQgWCKGVTDgGAVGLYPANYV 55

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 49.96 E-value: 7.42e-08

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gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11919      7 FDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYIEL 54

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 49.80 E-value: 7.59e-08

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                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYV 924
Cdd:cd11951      2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDpNWWRGRISGRVGFFPRNYV 51

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 50.03 E-value: 8.00e-08

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGE--LKGKTGWFPANYAE 760
Cdd:cd11793      4 CVHAYTAQQPDELTLEEGDVVNV--LRKMPDGWYEGErlRDGERGWFPSSYTE 54

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 50.01 E-value: 8.02e-08

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                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVM----VDEsqtgepGWLGGELK--GKTGWFPANYAEK 761
Cdd:cd11789      2 YRAMYDYAAADDDEVSFQEGDVIInveiIDD------GWMEGTVQrtGQSGMLPANYVEL 55

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 50.00 E-value: 8.12e-08

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                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVmVDESQTGEpGWLGG--ELKGKTGWFPANYAEKI 762
Cdd:cd11934      5 YRAVYDYNAADEDEVSFQDGDTI-VNVQQIDD-GWMYGtvERTGDTGMLPANYVEAI 59

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 49.94 E-value: 8.14e-08

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDEsqTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11856      2 YVAIADYEAQGDDEISLQEGEVVEVLE--KNDSGWWYVRKGDKEGWVPASYLEP 53

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 50.00 E-value: 8.35e-08

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gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYVKL 1169
Cdd:cd11935      6 MYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGTVqrTGRTGMLPANYIEF 56

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 49.77 E-value: 8.58e-08

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 925
Cdd:cd11820      2 KVRALYDFEAAEDNELTFKAGEIITVLDDSDPnWWKGSNHRGEGLFPANFVT 53

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 49.82 E-value: 8.73e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILV-TKKDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd11950      4 ALYDFEALEDDELGFNSGDVIEVlDSSNPSWWKGRLHGKLGLFPANYVA 52

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 49.78 E-value: 8.78e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYV 1167
Cdd:cd11784      3 VALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLslVTGRVGIFPSNYV 53

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 49.83 E-value: 9.33e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd12073      3 AVALYDYQGEGDDEISFDPQETITDIEMVDEgWWKGTCHGHRGLFPANYVEL 54

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 49.72 E-value: 9.84e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1038 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYVKL 1093
Cdd:cd11840      1 QVIAlfPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNG-----QTGLFPSNYVEP 53

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 49.82 E-value: 1.02e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMV---DESQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd11876      4 ALFDYDARGEDELTLRRGQPVEVlskDAAVSGDEGWWTGKIGDKVGIFPSNY 55

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 49.63 E-value: 1.17e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNK--EDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11977      4 VARYNFAARDMRELSLREGDVVRIYSRigGDQGWWKGETNGRIGWFPSTYVE 55

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 49.63 E-value: 1.19e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKED---PDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11954      3 VYALWDYEAQNADELSFQEGDAITILRRKDdseTEWWWARLNDKEGYVPKNLLGL 57

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 49.25 E-value: 1.20e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1042 SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELqarGKKRQiGWFPANYVK 1092
Cdd:cd11825      7 DYRAQRPDELSFCKHAIITNVEKEDGGWWRGDY---GGKKQ-KWFPANYVE 53

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 49.44 E-value: 1.22e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  710 ALYPFESRSHDEITIQPGDIV----MVDEsqtgepGWLGGELKGKTGWFPANYAE 760
Cdd:cd12073      5 ALYDYQGEGDDEISFDPQETItdieMVDE------GWWKGTCHGHRGLFPANYVE 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 49.57 E-value: 1.22e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQV---GLFPSNYV 1167
Cdd:cd11966      1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPtrrGAFPVSFV 54

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212769 [Multi-domain] Cd Length: 54 Bit Score: 49.37 E-value: 1.28e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1124 YTAQNDDELAFNKGQIINVLN---KEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11835      8 YTAQAPDELSLEVGDIVSVIDmppPEESTWWRGKKGFQVGFFPSECV 54

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 49.19 E-value: 1.33e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11766      2 AVVKFNYEAQREDELSLRKGDRVLVLEKSSD--GWWRGECNGQVGWFPSNYVTE 53

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 49.18 E-value: 1.35e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11985      3 VALYKFLPQENNDLPLQPGDRVMVVDDSNEDWWKGKSGDRVGFFPANFVQ 52

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 49.63 E-value: 1.39e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMV---DESQTGEPGWLGG--ELKGKTGWFPANYAEKI 762
Cdd:cd11790      6 RATHDYTAEDTDELTFEKGDVILVipfDDPEEQDEGWLMGvkESTGCRGVFPENFTERI 64

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 49.03 E-value: 1.44e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQDM--WWFGEVQGQKGWFPKSY 923
Cdd:cd11778      3 EALYDYEAQGDDEISIRVGDRIAVIRGDDGsgWTYGEINGVKGLFPTSY 51

Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full length form of the previously-identified tumor supressor, p53-binding protein 2 (p53BP2). ASPP2 activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). It plays a central role in regulating apoptosis and cell growth; ASPP2-deficient mice show postnatal death. Downregulated expression of ASPP2 is frequently found in breast tumors, lung cancer, and diffuse large B-cell lymphoma where it is correlated with a poor clinical outcome. ASPP2 contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP2 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212886 [Multi-domain] Cd Length: 57 Bit Score: 49.18 E-value: 1.45e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11953      3 VYALWDYEGESDDELSFKEGDCMTILRREDEDeteWWWARLNDKEGYVPRNLLGL 57

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 49.10 E-value: 1.54e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11988      7 LYPFEARNHDEMSFNAGDIIQVDEKTvgEPGWLYGSFQGNFGWFPCNYVE 56

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 48.87 E-value: 1.56e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11874      4 VLFSYTPQNEDELELKVGDTIEVLGEVEEgWWEGKLNGKVGVFPSNFVKE 53

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 48.78 E-value: 1.58e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTgePGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11805      3 QALYDFNPQEPGELEFRRGDIITVLDSSD--PDWWKGELRGRVGIFPANYVQP 53

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 49.24 E-value: 1.59e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11977      5 ARYNFAARDMRELSLREGDVVRIYSRIGGDQGWWKGETNGRIGWFPSTYVEE 56

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 49.05 E-value: 1.59e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYVK 925
Cdd:cd11950      1 QVRALYDFEALEDDELGFNSGDVIEVLDSSNpSWWKGRLHGKLGLFPANYVA 52

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 49.00 E-value: 1.60e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQ---DMWWFGEVQGQKGWFPKSYV 924
Cdd:cd12142      3 RVLFDYNPVAPDELALKKGDVIEVISKEtedEGWWEGELNGRRGFFPDNFV 53

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 49.03 E-value: 1.65e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-----WWFGEVQGQKGWFPKSYVK 925
Cdd:cd12141      4 AVYTFKARSPNELSVSANQRVRILEFSDLtgnkeWWLAEANGQKGYVPSNYIR 56

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212978 Cd Length: 53 Bit Score: 48.74 E-value: 1.74e-07

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                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKEDP--DWWKGEVNGQVGLFPSNYV 1167
Cdd:cd12045      4 GLWDCTGDQPDELSFKRGDTIYILSKEYNrfGWWVGEMKGTIGLVPKAYI 53

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 48.92 E-value: 1.81e-07

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                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772  970 TYESSEqgdLTFQQGDVILVTK-KDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11828     10 TMDPEE---LGFKAGDVIEVLDmSDKDWWWGSIRDEEGWFPASFVRL 53

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212781 [Multi-domain] Cd Length: 58 Bit Score: 49.09 E-value: 1.90e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTGTVGDKA------GVFPSNYV 1013
Cdd:cd11847      2 YKALWDFKARGDEELSFQAGDQFRIAERSGDWWTALKLDRAggvvaqGFVPNNYL 56

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 48.35 E-value: 2.05e-07

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                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELqargKKRQIGWFPA 1088
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRN----KGGKEGLIPS 47

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 48.53 E-value: 2.16e-07

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                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 925
Cdd:cd12061      3 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGgWWEGTHNGRTGWFPSNYVR 52

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 48.48 E-value: 2.21e-07

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                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGDKA-GVFPSNYV 1013
Cdd:cd11825      4 ALYDYRAQRPDELSFCKHAIITnVEKEDGGWWRGDYGGKKqKWFPANYV 52

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 48.50 E-value: 2.26e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVL--EQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11875      1 KARVLFDYEAENEDELTLREGDIVTILskDCEDKgWWKGELNGKRGVFPDNFVEP 55

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 48.65 E-value: 2.28e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANYAEK 761
Cdd:cd11833      1 TYVALYKFKPQENEDLEMRPGDKITLLDDSNED--WWKGKIEDRVGFFPANFVQR 53

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 48.67 E-value: 2.37e-07

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                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd12073      4 VALYDYQGEGDDEISFDPQETITdIEMVDEGWWKGTCHGHRGLFPANYVEL 54

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 48.55 E-value: 2.42e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGD-KAGVFPSNYVRL 1015
Cdd:cd11960      4 ALYDYQAADDTEISFDPGDIITdIEQIDEGWWRGTGPDgTYGLFPANYVEL 54

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 48.25 E-value: 2.44e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSY 923
Cdd:cd11818      1 KARALYDFTGENEDELSFKAGDIITELESIDEEWMsGELRGKSGIFPKNF 50

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 48.46 E-value: 2.46e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1042 SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYVK 1092
Cdd:cd12060      9 NFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKT-----GWFPSNYVR 54

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 48.38 E-value: 2.48e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11928      4 KALYSYEGKEPGDLKFNKGDIIILRRKVDeNWYHGELNGCHGFLPASYIQC 54

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 48.28 E-value: 2.53e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1061899772 1049 EQLTLAPGQLILIRKKNPGGWWEGElqargKKRQIGWFPANYV 1091
Cdd:cd11829     15 QGLSFEAGELIRVLQAPDGGWWEGE-----KDGLRGWFPASYV 52

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 48.48 E-value: 2.58e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIV-MVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11884      1 YVVAVRAYITRDQTLLSFHKGDVIkLLPKEGPLDPGWLFGTLDGRSGAFPKEYVQ 55

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 54.57 E-value: 2.60e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  550 DEVEKETRSKLQEIDIFNNQLKELR----EIHNKQQLQKQKSMEAERLKQKEQERKIIEL--EKQKEEAQRRAQERDKQW 623
Cdd:pfam15709  376 EELELEQQRRFEEIRLRKQRLEEERqrqeEEERKQRLQLQAAQERARQQQEEFRRKLQELqrKKQQEEAERAEAEKQRQK 455

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1061899772  624 LEHVQQEDEHQRPRKLHEEEKLkrEESVKKKDGEEKGKQEAQDK 667
Cdd:pfam15709  456 ELEMQLAEEQKRLMEMAEEERL--EYQRQKQEAEEKARLEAEER 497

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 51.19 E-value: 2.70e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  329 EKRRQALLEQQRKEQERLAQLERAEQERKE-RERQEQERKRQLELEKQLEKQRELERQREEERrkeierreaAKRELERQ 407
Cdd:pfam05672   18 EKRRQAREQREREEQERLEKEEEERLRKEElRRRAEEERARREEEARRLEEERRREEEERQRK---------AEEEAEER 88

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  408 RQLEWERNRRQEllnQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGK 458
Cdd:pfam05672   89 EQREQEEQERLQ---KQKEEAEAKAREEAERQRQEREKIMQQEEQERLERK 136

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 48.28 E-value: 2.74e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  709 RALYPFESRSHDE-ITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd11829      3 RTLYAFTGEQHQQgLSFEAGELIRV--LQAPDGGWWEGEKDGLRGWFPASY 51

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212839 [Multi-domain] Cd Length: 55 Bit Score: 48.28 E-value: 2.78e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKG-EVNGQVGLFPSNYV 1167
Cdd:cd11906      3 VVALYDYTPMNAQDLQLRKGEEYVILEESNLPWWRArDKNGREGYIPSNYV 53

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 48.52 E-value: 2.79e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11974      3 AEALWDHVTMDDQELAFKAGDVIRVLEASNKdWWWGRNEDREAWFPASFVRL 54

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 48.16 E-value: 2.89e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQ-GQKGWFPKSYVKL 926
Cdd:cd11960      2 ARALYDYQAADDTEISFDPGDIITDIEQIDEgWWRGTGPdGTYGLFPANYVEL 54

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 48.08 E-value: 2.92e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIV----MVDEsqtgepGWLGGEL-KGKTGWFPANYAE 760
Cdd:cd11819      3 KALYDYQAAEDNEISFVEGDIItqieQIDE------GWWLGVNaKGQKGLFPANYVE 53

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 48.73 E-value: 2.92e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd12003      6 LYDNAAESPEELSFRRGDVLMVLKREHGSlpgWWLCSLHGQQGIAPANRLRL 57

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 48.10 E-value: 3.27e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGK-----TGWFPANYAEK 761
Cdd:cd11839      3 QVIAPFTATAENQLSLAVGQLVLVRKKSPS--GWWEGELQARgkkrqIGWFPANYVKL 58

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 48.14 E-value: 3.29e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1042 SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVK 1092
Cdd:cd12061      7 NFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGR-----TGWFPSNYVR 52

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 48.14 E-value: 3.30e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQ--TGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11800      1 YYYALYTFEARSPGELSVTEGQVVTVLEKHdlKGNPEWWLVEDRGKQGYVPSNYLAK 57

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212721 [Multi-domain] Cd Length: 53 Bit Score: 48.10 E-value: 3.31e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  966 IAMYTYESS---EQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNY 1012
Cdd:cd11787      3 KALYDFEMKdedEKDCLTFKKGDVITVIRRvDENWAEGRLGDKIGIFPISF 53

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 48.14 E-value: 3.32e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11824      2 YSVLYDYTAQEDDELSISKGDVVAVIEKgEDGWWTVERNGQKGLVPGTYLEK 53

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 48.01 E-value: 3.33e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11929      2 RAKALCNYRGHNPGDLKFNKGDVILLRRQLDEnWYLGEINGVSGIFPASSVEV 54

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212941 [Multi-domain] Cd Length: 56 Bit Score: 48.18 E-value: 3.43e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGE--VNGQVGLFPSNYV 1167
Cdd:cd12008      3 VALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHslTTGQTGYIPSNYV 53

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212998 [Multi-domain] Cd Length: 54 Bit Score: 48.06 E-value: 3.55e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIvMVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd12065      3 KAVYPCEAEHSSELSFEVGAI-FEDVTLSREPGWLEGTLNGKRGLIPENYVE 53

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212940 [Multi-domain] Cd Length: 58 Bit Score: 48.11 E-value: 3.63e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTG--TVGDKAGVFPSNYVRLKD 1017
Cdd:cd12007      3 FVALYDYEARTTEDLSFKKGERFqIINNTEGDWWEArsIATGKNGYIPSNYVAPAD 58

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 48.04 E-value: 3.71e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  709 RALYPFESRSHD-EITIQPGDIVMVDE--SQTGEP-GWLGGELK-GKTGWFPANYAE 760
Cdd:cd11771      3 RALYDFTPENPEmELSLKKGDIVAVLSktDPLGRDsEWWKGRTRdGRIGWFPSNYVE 59

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 47.85 E-value: 3.96e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMV-DESqtgEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11820      4 RALYDFEAAEDNELTFKAGEIITVlDDS---DPNWWKGSNHRGEGLFPANFVTA 54

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 54.59 E-value: 4.14e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  305 LEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQ-----ERLAQLERAEQERkeRERQEQERKRQLELEKQLEKQ 379
Cdd:TIGR00618  175 LDQYTQLALMEFAKKKSLHGKAELLTLRSQLLTLCTPCMpdtyhERKQVLEKELKHL--REALQQTQQSHAYLTQKREAQ 252

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  380 relerqreeerrkeierreaaKRELERQRQLEWERNRRQELLNQ--RNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEG 457
Cdd:TIGR00618  253 ---------------------EEQLKKQQLLKQLRARIEELRAQeaVLEETQERINRARKAAPLAAHIKAVTQIEQQAQR 311

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  458 KLQDIRCRLTT-----------QRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQI-LNDQLKQVQQNSLHR 525
Cdd:TIGR00618  312 IHTELQSKMRSrakllmkraahVKQQSSIEEQRRLLQTLHSQEIHIRDAHEVATSIREISCQQHtLTQHIHTLQQQKTTL 391

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  526 DSLVTLKRALEAKELARQHLRDQLDEVEKETRSKL------QEIDIFNNQLKELrEIHNKQQLQKQKSMEAERLKQKEQE 599
Cdd:TIGR00618  392 TQKLQSLCKELDILQREQATIDTRTSAFRDLQGQLahakkqQELQQRYAELCAA-AITCTAQCEKLEKIHLQESAQSLKE 470

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  600 RKiiELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRP---RKLHEEEKL 645
Cdd:TIGR00618  471 RE--QQLQTKEQIHLQETRKKAVVLARLLELQEEPCPlcgSCIHPNPAR 517

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 48.07 E-value: 4.17e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYVK 1168
Cdd:cd11934      7 AVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYGTVerTGDTGMLPANYVE 57

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 48.08 E-value: 4.37e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMvdESQTGEPGWLGGELK--GKTGWFPANYAEKI 762
Cdd:cd11933      4 FRAMYDYRAADDDEVSFKDGDTIV--NVQTIDEGWMYGTVQrtGKTGMLPANYVEAI 58

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 47.96 E-value: 4.38e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQ---GQKGWFPKSYVKL 926
Cdd:cd11872      4 AIYNFQGDGEHQLSLQVGDTVQILEECEGWYRGFSLrnkSLKGIFPKSYVHI 55

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 47.91 E-value: 4.41e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILV-TKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11956      3 EAVACFDYTGRTAQELSFKRGDVLLLhSKASSDWWRGEHNGMRGLIPHKYISV 55

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 47.67 E-value: 4.43e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1038 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYVKL 1093
Cdd:cd11996      2 QVIAmyDYTANNEDELSFSKGQLINVLNKDDPDWWQGEING-----VTGLFPSNYVKM 54

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212874 Cd Length: 57 Bit Score: 47.98 E-value: 4.59e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKED----PDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11941      1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDkkgsPEWSLVEVNGQRGYVPSSYL 55

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 47.69 E-value: 4.73e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMvdESQTGEPGWLGGELK--GKTGWFPANYAEKI 762
Cdd:cd11935      3 YRAMYDYSAQDEDEVSFRDGDYIV--NVQPIDEGWMYGTVQrtGRTGMLPANYIEFV 57

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 48.06 E-value: 4.85e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKG-WFPKSYVKLIS 928
Cdd:cd11970      7 KALFDYKAQREDELTFTKNAIIQNVEKQEgGWWRGDYGGKKQlWFPSNYVEEIS 60

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 47.69 E-value: 4.95e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGElqarGKKRQIGWFPANYVKL 1093
Cdd:cd11819      2 AKALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGV----NAKGQKGLFPANYVEL 54

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 47.69 E-value: 5.06e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQ---KGWFPKSY 923
Cdd:cd11821      2 VRALYDCQADNDDELTFSEGEIIVVTGEEDdEWWEGHIEGDpsrRGVFPVSF 53

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 47.64 E-value: 5.07e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMV-DESqtgEPGWLGGELKGKTGWFPANY 758
Cdd:cd11964      4 RAIYDFEAAEDNELTFKAGDIITIlDDS---DPNWWKGETPQGTGLFPSNF 51

Src homology 3 domain of Slit-Robo GTPase Activating Proteins 1, 2, and 3; srGAP1, also called Rho GTPase-Activating Protein 13 (ARHGAP13), is a Cdc42- and RhoA-specific GAP and is expressed later in the development of central nervous system tissues. srGAP2 is expressed in zones of neuronal differentiation. It plays a role in the regeneration of neurons and axons. srGAP3, also called MEGAP (MEntal disorder associated GTPase-Activating Protein), is a Rho GAP with activity towards Rac1 and Cdc42. It impacts cell migration by regulating actin and microtubule cytoskeletal dynamics. The association between srGAP3 haploinsufficiency and mental retardation is under debate. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212888 [Multi-domain] Cd Length: 53 Bit Score: 47.63 E-value: 5.08e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11955      1 EAIAKFDYVGRSARELSFKKGASLLLYHRASDDWWEGRHNGIDGLVPHQYI 51

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 47.34 E-value: 5.19e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVK 925
Cdd:cd11782      1 EARAKYNFNADTGVELSFRKGDVITLTRRVDENWYeGRIGGRQGIFPVSYVQ 52

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 47.32 E-value: 5.37e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYV 1091
Cdd:cd11826      4 ALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGV-----TGLFPGNYV 51

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 47.60 E-value: 5.46e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11986      3 VALYRFKALEKDDLDFHPGERITVIDDSNEEWWRGKIGEKTGYFPMNFI 51

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 47.31 E-value: 5.48e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd11992      4 ALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVR 51

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 47.26 E-value: 5.67e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDgWWRGECNGQVGWFPSNYV 51

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 47.37 E-value: 5.89e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-----WWFGEVQGQKGWFPKSY 923
Cdd:cd11800      4 ALYTFEARSPGELSVTEGQVVTVLEKHDLkgnpeWWLVEDRGKQGYVPSNY 54

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 53.00 E-value: 6.22e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  294 EEPVLEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQALLEQ-QRKEQERLAQLERAEQERKEReRQEQERKRQLEL 372
Cdd:pfam13868   37 EEKEEERRLDEMMEEERERALEEEEEKEEERKEERKRYRQELEEQiEEREQKRQEEYEEKLQEREQM-DEIVERIQEEDQ 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  373 EKQLEKQrelerqreeerrkeiERREAAKRELERQRQlewERNRRQELLNQRNKEQEDIVVLKAKKKTLEFelEALNDKK 452
Cdd:pfam13868  116 AEAEEKL---------------EKQRQLREEIDEFNE---EQAEWKELEKEEEREEDERILEYLKEKAERE--EEREAER 175

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  453 HQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEithlqqqlqesqqmlgRLIPEKQILNDQLKQVQQnslhrdslvtLK 532
Cdd:pfam13868  176 EEIEEEKEREIARLRAQQEKAQDEKAERDELRAK----------------LYQEEQERKERQKEREEA----------EK 229

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  533 RALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKsmeaERLKQKEQERKIIELEKQKEEA 612
Cdd:pfam13868  230 KARQRQELQQAREEQIELKERRLAEEAEREEEEFERMLRKQAEDEEIEQEEAEK----RRMKRLEHRRELEKQIEEREEQ 305

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1061899772  613 QRRAQERDKQWLEHVQQEDEHQrpRKLHEEEKLK 646
Cdd:pfam13868  306 RAAEREEELEEGERLREEEAER--RERIEEERQK 337

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 47.34 E-value: 6.35e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYV 1091
Cdd:cd11901      4 AYVKFNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQ-----VGWFPSNYV 53

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 47.31 E-value: 6.53e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN--GQVGLFPSNYVK 1168
Cdd:cd11933      7 MYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGTVQrtGKTGMLPANYVE 56

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 47.33 E-value: 6.58e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd12076      3 YTVIYPYTARDQDEINLEKGAVVEV--IQKNLEGWWKIRYQGKEGWAPASYLKK 54

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 47.25 E-value: 6.85e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQ--QDMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd11976      2 AKARYDFCARDRSELSLKEGDIIKILNKkgQQGWWRGEIYGRVGWFPANYVE 53

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 47.12 E-value: 6.93e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVT--KKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11948      1 EAVALYSFQATESDELPFQKGDILKILnmEDDQNWYKAELQGREGYIPKNYIKV 54

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 47.29 E-value: 7.35e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11991      4 AMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTVGDKTGVFPSNYVRP 52

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212939 [Multi-domain] Cd Length: 56 Bit Score: 47.35 E-value: 7.69e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTG---TVGDkAGVFPSNYV 1013
Cdd:cd12006      3 FVALYDYEARTEDDLSFHKGEKFqILNSSEGDWWEArslTTGE-TGYIPSNYV 54

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 47.24 E-value: 7.89e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11929      5 ALCNYRGHNPGDLKFNKGDVILLRRQlDENWYLGEINGVSGIFPASSVEV 54

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins in this family are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.

Pssm-ID: 464768 [Multi-domain] Cd Length: 374 Bit Score: 52.73 E-value: 8.19e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  337 EQQRKEQERLAQLERAEQERKERERQEQ-ERKRQLELEKQLE------KQRELERQREEERRKEIERREAAKRELERQRQ 409
Cdd:pfam15558   20 EQRMRELQQQAALAWEELRRRDQKRQETlERERRLLLQQSQEqwqaekEQRKARLGREERRRADRREKQVIEKESRWREQ 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  410 LEWERNRRQELLNQRNKEQEdivvlkAKKKTLEFEL----EALNDKKHQLEGKLQDI--RCRLTTQRQEIESTNKSRELR 483
Cdd:pfam15558  100 AEDQENQRQEKLERARQEAE------QRKQCQEQRLkekeEELQALREQNSLQLQERleEACHKRQLKEREEQKKVQENN 173

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  484 IAEithlqqqlqesqqmlgrlipekqILNDQLKQVQQNSLHRDSLVTLKRALEAKelarqHLRDQldevekETRSKLQEI 563
Cdd:pfam15558  174 LSE-----------------------LLNHQARKVLVDCQAKAEELLRRLSLEQS-----LQRSQ------ENYEQLVEE 219

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  564 difnnQLKELREIHNKQQLQKQKSME-AERLKQKEQERK--IIELEKQK-EEAQRRAQERDKQWLEHVQQ-----EDEHQ 634
Cdd:pfam15558  220 -----RHRELREKAQKEEEQFQRAKWrAEEKEEERQEHKeaLAELADRKiQQARQVAHKTVQDKAQRARElnlerEKNHH 294

                          330
                   ....*....|....*.
gi 1061899772  635 RPR-KLHEEEKLKREE 649
Cdd:pfam15558  295 ILKlKVEKEEKCHREG 310

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 46.86 E-value: 8.23e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd11856      1 SYVAIADYEAQGDDEISLQEGEVVEVLEKnDSGWWYVRKGDKEGWVPASYLE 52

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 47.30 E-value: 8.29e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  961 SGEEFIAMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTV---GDKaGVFPSNYV 1013
Cdd:cd11934      1 GGKRYRAVYDYNAADEDEVSFQDGDTIVnVQQIDDGWMYGTVertGDT-GMLPANYV 56

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 46.92 E-value: 8.33e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDV--ILVTKKDGdWWTG--TVGDKaGVFPSNYVRL 1015
Cdd:cd11770      1 LYEALSDFQAEQEGDLSFKKGEVlrIISKRADG-WWLAenSKGNR-GLVPKTYLKV 54

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212743 [Multi-domain] Cd Length: 53 Bit Score: 47.01 E-value: 8.42e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11809      1 EATAQFDYTGRSERELSFKKGDSLtLYRQVSDDWWRGQLNGQDGLVPHKYITL 53

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 46.94 E-value: 8.44e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGD----WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11884      3 VAVRAYITRDQTLLSFHKGDVIKLLPKEGPldpgWLFGTLDGRSGAFPKEYV 54

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 46.95 E-value: 8.45e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANYAE 760
Cdd:cd11781      3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKN--WYEGEHNGRVGIFPASYVE 52

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 47.11 E-value: 8.47e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKED----PDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12141      5 VYTFKARSPNELSVSANQRVRILEFSDltgnKEWWLAEANGQKGYVPSNYIR 56

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 46.97 E-value: 8.61e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKDG---DWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11836      4 ALYAFEARNPDEISFQPGDIIQVDESQVaepGWLAGELKGKTGWFPANYV 53

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 46.87 E-value: 9.05e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1038 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYVKL 1093
Cdd:cd11995      2 QVIGmyDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNG-----QVGLFPSNYVKL 54

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 53.52 E-value: 9.09e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  299 EDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQL--ERAEQERkERERQEQERKRQLELEKQL 376
Cdd:TIGR02168  723 ELSRQISALRKDLARLEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAeeELAEAEA-EIEELEAQIEQLKEELKAL 801

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  377 EKQrelerqreeerrkeierREAAKRELERQRQ-LEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNdkkHQL 455
Cdd:TIGR02168  802 REA-----------------LDELRAELTLLNEeAANLRERLESLERRIAATERRLEDLEEQIEELSEDIESLA---AEI 861

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  456 EgklqdircRLTTQRQEIEStnksrelriaEITHlqqqlqesqqmlgrlipekqILNDQLKQVQQNSLHRDSLVTLKRAL 535
Cdd:TIGR02168  862 E--------ELEELIEELES----------ELEA--------------------LLNERASLEEALALLRSELEELSEEL 903

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  536 EAKELARQHLRDQLDEV-EKETRSKLQEIDIfnnqlkELREIHNKQQLQKQKSMEAERLKQK---------EQERKIIEL 605
Cdd:TIGR02168  904 RELESKRSELRRELEELrEKLAQLELRLEGL------EVRIDNLQERLSEEYSLTLEEAEALenkieddeeEARRRLKRL 977


                   ....*.
gi 1061899772  606 EKQKEE 611
Cdd:TIGR02168  978 ENKIKE 983

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 46.94 E-value: 9.25e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYV 924
Cdd:cd11963      3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDAnWWKGENHRGVGLFPSNFV 53

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 46.74 E-value: 9.26e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVdESQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd11812      4 ALYDYTANRSDELTIHRGDIIRV-LYKDNDNWWFGSLVNGQQGYFPANY 51

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 46.72 E-value: 9.31e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTK-KDGDWWTGT-VGDKA-GVFPSNYV 1013
Cdd:cd11889      4 AVYSWAGETEGDLGFLEGDLIEVLSiGDGSWWSGKlRRNGAeGIFPSNFV 53

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 53.26 E-value: 9.48e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  329 EKRRQALLEQQRKEQERLAQlerAEQERKERERQEQerkrQLELEK-QLEKQRELERQREEERRKEIERREAAKRELER- 406
Cdd:pfam01576    4 EEEMQAKEEELQKVKERQQK---AESELKELEKKHQ----QLCEEKnALQEQLQAETELCAEAEEMRARLAARKQELEEi 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  407 ----QRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTT---QRQEIESTNKS 479
Cdd:pfam01576   77 lhelESRLEEEEERSQQLQNEKKKMQQHIQDLEEQLDEEEAARQKLQLEKVTTEAKIKKLEEDILLledQNSKLSKERKL 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  480 RELRIAEITHLQQQLQESQQMLGRLIPEKQI----LNDQLKQVQQNslhRDSLVTLKRALEAK--ELARQH--------- 544
Cdd:pfam01576  157 LEERISEFTSNLAEEEEKAKSLSKLKNKHEAmisdLEERLKKEEKG---RQELEKAKRKLEGEstDLQEQIaelqaqiae 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  545 LRDQLDEVEKETRSKLQEID----IFNNQLKELREIHNkQQLQKQKSMEAERL--KQKEQERKII--ELEKQKEEAQrra 616
Cdd:pfam01576  234 LRAQLAKKEEELQAALARLEeetaQKNNALKKIRELEA-QISELQEDLESERAarNKAEKQRRDLgeELEALKTELE--- 309

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1061899772  617 qerDKQWLEHVQQEDEHQRPRKLHEEEKLKREES 650
Cdd:pfam01576  310 ---DTLDTTAAQQELRSKREQEVTELKKALEEET 340

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 46.86 E-value: 1.00e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWegelQARGKKRQiGWFPANYVK 1092
Cdd:cd11856      4 AIADYEAQGDDEISLQEGEVVEVLEKNDSGWW----YVRKGDKE-GWVPASYLE 52

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 46.76 E-value: 1.04e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGDKAG-VFPSNYV 1013
Cdd:cd11969      4 ALYDYRAKRSDELSFCKGALIHnVSKETGGWWKGDYGGKVQhYFPSNYV 52

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 53.05 E-value: 1.04e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  333 QALLEQQRKEQERLAQLERAEQ------ERKERERQEQERKRQLELEKQLEKQ--RELERQREEERRKEIERREAAKREL 404
Cdd:TIGR00618  156 QFLKAKSKEKKELLMNLFPLDQytqlalMEFAKKKSLHGKAELLTLRSQLLTLctPCMPDTYHERKQVLEKELKHLREAL 235

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  405 ERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLE-----GKLQDIRCRLTTQRQEIESTNKS 479
Cdd:TIGR00618  236 QQTQQSHAYLTQKREAQEEQLKKQQLLKQLRARIEELRAQEAVLEETQERINrarkaAPLAAHIKAVTQIEQQAQRIHTE 315

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  480 RELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDSLVTLKRALEAKELARQHLR---DQLDEVEKET 556
Cdd:TIGR00618  316 LQSKMRSRAKLLMKRAAHVKQQSSIEEQRRLLQTLHSQEIHIRDAHEVATSIREISCQQHTLTQHIHtlqQQKTTLTQKL 395

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  557 RSKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQER---------KIIELEKQKEEAQRRAQERDKQWLEHV 627
Cdd:TIGR00618  396 QSLCKELDILQREQATIDTRTSAFRDLQGQLAHAKKQQELQQRYaelcaaaitCTAQCEKLEKIHLQESAQSLKEREQQL 475

                          330       340
                   ....*....|....*....|...
gi 1061899772  628 QQ-EDEHQRPRKLHEEEKLKREE 649
Cdd:TIGR00618  476 QTkEQIHLQETRKKAVVLARLLE 498

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 46.54 E-value: 1.06e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTV---GDKAGVFPSNY 1012
Cdd:cd11821      4 ALYDCQADNDDELTFSEGEIIVVTGEeDDEWWEGHIegdPSRRGVFPVSF 53

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 46.75 E-value: 1.07e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILV-TKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11870      3 VALHRYEAQGPEDLGFREGDTIDVlSEVNEAWLEGHSDGRVGIFPKCFV 51

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 46.84 E-value: 1.09e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11921      7 FDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGRVGIFPANYVEV 54

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 47.01 E-value: 1.11e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11975      9 AVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDDEEGWFPASFVRL 58

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 46.56 E-value: 1.12e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  709 RALYPFESRSHDEITIQPGDIV-MVDESqtgEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11874      3 KVLFSYTPQNEDELELKVGDTIeVLGEV---EEGWWEGKLNGKVGVFPSNFVK 52

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 46.48 E-value: 1.13e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11927      3 AKALYNYEGKEPGDLKFSKGDIIILRRQVDEnWYHGEVNGIHGFFPTNFVQI 54

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 46.56 E-value: 1.15e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGE--VQGQKGWFPKSYV 924
Cdd:cd11793      1 QVQCVHAYTAQQPDELTLEEGDVVNVLRKmPDGWYEGErlRDGERGWFPSSYT 53

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 46.64 E-value: 1.15e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYV 1091
Cdd:cd11827      2 CKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRL--RGKE---GLFPGNYV 51

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 46.36 E-value: 1.18e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11950      3 RALYDFEALEDDELGFNSGDVIEVLDSS--NPSWWKGRLHGKLGLFPANYVA 52

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212933 Cd Length: 57 Bit Score: 46.80 E-value: 1.19e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPD---WWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd12000      6 LYDNKADCSDELAFRRGDILTVLEQNVPGsegWWKCLLHGRQGLAPANRLQL 57

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 46.53 E-value: 1.23e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGG--ELKGKTGWFPANYAEK 761
Cdd:cd11780      2 YRALYSYTPQNEDELELREGDIVYV--MEKCDDGWFVGtsERTGLFGTFPGNYVAR 55

Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. Rlk is expressed in T-cells and mast cell lines, and is a key component of T-cell receptor (TCR) signaling. It is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212840 [Multi-domain] Cd Length: 55 Bit Score: 46.49 E-value: 1.25e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN-GQVGLFPSNYV 1167
Cdd:cd11907      2 QVKALYDFLPREPSNLALKRAEEYLILEQYDPHWWKARDRyGNEGLIPSNYV 53

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 46.07 E-value: 1.29e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYVK 1092
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGIN--TGRT---GLVPANYVE 49

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 46.48 E-value: 1.31e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKDGD--WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11976      4 ARYDFCARDRSELSLKEGDIIKILNKKGQqgWWRGEIYGRVGWFPANYV 52

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 46.47 E-value: 1.32e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQ--QDMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd11830      2 AKARYDFCARDMRELSLKEGDVVKIYNKkgQQGWWRGEINGRIGWFPSTYVE 53

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212941 [Multi-domain] Cd Length: 56 Bit Score: 46.64 E-value: 1.37e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTG---TVGdKAGVFPSNYV 1013
Cdd:cd12008      2 FVALYDYESRTETDLSFKKGERLqIVNNTEGDWWLAhslTTG-QTGYIPSNYV 53

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 46.33 E-value: 1.40e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11951      4 AQYDFSAEDPSQLSFRRGDIIEVLDCpDPNWWRGRISGRVGFFPRNYV 51

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 46.18 E-value: 1.50e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12076      6 IYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEGWAPASYLK 53

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212695 [Multi-domain] Cd Length: 57 Bit Score: 46.20 E-value: 1.50e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1116 CQVIgmYDYTAQNDDELAFNKGQIINVLNKEDPDWW-KG-EVNGQVGLFPSNYVKL 1169
Cdd:cd11761      4 CKVL--YSYEAQRPDELTITEGEELEVIEDGDGDGWvKArNKSGEVGYVPENYLQF 57

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 46.33 E-value: 1.54e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11947      1 EARGKFDFTASGEDELSFKKGDVLKILSSDDIWFKAELNGEEGYVPKNFV 50

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 46.30 E-value: 1.59e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12016      2 KYITTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGKEGWAPATYLK 53

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 46.19 E-value: 1.65e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11782      1 EARAKYNFNADTGVELSFRKGDVITLTRRvDENWYEGRIGGRQGIFPVSYV 51

Mitotic checkpoint protein; This family consists of several eukaryotic mitotic checkpoint (Mitotic arrest deficient or MAD) proteins. The mitotic spindle checkpoint monitors proper attachment of the bipolar spindle to the kinetochores of aligned sister chromatids and causes a cell cycle arrest in prometaphase when failures occur. Multiple components of the mitotic spindle checkpoint have been identified in yeast and higher eukaryotes. In S.cerevisiae, the existence of a Mad1-dependent complex containing Mad2, Mad3, Bub3 and Cdc20 has been demonstrated.

Pssm-ID: 461677 [Multi-domain] Cd Length: 660 Bit Score: 52.44 E-value: 1.75e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  301 EQQQLEKKLPVTFEDKKRENFE--RGNLELEKRRQALLEQQRKE-------QERLAQLERAEQERKERERQEQERKRQL- 370
Cdd:pfam05557    3 ELIESKARLSQLQNEKKQMELEhkRARIELEKKASALKRQLDREsdrnqelQKRIRLLEKREAEAEEALREQAELNRLKk 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  371 ----ELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQedivvlKAKKKTLEFELE 446
Cdd:pfam05557   83 kyleALNKKLNEKESQLADAREVISCLKNELSELRRQIQRAELELQSTNSELEELQERLDLL------KAKASEAEQLRQ 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  447 ALNDKKHQL---EGKLQDIRCRLTTQRQ--EIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQL----KQ 517
Cdd:pfam05557  157 NLEKQQSSLaeaEQRIKELEFEIQSQEQdsEIVKNSKSELARIPELEKELERLREHNKHLNENIENKLLLKEEVedlkRK 236

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  518 VQQNSLHRDSLVTLKRALEA--------KELARQH---------LRDQLDEVEKETRSKLQEIDIFNNQLKELReihnKQ 580
Cdd:pfam05557  237 LEREEKYREEAATLELEKEKleqelqswVKLAQDTglnlrspedLSRRIEQLQQREIVLKEENSSLTSSARQLE----KA 312

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  581 QLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRR----AQERD--KQWLE 625
Cdd:pfam05557  313 RRELEQELAQYLKKIEDLNKKLKRHKALVRRLQRRvlllTKERDgyRAILE 363

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 46.18 E-value: 1.79e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQD---MWW-FGEVQGQKGWFPKSYVKL 926
Cdd:cd11904      4 QALYPFSSSNDEELNFEKGEVMDVIEKPEndpEWWkCRKANGQVGLVPKNYVTV 57

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 46.18 E-value: 1.80e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQG-----QKGWFPKSYVKL 926
Cdd:cd11839      2 AQVIAPFTATAENQLSLAVGQLVLVRKKSPSgWWEGELQArgkkrQIGWFPANYVKL 58

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 45.87 E-value: 1.81e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11959      3 VALYDYQAADDDEISFDPDDIITnIEMIDEGWWRGVCRGKYGLFPANYVEL 53

First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The first SH3 domain of Nck proteins preferentially binds the PxxDY sequence, which is present in the CD3e cytoplasmic tail. This binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212699 [Multi-domain] Cd Length: 51 Bit Score: 45.87 E-value: 1.86e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPdWWKGE-VNGQVGLFPSNYV 1167
Cdd:cd11765      2 VVAKYDYTAQGDQELSIKKNEKLTLLDDSKH-WWKVQnSSNQTGYVPSNYV 51

Centrosomal protein of 63 kDa; CEP63 is a family of eukaryotic proteins involved in centriole activity.

Pssm-ID: 465338 [Multi-domain] Cd Length: 264 Bit Score: 50.59 E-value: 1.96e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  299 EDEQQQLEKKLPVTFEDKKREnFERGNLELEKR----------RQALLEQQRKEQERL-AQLERAEQERKE--RERQEQE 365
Cdd:pfam17045    5 EAELQELMKQIDIMVAHKKSE-WEGQTRALETRldireeellsARNTLERKHKEIGLLrQQLEELEKGKQElvAKYEQQL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  366 RKRQLEL-------EKQLEKQRELERQREEERRKEIERREAAKRELE--RQRQLEWERnrrqellnQRNKEQEDIVVLKA 436
Cdd:pfam17045   84 QKLQEELsklkrsyEKLQRKQLKEAREEAKSREEDRSELSRLNGKLEefRQKSLEWEQ--------QRLQYQQQVASLEA 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  437 KKKTLEFELE---------ALNDKKHQLEGKLQDIRcRLTTQRQEIESTNKSRELriaEITHLQQQLQESQQMLGRLIPE 507
Cdd:pfam17045  156 QRKALAEQSSliqsaayqvQLEGRKQCLEASQSEIQ-RLRSKLERAQDSLCAQEL---ELERLRMRVSELGDSNRKLLEE 231

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1061899772  508 KQILNDQLKQVQ-QNSLHRDSLVTLKRALEAKE 539
Cdd:pfam17045  232 QQRLLEELRMSQrQLQVLQNELMELKATLQSQD 264

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212847 [Multi-domain] Cd Length: 59 Bit Score: 45.96 E-value: 2.04e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1061899772  890 LNFNKNDVITVL--EQQDMWWFGEVQG--QKGWFPKSYVK 925
Cdd:cd11914     18 LRFNRGDIITVLvpEARNGWLYGKLEGssRQGWFPEAYVK 57

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 45.97 E-value: 2.07e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  877 QALYPWRAKKDNH-LNFNKNDVITVLEQQD-MWWFGEVQGQKGWFPKSYV 924
Cdd:cd11829      3 RTLYAFTGEQHQQgLSFEAGELIRVLQAPDgGWWEGEKDGLRGWFPASYV 52

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 46.10 E-value: 2.07e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  706 VYYRALYPFESRSHDEITIQPGDIVMVDESQTgEPGWLGGEL-KGKTGWFPANYAE 760
Cdd:cd11998      1 VRVRALYDYDGQEQDELSFKAGDELTKLEDED-EQGWCKGRLdSGQVGLYPANYVE 55

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 45.82 E-value: 2.07e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVM----VDESqtgepgWLGGELKGKTGWFPANYAE 760
Cdd:cd11786      1 CAKALYNYEGKEPGDLSFKKGDIILlrkrIDEN------WYHGECNGKQGFFPASYVQ 52

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 52.25 E-value: 2.19e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKlpvtfEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLE 377
Cdd:COG1196    426 LEEALAELEEE-----EEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAE 500

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  378 KQRELERQREEERRKEIERRE----------------------AAKRELERQRQLEWERNRRQELLNQRNK--------- 426
Cdd:COG1196    501 ADYEGFLEGVKAALLLAGLRGlagavavligveaayeaaleaaLAAALQNIVVEDDEVAAAAIEYLKAAKAgratflpld 580

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  427 --EQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIR--CRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLG 502
Cdd:COG1196    581 kiRARAALAAALARGAIGAAVDLVASDLREADARYYVLGdtLLGRTLVAARLEAALRRAVTLAGRLREVTLEGEGGSAGG 660

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  503 RLIPEKQILNDQLKQVQQN--SLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQ 580
Cdd:COG1196    661 SLTGGSRRELLAALLEAEAelEELAERLAEEELELEEALLAEEEEERELAEAEEERLEEELEEEALEEQLEAEREELLEE 740

                          330       340       350
                   ....*....|....*....|....*....|....*
gi 1061899772  581 QLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRR 615
Cdd:COG1196    741 LLEEEELLEEEALEELPEPPDLEELERELERLERE 775

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212997 Cd Length: 56 Bit Score: 45.88 E-value: 2.23e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQII-NVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd12064      5 ALYACKAEHDSELSFTAGTVFdNVHPSQEPGWLEGTLNGKTGLIPENYVEF 55

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 46.09 E-value: 2.28e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPG-----GWWEGELQARgkkrqIGWFPANYV 1091
Cdd:cd12058      4 ALYDYEASGEDELSLRRGDVVEVLSQDAAvsgddGWWAGKIRHR-----LGIFPANYV 56

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 45.92 E-value: 2.28e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  968 MYTYESSEQGDLTFQQGDVILVTKK---DGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd12142      5 LFDYNPVAPDELALKKGDVIEVISKeteDEGWWEGELNGRRGFFPDNFV 53

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 45.56 E-value: 2.29e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11869      4 ALFDFTGNSKLELNFKAGDVIfLLSRVNKDWLEGTVRGATGIFPLSFVKI 53

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 45.77 E-value: 2.30e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYV 1091
Cdd:cd11902      3 AFVKFAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNG-----QIGWFPSNYV 52

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 45.73 E-value: 2.34e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  876 AQALYPWRAKKD-NHLNFNKNDVITVLEQQDM------WWFGEVQ-GQKGWFPKSYV 924
Cdd:cd11771      2 CRALYDFTPENPeMELSLKKGDIVAVLSKTDPlgrdseWWKGRTRdGRIGWFPSNYV 58

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 45.56 E-value: 2.61e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11869      5 LFDFTGNSKLELNFKAGDVIFLLSRVNKDWLEGTVRGATGIFPLSFVKI 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 45.50 E-value: 2.76e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPS 1164
Cdd:cd11832      1 YFIAVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFPS 48

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 45.37 E-value: 2.77e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYV 924
Cdd:cd11772      4 ALYDYEAQHPDELSFEEGDLLYISDKSDPnWWKATCGGKTGLIPSNYV 51

Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212785 Cd Length: 62 Bit Score: 45.77 E-value: 2.84e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1118 VIGMYDY----TAQNDD---ELAFNKGQIINVLNKEDPD-WWKGEVNG-QVGLFPSNYVK 1168
Cdd:cd11851      2 MVALYDYnpetMSPNDDpeeELSFHAGDVVRVYGPMDEDgFYYGELEGgRKGLVPSNFVQ 61

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 45.47 E-value: 2.86e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVmVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11960      3 RALYDYQAADDTEISFDPGDII-TDIEQIDEGWWRGTGPDGTYGLFPANYVE 53

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 45.36 E-value: 2.88e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVI--LVTKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11882      4 ALYACKAEDESELSFEPGQIItnVQPSDEPGWLEGTLNGRTGLIPENYVEF 54

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 45.18 E-value: 3.05e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYV 1167
Cdd:cd11889      5 VYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKLrrNGAEGIFPSNFV 53

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212721 [Multi-domain] Cd Length: 53 Bit Score: 45.40 E-value: 3.10e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1117 QVIGMYDYTAQNDDE---LAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNY 1166
Cdd:cd11787      1 QCKALYDFEMKDEDEkdcLTFKKGDVITVIRRVDENWAEGRLGDKIGIFPISF 53

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 45.33 E-value: 3.12e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKG--EVNGQVGLFPSNYV 1167
Cdd:cd11918      7 VYQYRPQNEDELELREGDRVDVMQQCDDGWFVGvsRRTQKFGTFPGNYV 55

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 45.38 E-value: 3.29e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  962 GEEFIAMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTV--GDKAGVFPSNYV 1013
Cdd:cd11933      1 GKSFRAMYDYRAADDDEVSFKDGDTIVnVQTIDEGWMYGTVqrTGKTGMLPANYV 55

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 45.27 E-value: 3.36e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYVK 1092
Cdd:cd12052      8 YKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRR-----GLFPDNFVR 52

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 45.40 E-value: 3.38e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKD--GDWWTG-TVGDKAGVFPSNYV 1013
Cdd:cd11763      4 ALYDFDSQPSGELSLRAGEVLTITRQDvgDGWLEGrNSRGEVGLFPSSYV 53

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 45.19 E-value: 3.44e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKG-EVNGQVGLFPSNYV 1167
Cdd:cd11905      3 VVAMYDFQPTEPHDLRLETGEEYVILEKNDVHWWKArDKYGKEGYIPSNYV 53

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 45.36 E-value: 3.50e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESqtgEPGWLGGELKGKTGWFPANY 758
Cdd:cd11991      2 YVAMYTYESNEQGDLTFQQGDVILVTKK---DGDWWTGTVGDKTGVFPSNY 49

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 51.66 E-value: 3.50e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  288 VDQRLPEEPVLEDEQQQlEKKLPVTFEDKKR-ENFERGNLE-LEKRRQALLEQQRKEQERLAQlERAEQERKERERQEQ- 364
Cdd:PTZ00266   430 VDKDHAERARIEKENAH-RKALEMKILEKKRiERLEREERErLERERMERIERERLERERLER-ERLERDRLERDRLDRl 507

                           90
                   ....*....|....*
gi 1061899772  365 ERKRQLELEK-QLEK 378
Cdd:PTZ00266   508 ERERVDRLERdRLEK 522

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 45.32 E-value: 3.53e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1043 YTATGPEQLTLAPGQLI-LIRKKNPGGWWEGELQARgkkrqIGWFPANYVK 1092
Cdd:cd11976      8 FCARDRSELSLKEGDIIkILNKKGQQGWWRGEIYGR-----VGWFPANYVE 53

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 45.06 E-value: 3.71e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKDGD----WWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11807      5 ALFDYEAENGDELSFREGDELTVLRKGDDdeteWWWARLNDKEGYVPRNLLGL 57

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 51.60 E-value: 3.77e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  297 VLEDEQQQLEKKLPVtfEDKKRENFERGNLELEKRRQAL----------LEQQRKEQERL-AQLERAEqERKERERQEQE 365
Cdd:TIGR02168  348 ELKEELESLEAELEE--LEAELEELESRLEELEEQLETLrskvaqlelqIASLNNEIERLeARLERLE-DRRERLQQEIE 424

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  366 RKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQR-QLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFE 444
Cdd:TIGR02168  425 ELLKKLEEAELKELQAELEELEEELEELQEELERLEEALEELReELEEAEQALDAAERELAQLQARLDSLERLQENLEGF 504

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  445 LEAL-NDKKHQ---------------------------LEGKLQDIRCR-LTTQRQEIESTNKSRELRIA---------- 485
Cdd:TIGR02168  505 SEGVkALLKNQsglsgilgvlselisvdegyeaaieaaLGGRLQAVVVEnLNAAKKAIAFLKQNELGRVTflpldsikgt 584

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  486 --EITHLQQQLQESQQMLGRLIPEKQ------ILNDQLKQV-----------QQNSLHRD-SLVTLK-----------RA 534
Cdd:TIGR02168  585 eiQGNDREILKNIEGFLGVAKDLVKFdpklrkALSYLLGGVlvvddldnaleLAKKLRPGyRIVTLDgdlvrpggvitGG 664

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  535 LEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELReihnKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQR 614
Cdd:TIGR02168  665 SAKTNSSILERRREIEELEEKIEELEEKIAELEKALAELR----KELEELEEELEQLRKELEELSRQISALRKDLARLEA 740

                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  615 RAQERDKQWlehVQQEDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRL 671
Cdd:TIGR02168  741 EVEQLEERI---AQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQL 794

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 45.19 E-value: 3.86e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVDESQTgEPGWLGGELKGKTGWFPANY 758
Cdd:cd11948      4 ALYSFQATESDELPFQKGDILKILNMED-DQNWYKAELQGREGYIPKNY 51

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 45.20 E-value: 3.87e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1121 MYDYTA-QNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11829      5 LYAFTGeQHQQGLSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 52

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 45.08 E-value: 3.94e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772 1036 IAQVIASYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELqaRGkkrQIGWFPANYVK 1092
Cdd:cd11841      1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSqfDWWEGRL--RG---RVGIFPANYVS 54

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); MPP1, also called 55 kDa erythrocyte membrane protein (p55), is a ubiquitously-expressed scaffolding protein that plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. It was originally identified as an erythrocyte protein that stabilizes the actin cytoskeleton to the plasma membrane by forming a complex with 4.1R protein and glycophorin C. MPP1 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains the three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213013 Cd Length: 62 Bit Score: 45.33 E-value: 3.94e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1120 GMYDYTAQNDD-------ELAFNKGQIINVLNKEDPDWWKGEVNGQ----VGLFPS 1164
Cdd:cd12080      4 AQFDYDPKKDNlipckeaGLKFQTGDIIQIINKDDSNWWQGRVEGSgeesAGLIPS 59

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 45.15 E-value: 3.96e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELK--GKTGWFPANYAEK 761
Cdd:cd11785      2 YRVIVPYPPQSEAELELKEGDIVFVHKKR--EDGWFKGTLQrtGKTGLFPGSFVES 55

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 45.27 E-value: 4.02e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKN--PGGWWEGELQARGkkrqiGWFPANYVKLL 1094
Cdd:cd12057      3 KVLFPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGRR-----GVFPDNFVKLL 56

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212998 [Multi-domain] Cd Length: 54 Bit Score: 44.98 E-value: 4.05e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1121 MYDYTAQNDDELAFNKGQII-NVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd12065      5 VYPCEAEHSSELSFEVGAIFeDVTLSREPGWLEGTLNGKRGLIPENYVEI 54

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins in this family are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.

Pssm-ID: 464768 [Multi-domain] Cd Length: 374 Bit Score: 50.42 E-value: 4.06e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  300 DEQQQLEKKLPVTFEDKKRENF----ERGNLELEKRRQAL-LEQQRKEQERLAQLERAEQERKER-ERQEQERKRQLELE 373
Cdd:pfam15558   35 EELRRRDQKRQETLERERRLLLqqsqEQWQAEKEQRKARLgREERRRADRREKQVIEKESRWREQaEDQENQRQEKLERA 114

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  374 KQLEKQRelerqreeerrkeierreaaKRELERQ-RQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEF--ELEALND 450
Cdd:pfam15558  115 RQEAEQR--------------------KQCQEQRlKEKEEELQALREQNSLQLQERLEEACHKRQLKEREEqkKVQENNL 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  451 K---KHQLegKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDS 527
Cdd:pfam15558  175 SellNHQA--RKVLVDCQAKAEELLRRLSLEQSLQRSQENYEQLVEERHRELREKAQKEEEQFQRAKWRAEEKEEERQEH 252

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  528 lvtlKRAL-EAKELARQHLRDQLDEVEKETRSKLQEIdifnNQLKELREIHNKQQLQKQKSMEAERLKQ--KEQERKIIE 604
Cdd:pfam15558  253 ----KEALaELADRKIQQARQVAHKTVQDKAQRAREL----NLEREKNHHILKLKVEKEEKCHREGIKEaiKKKEQRSEQ 324

                          330
                   ....*....|...
gi 1061899772  605 LEKQKEEAQRRAQ 617
Cdd:pfam15558  325 ISREKEATLEEAR 337

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 51.19 E-value: 4.06e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  290 QRLPEEPVLEDEQQQLEKKLPVTFedKKRENFERgnlELEKRRQALLEQQRKEQERLAQ--LERAEQERKERERQEQERK 367
Cdd:PRK02224   248 ERREELETLEAEIEDLRETIAETE--REREELAE---EVRDLRERLEELEEERDDLLAEagLDDADAEAVEARREELEDR 322

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  368 RQlELEKQLEKQRELERQREEErrkeierreaAKRELERQRQLEwerNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEA 447
Cdd:PRK02224   323 DE-ELRDRLEECRVAAQAHNEE----------AESLREDADDLE---ERAEELREEAAELESELEEAREAVEDRREEIEE 388

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  448 LNDKKHQLEGKLQDIrcrlTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLK-----QVQQNS 522
Cdd:PRK02224   389 LEEEIEELRERFGDA----PVDLGNAEDFLEELREERDELREREAELEATLRTARERVEEAEALLEAGKcpecgQPVEGS 464

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  523 LHRDSLVTLKRALEAKELARQHLRDQLDEVEKETrsklqeidifnNQLKELREIHNK-QQLQKQKSMEAERLKQK----- 596
Cdd:PRK02224   465 PHVETIEEDRERVEELEAELEDLEEEVEEVEERL-----------ERAEDLVEAEDRiERLEERREDLEELIAERretie 533

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  597 EQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEK--LKRE-ESVKKKDGEEKGKQEAQDKLGRL 671
Cdd:PRK02224   534 EKRERAEELRERAAELEAEAEEKREAAAEAEEEAEEAREEVAELNSKLaeLKERiESLERIRTLLAAIADAEDEIERL 611

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 45.02 E-value: 4.24e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKkrqIGWFPANYVKL 1093
Cdd:cd11874      2 CKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKL--NGK---VGVFPSNFVKE 53

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 51.21 E-value: 4.28e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  288 VDQRLPEEPVLEDEQQQLEKKLPVTFEDKKRENFERGnlELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERK 367
Cdd:TIGR02168  749 IAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIE--ELEAQIEQLKEELKALREALDELRAELTLLNEEAANLRERL 826

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  368 RQLELEKQLEKQRELERQREEERRKEIERREAAKRElERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEA 447
Cdd:TIGR02168  827 ESLERRIAATERRLEDLEEQIEELSEDIESLAAEIE-ELEELIEELESELEALLNERASLEEALALLRSELEELSEELRE 905

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1061899772  448 LNDKKHQLEGKLQDIRCRLTTQRQEIESTnksrELRIAEI 487
Cdd:TIGR02168  906 LESKRSELRRELEELREKLAQLELRLEGL----EVRIDNL 941

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 45.05 E-value: 4.49e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTK-KDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11974      5 ALWDHVTMDDQELAFKAGDVIRVLEaSNKDWWWGRNEDREAWFPASFVRL 54

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

Pssm-ID: 405931 [Multi-domain] Cd Length: 151 Bit Score: 47.74 E-value: 4.55e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  550 DEVEKETRSKLQEI-DIFNNQLKELREIHNKQQLQKQKSM-EAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHV 627
Cdd:pfam15346   33 DEIEAEVERRVEEArKIMEKQVLEELEREREAELEEERRKeEEERKKREELERILEENNRKIEEAQRKEAEERLAMLEEQ 112

                           90       100
                   ....*....|....*....|....
gi 1061899772  628 QQEDEHQRPRKLHEEEKLKREESV 651
Cdd:pfam15346  113 RRMKEERQRREKEEEEREKREQQK 136

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 44.83 E-value: 4.56e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELqarGKKRQIgWFPANYVK 1092
Cdd:cd11969      8 YRAKRSDELSFCKGALIHNVSKETGGWWKGDY---GGKVQH-YFPSNYVE 53

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 45.01 E-value: 4.62e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK----DGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11954      5 ALWDYEAQNADELSFQEGDAITILRRkddsETEWWWARLNDKEGYVPKNLLGL 57

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 44.83 E-value: 4.80e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  712 YPFESRSHDEITIQPGDIVMvDESQTGEPGWLGGELKGKTGWFPANYAEKI 762
Cdd:cd12053      6 YDYDAVHEDELTIRVGEIIR-NVKKLEEEGWLEGELNGRRGMFPDNFVKEI 55

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 44.93 E-value: 4.90e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGD--WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11830      3 KARYDFCARDMRELSLKEGDVVKIYNKKGQqgWWRGEINGRIGWFPSTYV 52

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 44.98 E-value: 5.07e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQ--VGLFPSNYVK 1168
Cdd:cd11917     10 LYNYMPRNEDELELREGDVIDVMEKCDDGWFVGTSRRTkfFGTFPGNYVK 59

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 44.99 E-value: 5.09e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772  880 YPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11902      7 FAYVAEREDELSLVKGSRVTVMEKcSDGWWRGSYNGQIGWFPSNYV 52

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 49.15 E-value: 5.18e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  525 RDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREihNKQQLQKQKSMEAERLKQKEQERKIIE 604
Cdd:COG1579     37 EDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEARIKKYEEQLGNVRN--NKEYEALQKEIESLKRRISDLEDEILE 114

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772  605 LEKQKEEAQRRAQERDKQwLEHVQQEDEHQRPRKLHEEEKLKREE 649
Cdd:COG1579    115 LMERIEELEEELAELEAE-LAELEAELEEKKAELDEELAELEAEL 158

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 44.70 E-value: 5.21e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQ-----DMWWFGEVQGQKGWFP 920
Cdd:cd11762      2 VRALYDYEAQSDEELSFPEGAIIRILRKDdngvdDGWWEGEFNGRVGVFP 51

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 44.66 E-value: 5.25e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTGTV-GDKAGVFPSNYVRL 1015
Cdd:cd11837      3 TALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELeGGEEGWFPKSYVKE 53

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 44.64 E-value: 5.48e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd12076      5 VIYPYTARDQDEINLEKGAVVEVIQKNlEGWWKIRYQGKEGWAPASYLK 53

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 44.62 E-value: 5.59e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  874 LQAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 927
Cdd:cd11920      1 LPARAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYeGEHHGRVGIFPISYVEKL 55

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 44.64 E-value: 5.62e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQG-----QKGWFPKSYV 924
Cdd:cd11887      6 ALYPYESDHEDDLNFDVGQLITVTEEEDAdWYFGEYVDsngntKEGIFPKNFV 58

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 44.69 E-value: 5.69e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKK--DGdWWTGT--VGDKAGVFPSNYV 1013
Cdd:cd11783      2 YVALYPYKPQKPDELELRKGEMYTVTEKcqDG-WFKGTslRTGQSGVFPGNYV 53

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 44.55 E-value: 6.01e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMV-DESQTgepGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11985      2 YVALYKFLPQENNDLPLQPGDRVMVvDDSNE---DWWKGKSGDRVGFFPANFVQR 53

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 44.41 E-value: 6.20e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd12046      1 QVVALFSYEASQPEDLEFQKGDVILVLSKvNEDWLEGQCKGKIGIFPSAFVE 52

Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212946 Cd Length: 61 Bit Score: 44.68 E-value: 6.39e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1117 QVIGMYDYTAQ----NDD---ELAFNKGQIINVLNKEDPD-WWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12013      1 RMVALFDYDPResspNVDaevELSFRAGDIITVFGEMDEDgFYYGELNGQRGLVPSNFLE 60

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 45.01 E-value: 6.75e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11973     22 ALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRVLDSEGWFPASFVRL 71

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 45.01 E-value: 6.89e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11973     20 AEALWDHVTMDDQELGFKAGDVIEVMDATNKeWWWGRVLDSEGWFPASFVRL 71

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 50.40 E-value: 7.06e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLpvtfeDKKRENFERGNLELEKRRQALL---EQQRKEQERLA----QLERAEQERKERERQEQERKRQL 370
Cdd:TIGR04523  223 LKKQNNQLKDNI-----EKKQQEINEKTTEISNTQTQLNqlkDEQNKIKKQLSekqkELEQNNKKIKELEKQLNQLKSEI 297

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  371 -------------ELEKQLEKQRELERQREEERRKEIERREAAKREL---------------ERQRQLEWERNRRQELLN 422
Cdd:TIGR04523  298 sdlnnqkeqdwnkELKSELKNQEKKLEEIQNQISQNNKIISQLNEQIsqlkkeltnsesensEKQRELEEKQNEIEKLKK 377

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  423 QRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEIThlqqqlqesqqmlg 502
Cdd:TIGR04523  378 ENQSYKQEIKNLESQINDLESKIQNQEKLNQQKDEQIKKLQQEKELLEKEIERLKETIIKNNSEIK-------------- 443

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  503 RLIPEKQILNDQLKQVQQnslHRDSlvtLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREihNKQQL 582
Cdd:TIGR04523  444 DLTNQDSVKELIIKNLDN---TRES---LETQLKVLSRSINKIKQNLEQKQKELKSKEKELKKLNEEKKELEE--KVKDL 515

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  583 QKQKSMEAERLKQ-----KEQERKIIELEKQKEEAQrraQERDKQWLEHVQQEDEhQRPRKLHEEEK 644
Cdd:TIGR04523  516 TKKISSLKEKIEKlesekKEKESKISDLEDELNKDD---FELKKENLEKEIDEKN-KEIEELKQTQK 578

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 48.77 E-value: 7.34e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  414 RNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEithlqqq 493
Cdd:COG1579     23 EHRLKELPAELAELEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEARIKKYEEQLGNVRNNKEYEALQ------- 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  494 lqesqqmlgrlipeKQIlnDQLKQvqQNSLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKEL 573
Cdd:COG1579     96 --------------KEI--ESLKR--RISDLEDEILELMERIEELEEELAELEAELAELEAELEEKKAELDEELAELEAE 157

                          170       180
                   ....*....|....*....|....*...
gi 1061899772  574 REIHNKQQLQKQKSMEAERLKQKEQERK 601
Cdd:COG1579    158 LEELEAEREELAAKIPPELLALYERIRK 185

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 44.12 E-value: 7.82e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDEsqTGEPGWLGGELKGKTGWFPANYAEKI 762
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLG--KDNDGWWEGETGGRVGLVPSTAVEEI 54

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 44.43 E-value: 7.83e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPG-----GWWEGELQARgkkrqIGWFPANYV 1091
Cdd:cd11876      8 YDARGEDELTLRRGQPVEVLSKDAAvsgdeGWWTGKIGDK-----VGIFPSNYV 56

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 44.22 E-value: 8.48e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  874 LQAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 925
Cdd:cd12060      2 LVVKARFNFKQTNEDELSVCKGDIIYVTRVEEGgWWEGTLNGKTGWFPSNYVR 54

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 43.95 E-value: 8.68e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11842      1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANYVE 54

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 43.92 E-value: 9.03e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQarGKKrqiGWFPANYV 1091
Cdd:cd11806      4 AIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHN--GCC---GYIPASHL 51

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 50.07 E-value: 9.30e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLP------VTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERA------EQERKErerqEQE 365
Cdd:TIGR02169  249 LEEELEKLTEEISelekrlEEIEQLLEELNKKIKDLGEEEQLRVKEKIGELEAEIASLERSiaekerELEDAE----ERL 324

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  366 RKRQLELEKQLEKqrelerqreeerrkeierREAAKRELERQR----QLEWE----RNRRQELLNQRNKEQEDIVVLKAK 437
Cdd:TIGR02169  325 AKLEAEIDKLLAE------------------IEELEREIEEERkrrdKLTEEyaelKEELEDLRAELEEVDKEFAETRDE 386

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  438 KKTLEFELEALNDKKHQLEG---KLQDIRCRLTTQRQEIESTNKSRELRIAEithlqqqlqesqqmlgrLIPEKQILNDQ 514
Cdd:TIGR02169  387 LKDYREKLEKLKREINELKReldRLQEELQRLSEELADLNAAIAGIEAKINE-----------------LEEEKEDKALE 449

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  515 LKQVQQNslhrdsLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELRE 575
Cdd:TIGR02169  450 IKKQEWK------LEQLAADLSKYEQELYDLKEEYDRVEKELSKLQRELAEAEAQARASEE 504

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 44.01 E-value: 9.50e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSY 923
Cdd:cd11817      2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAeWSRGRLNGREGIFPRAF 50

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 43.89 E-value: 9.54e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKN--PGGWWEGELqaRGKkrqIGWFPANYV 1091
Cdd:cd11836      3 RALYAFEARNPDEISFQPGDIIQVDESQvaEPGWLAGEL--KGK---TGWFPANYV 53

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity to GRAF and GRAF2. It contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212999 Cd Length: 55 Bit Score: 43.90 E-value: 9.63e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQII-NVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd12066      1 QAKAMYSCKAEHSHELSFPQGAIFsNVYPSVEPGWLKATYEGKTGLVPENYV 52

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212859 [Multi-domain] Cd Length: 55 Bit Score: 44.19 E-value: 9.68e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYV 1167
Cdd:cd11926      3 VAIYPYTPRKEDELELRKGEMFLVFERCQDGWFKGTSmhTSKIGVFPGNYV 53

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 44.24 E-value: 9.86e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11971      3 VAIYDYSKDKDDELSFMEGAIIYVIKKNDDgWYEGVCNGVTGLFPGNYV 51

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 44.21 E-value: 9.87e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTGT--VGDKAGVFPSNYV 1013
Cdd:cd12004      3 VALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARslTTKKEGFIPSNYV 52

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 44.03 E-value: 1.00e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  706 VYYrALYPFESRSHDEITIQPGDIVMVDE--SQTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd12141      1 VYY-AVYTFKARSPNELSVSANQRVRILEfsDLTGNKEWWLAEANGQKGYVPSNYIRK 57

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 43.87 E-value: 1.05e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  874 LQAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11901      2 LPAYVKFNYTAEREDELSLVKGTKVIVMEKcSDGWWRGSYNGQVGWFPSNYV 53

Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212736 [Multi-domain] Cd Length: 52 Bit Score: 43.82 E-value: 1.06e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM---WWFGEVQGQKGWFPKSY 923
Cdd:cd11802      1 KARVLYDYDAEDSTELSLLADEVITVYELPGMdedYMMGERGSQRGKVPVAY 52

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 43.79 E-value: 1.08e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVIT-VLEQQDMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd11873      4 VEFDYDAEEPDELTLKVGDIITnVKKMEEGWWEGTLNGKRGMFPDNFVK 52

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 43.85 E-value: 1.10e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1061899772 1124 YTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11982      9 YQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVGWFPSDCV 52

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 43.63 E-value: 1.11e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGE-VQGQKGWFPKSYVKL 926
Cdd:cd11962      2 AVVLYDYEKDEDNEIELVEGEIVTNIEMVDEdWWMGTnSKGESGLFPSNYVEL 54

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212829 [Multi-domain] Cd Length: 55 Bit Score: 43.80 E-value: 1.12e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  709 RALYPFESRSHDEITIQPG-DIVMVDESQTGepGWLGGE-LKGKTGWFPANYAE 760
Cdd:cd11896      3 RALYSFQSENKEEINIQENeELVIFSENSLD--GWLQGQnSRGETGLFPASYVE 54

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212980 Cd Length: 53 Bit Score: 43.65 E-value: 1.13e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd12047      3 VAQHDYSAQGPEDLEFSQGDTIdILSEVNQEWLEGHCDGRIGIFPKCFA 51

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 43.55 E-value: 1.14e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11816      3 VARFDFEGEQEDELSFSEGDVITLKEYVGEeWAKGELNGKIGIFPLNFV 51

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 49.13 E-value: 1.16e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  416 RRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQ 495
Cdd:COG4372     11 ARLSLFGLRPKTGILIAALSEQLRKALFELDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNEQLQ 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  496 ESQQMLGRLIPEKQILNDQLKQVQQnslhrdSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELRE 575
Cdd:COG4372     91 AAQAELAQAQEELESLQEEAEELQE------ELEELQKERQDLEQQRKQLEAQIAELQSEIAEREEELKELEEQLESLQE 164

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  576 IHNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEE 643
Cdd:COG4372    165 ELAALEQELQALSEAEAEQALDELLKEANRNAEKEEELAEAEKLIESLPRELAEELLEAKDSLEAKLG 232

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 43.63 E-value: 1.16e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGD-KAGVFPSNYVRL 1015
Cdd:cd11962      3 VVLYDYEKDEDNEIELVEGEIVTnIEMVDEDWWMGTNSKgESGLFPSNYVEL 54

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 43.76 E-value: 1.17e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAEKI 762
Cdd:cd11921      4 RLKFDFQAQSPKELTLQKGDIVYIHKEV--DKNWLEGEHHGRVGIFPANYVEVL 55

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 43.86 E-value: 1.20e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQ--DMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd11978      3 AIARYDFCARDMRELSLLKGDVVKIYTKMstNGWWRGEVNGRVGWFPSTYVE 54

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 43.53 E-value: 1.23e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd11841      4 ALYSFEGQQPCDLSFQAGDRITVLTRTDSQFDWWEGRLRGRVGIFPANY 52

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 43.93 E-value: 1.25e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1036 IAQVIASYTATGPEQLTLAPGQLI-LIRKKNPG---GWWEGELQARgkkrqIGWFPA 1088
Cdd:cd11762      1 LVRALYDYEAQSDEELSFPEGAIIrILRKDDNGvddGWWEGEFNGR-----VGVFPS 52

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 49.75 E-value: 1.32e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  270 SFRRVRSGSGISVISSTSVDQRLPEEPVLEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQAllEQQRKEQerlaQL 349
Cdd:PTZ00121  1579 ALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEA--EEKKKAE----EL 1652

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  350 ERAEQERKERerQEQERKRQlELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLnQRNKEQE 429
Cdd:PTZ00121  1653 KKAEEENKIK--AAEEAKKA-EEDKKKAEEAKKAEEDEKKAAEALKKEAEEAKKAEELKKKEAEEKKKAEEL-KKAEEEN 1728

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  430 DIVVLKAKKKTLEFELEALNDKKHqlEGKLQDIRCRLTTQRQEIESTNKSRELRIAEithlqqqLQESQQMLGRLIPEKQ 509
Cdd:PTZ00121  1729 KIKAEEAKKEAEEDKKKAEEAKKD--EEEKKKIAHLKKEEEKKAEEIRKEKEAVIEE-------ELDEEDEKRRMEVDKK 1799

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  510 I--LNDQLKQVQQNSLHRDSLVTLKRAL---EAKELA--RQHLRDQLDEVEKETRSK--------------LQEIDIFNN 568
Cdd:PTZ00121  1800 IkdIFDNFANIIEGGKEGNLVINDSKEMedsAIKEVAdsKNMQLEEADAFEKHKFNKnnengedgnkeadfNKEKDLKED 1879

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  569 QLKELREIHNKQQLQKQkSMEAERLKQ--KEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQED 631
Cdd:PTZ00121  1880 DEEEIEEADEIEKIDKD-DIEREIPNNnmAGKNNDIIDDKLDKDEYIKRDAEETREEIIKISKKD 1943

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212954 [Multi-domain] Cd Length: 53 Bit Score: 43.41 E-value: 1.32e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  708 YRALYPFESRSHDEITIQPGDivMVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd12021      2 YRAIADYEKSSKSEMALKTGD--VVEVVEKSENGWWFCQLKAKRGWVPASYLE 52

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 43.78 E-value: 1.38e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQ------DMWWFGEVQGQKGWFPKSYV 924
Cdd:cd12058      4 ALYDYEASGEDELSLRRGDVVEVLSQDaavsgdDGWWAGKIRHRLGIFPANYV 56

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 49.53 E-value: 1.42e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  330 KRRQALLEQQRKE-QERLAQLERAEQERKERERQEQERKRQLE-LEKQLEKQrelerqreeerrkeiERREAAKRELERQ 407
Cdd:COG4913    609 RAKLAALEAELAElEEELAEAEERLEALEAELDALQERREALQrLAEYSWDE---------------IDVASAEREIAEL 673

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  408 RQlewernRRQELLnqrnKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIEstnksRELRIAEI 487
Cdd:COG4913    674 EA------ELERLD----ASSDDLAALEEQLEELEAELEELEEELDELKGEIGRLEKELEQAEEELD-----ELQDRLEA 738

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  488 THLQQQLQESQQMLGRLipeKQILNDQLKQVQQNSLHRDslvtLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFN 567
Cdd:COG4913    739 AEDLARLELRALLEERF---AAALGDAVERELRENLEER----IDALRARLNRAEEELERAMRAFNREWPAETADLDADL 811

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  568 NQLKELREIHNkqQLQKQKSMEAE----RLKQKEQERKIIELEKQKEEAQRRAQER 619
Cdd:COG4913    812 ESLPEYLALLD--RLEEDGLPEYEerfkELLNENSIEFVADLLSKLRRAIREIKER 865

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein A; UBASH3A is also called Cbl-Interacting Protein 4 (CLIP4), T cell Ubiquitin LigAnd (TULA), or T cell receptor Signaling (STS)-2. It is only found in lymphoid cells and exhibits weak phosphatase activity. UBASH3A facilitates T cell-induced apoptosis through interaction with the apoptosis-inducing factor AIF. It is involved in regulating the level of phosphorylation of the zeta-associated protein (ZAP)-70 tyrosine kinase. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212870 [Multi-domain] Cd Length: 60 Bit Score: 43.85 E-value: 1.46e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGE--PGWLGG--ELKGKTGWFPANYAEK 761
Cdd:cd11937      4 RALFQYKPQNIDELMLSPGDYIFVDPTQQSEasEGWVIGisHRTGCRGFLPENYTER 60

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 43.39 E-value: 1.53e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1043 YTATGPEQLTLAPGQLILI-RKKNPGGWWEGELQARgkkrqIGWFPANYVK 1092
Cdd:cd11830      8 FCARDMRELSLKEGDVVKIyNKKGQQGWWRGEINGR-----IGWFPSTYVE 53

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 43.60 E-value: 1.53e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772  880 YPWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd12016      7 QAYKAENEDEIGFETGVVVEVIQKNlDGWWKIRYQGKEGWAPATYLK 53

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 43.39 E-value: 1.55e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 925
Cdd:cd11856      4 AIADYEAQGDDEISLQEGEVVEVLEKNDSgWWYVRKGDKEGWVPASYLE 52

Src Homology 3 domain of SH3 domain-binding protein 4; SH3 domain-binding protein 4 (SH3BP4) is also called transferrin receptor trafficking protein (TTP). SH3BP4 is an endocytic accessory protein that interacts with endocytic proteins including clathrin and dynamin, and regulates the internalization of the transferrin receptor (TfR). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212691 Cd Length: 52 Bit Score: 43.47 E-value: 1.59e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11757      1 EVVAIKDYCPTNFTTLKFSKGDHLYVLDTSGGEWWYAHNTTEMGYIPSSYVQ 52

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 49.35 E-value: 1.61e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  301 EQQQLEKKLPVTFEDKKRENFERGNLE-LEKRR-------QALLEQQRKEQERLAQLERAEQERKERERQEQERK 367
Cdd:PTZ00266   451 EMKILEKKRIERLEREERERLERERMErIERERlererleRERLERDRLERDRLDRLERERVDRLERDRLEKARR 525

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1, also called Insulin Receptor Tyrosine Kinase Substrate (IRTKS); BAIAP2L1 or IRTKS is widely expressed, serves as a substrate for the insulin receptor, and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. IRTKS mediates the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRTKS has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212846 Cd Length: 58 Bit Score: 43.37 E-value: 1.62e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1061899772  890 LNFNKNDVITVL--EQQDMWWFGE--VQGQKGWFPKSYVKL 926
Cdd:cd11913     18 LSFAQGDVITLLipEEKDGWLYGEhdTTKARGWFPSSYTRP 58

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 43.48 E-value: 1.64e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  966 IAMYTYESSEQgdLTFQQGDVILVTKKDGD-WWTGTV---GDK--AGVFPSNYVRL 1015
Cdd:cd11839      5 IAPFTATAENQ--LSLAVGQLVLVRKKSPSgWWEGELqarGKKrqIGWFPANYVKL 58

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 43.44 E-value: 1.64e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLnKEDPDWWKGE--VNGQVGLFPSNYV 1167
Cdd:cd12004      2 VVALYPYDGIHEDDLSFKKGEKLKVI-EEHGEWWKARslTTKKEGFIPSNYV 52

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 43.42 E-value: 1.72e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1037 AQVIASYTATGPE-QLTLAPGQLILIRKK-----NPGGWWEGelqaRGKKRQIGWFPANYV 1091
Cdd:cd11771      2 CRALYDFTPENPEmELSLKKGDIVAVLSKtdplgRDSEWWKG----RTRDGRIGWFPSNYV 58

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 49.01 E-value: 1.75e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  535 LEAKELArQHLRDqldEVEKETRSKLQEIDIFNNQLKElRE--IHNKQQLQKQKSMEAERlKQKEQERKIIELEKQKEEA 612
Cdd:PRK12704    60 LEAKEEI-HKLRN---EFEKELRERRNELQKLEKRLLQ-KEenLDRKLELLEKREEELEK-KEKELEQKQQELEKKEEEL 133

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  613 QRRAQERDK---------------QWLEHVQQEDEHQRPRKLHEEEKLKREES 650
Cdd:PRK12704   134 EELIEEQLQelerisgltaeeakeILLEKVEEEARHEAAVLIKEIEEEAKEEA 186

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 43.47 E-value: 1.78e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGD--WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11978      4 IARYDFCARDMRELSLLKGDVVKIYTKMSTngWWRGEVNGRVGWFPSTYV 53

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 43.06 E-value: 1.99e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVG--DKAGVFPSNYV 1013
Cdd:cd11780      2 YRALYSYTPQNEDELELREGDIVYVMEKCDDgWFVGTSErtGLFGTFPGNYV 53

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. ITK is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, ITK plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, ITK is crucial for the development of T-helper(Th)2 effector responses. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212841 [Multi-domain] Cd Length: 56 Bit Score: 43.08 E-value: 2.03e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWK-GEVNGQVGLFPSNYV 1167
Cdd:cd11908      3 VIALYDYQTNDPQELALRYNEEYHLLDSSEIHWWRvQDKNGHEGYVPSSYL 53

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 48.81 E-value: 2.04e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  286 TSVDQRLPEE-PVLEDEQQQLEKKLPVTFEDKK------RENFERGNLELEKRRQALLEQQRKEQErlaQLERAEQERKE 358
Cdd:TIGR00618  576 TQCDNRSKEDiPNLQNITVRLQDLTEKLSEAEDmlaceqHALLRKLQPEQDLQDVRLHLQQCSQEL---ALKLTALHALQ 652

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  359 RERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWeRNRRQELLNQRNKEQEDIVVLKAKK 438
Cdd:TIGR00618  653 LTLTQERVREHALSIRVLPKELLASRQLALQKMQSEKEQLTYWKEMLAQCQTLL-RELETHIEEYDREFNEIENASSSLG 731

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  439 KTLEFELEALNdkkhQLEGKLQDIRcRLTTQRQEIESTNKSRELRIAEIT-HLQQQLQESQQMLGRLIPEKQILNDQLK- 516
Cdd:TIGR00618  732 SDLAAREDALN----QSLKELMHQA-RTVLKARTEAHFNNNEEVTAALQTgAELSHLAAEIQFFNRLREEDTHLLKTLEa 806

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  517 QVQQNSLHRDSLVTLKRALEAKELArqhlrdQLDEVEKETRSKLQEIDifnNQLKELREihNKQQLQkQKSMEAERLKQK 596
Cdd:TIGR00618  807 EIGQEIPSDEDILNLQCETLVQEEE------QFLSRLEEKSATLGEIT---HQLLKYEE--CSKQLA-QLTQEQAKIIQL 874


                   ...
gi 1061899772  597 EQE 599
Cdd:TIGR00618  875 SDK 877

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 43.09 E-value: 2.06e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  874 LQAQALYPWRAKKDNHLNFNKNDVITVL--EQQDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11946      1 MEAIAKYDFKATADDELSFKRGDILKVLneECDQNWYKAELNGKDGFIPKNYIEM 55

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212934 Cd Length: 68 Bit Score: 43.49 E-value: 2.09e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQ----DMWWFGEVQGQKGWFPKSYVKLISG 929
Cdd:cd12001      5 AKALYDNVAESPDELSFRKGDIMTVLERDtqglDGWWLCSLHGRQGIVPGNRLKILVG 62

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 43.06 E-value: 2.16e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11987      4 ALYPFEARSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 54

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 43.03 E-value: 2.19e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNG--QVGLFPSNYVKL 1169
Cdd:cd11924      2 EAVAQYTFKGDLEVELSFRKGEHICLIRKVNENWYEGRITGtgRQGIFPASYVQV 56

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 42.97 E-value: 2.28e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  707 YYRALYPFESRSHDEITIQPGD-IVMVDESQTgepGWLGGELKGKTGWFPANY 758
Cdd:cd11986      1 YFVALYRFKALEKDDLDFHPGErITVIDDSNE---EWWRGKIGEKTGYFPMNF 50

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 43.03 E-value: 2.28e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAEKI 762
Cdd:cd12054      4 KVLFEYVPQNEDELELKVGDIIDINEEV--EEGWWSGTLNGKSGLFPSNFVKEL 55

Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); MPP6, also called Veli-associated MAGUK 1 (VAM-1) or PALS2, is a scaffolding protein that binds to Veli-1, a homolog of Caenorhabditis Lin-7. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212971 Cd Length: 61 Bit Score: 43.13 E-value: 2.30e-05

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1061899772 1132 LAFNKGQIINVLNKEDPDWWKG---EVNGQVGLFPSNYV 1167
Cdd:cd12038     23 LKFSKGEILQIVNREDPNWWQAshvKEGGSAGLIPSQFL 61

Src Homology 3 domain of the p85 regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212710 Cd Length: 72 Bit Score: 43.65 E-value: 2.36e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVD-------------ESQTGEPGWLGG--ELKGKTGWFPANYAE 760
Cdd:cd11776      3 YRALYDYEKERDEDIILKTGDVLVVEnpellalgvpdgkETVPKPEGWLEGknERTGERGDFPGTYVE 70

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 42.73 E-value: 2.36e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVL-EQQDMWWF-GEVQGQKGWFPKSYV 924
Cdd:cd11804      1 EAVAKHDFKATAEDELSFKKGSILKVLnMEDDPNWYkAELDGKEGLIPKNYI 52

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 43.05 E-value: 2.61e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGDKAGV-FPSNYV 1013
Cdd:cd11970      8 ALFDYKAQREDELTFTKNAIIQnVEKQEGGWWRGDYGGKKQLwFPSNYV 56

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 42.65 E-value: 2.64e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  968 MYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd12054      6 LFEYVPQNEDELELKVGDIIDINEEvEEGWWSGTLNGKSGLFPSNFVK 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 42.69 E-value: 2.78e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPAN 757
Cdd:cd11982      3 FMAVKPYQSQAEGEISLSKGEKIKV--LSVGEGGFWEGQVKGRVGWFPSD 50

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212858 Cd Length: 57 Bit Score: 42.68 E-value: 2.78e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYV 1167
Cdd:cd11925      4 LALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSlrTGVSGVFPGNYV 54

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 47.60 E-value: 2.84e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  347 AQLERAEQERKE-RERQEQERKRQLELEKQLEKqrelerqreeerrkeierrEAAKRELERQrQLEWERNRRQELLNQRN 425
Cdd:COG1340      8 SSLEELEEKIEElREEIEELKEKRDELNEELKE-------------------LAEKRDELNA-QVKELREEAQELREKRD 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  426 KEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCR---LTTQRQEIE-----------STNKSREL--RIAEIth 489
Cdd:COG1340     68 ELNEKVKELKEERDELNEKLNELREELDELRKELAELNKAggsIDKLRKEIErlewrqqtevlSPEEEKELveKIKEL-- 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  490 lqqqlqesqqmlgrlipeKQILNDQLKQVQQnslHRDSLVTLKRALEAKELARQH------LRDQLDEVEKETRSKLQEI 563
Cdd:COG1340    146 ------------------EKELEKAKKALEK---NEKLKELRAELKELRKEAEEIhkkikeLAEEAQELHEEMIELYKEA 204

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  564 DIFNnqlKELREIHnKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEE 643
Cdd:COG1340    205 DELR---KEADELH-KEIVEAQEKADELHEEIIELQKELRELRKELKKLRKKQRALKREKEKEELEEKAEEIFEKLKKGE 280


                   ....*.
gi 1061899772  644 KLKREE 649
Cdd:COG1340    281 KLTTEE 286

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 42.73 E-value: 2.86e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYV 924
Cdd:cd11796      1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFrGELNGRRGIFPEGFV 51

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 42.41 E-value: 2.94e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVIL-VTKKDGD-WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11843      4 ALYDYEGQESDELSFKAGDILTkLEEEDEQgWCKGRLDGRVGLYPANYV 52

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 42.62 E-value: 2.97e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMV--DESQTGEPGWLGGELKG-KTGWFPANY 758
Cdd:cd11864      3 RAEYDFVAESEDELSFRAGDKLRLapKELQPRVRGWLLATVDGqKIGLVPANY 55

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 42.83 E-value: 3.18e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPG-----GWWEGELQARgkkrqIGWFPANYV 1091
Cdd:cd12059      8 YEASAEDELTLRRGDRVEVLSKDSAvsgdeGWWTGKINDR-----VGIFPSNYV 56

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 48.37 E-value: 3.28e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  329 EKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELE---------KQLEKQrelerqreeerrkeierREA 399
Cdd:COG4913    287 QRRLELLEAELEELRAELARLEAELERLEARLDALREELDELEAQirgnggdrlEQLERE-----------------IER 349

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  400 AKRELERQRQlewERNRRQELLNQ----RNKEQEDIVVLKAK----KKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQ 471
Cdd:COG4913    350 LERELEERER---RRARLEALLAAlglpLPASAEEFAALRAEaaalLEALEEELEALEEALAEAEAALRDLRRELRELEA 426


                   ....
gi 1061899772  472 EIES 475
Cdd:COG4913    427 EIAS 430

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 42.77 E-value: 3.42e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  874 LQAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11975      5 VSAEAVWDHVTMANRELAFKAGDVIKVLDASNKdWWWGQIDDEEGWFPASFVRL 58

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 42.34 E-value: 3.43e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTgEPGWLGGELKGKTGWFPANY 758
Cdd:cd11804      3 VAKHDFKATAEDELSFKKGSILKVLNMED-DPNWYKAELDGKEGLIPKNY 51

Src homology 3 domain of RUN and SH3 domain-containing proteins 1 and 2; RUSC1 and RUSC2, that were originally characterized in silico. They are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. RUSC1, also called NESCA (New molecule containing SH3 at the carboxy-terminus), is highly expressed in the brain and is translocated to the nuclear membrane from the cytoplasm upon stimulation with neurotrophin. It plays a role in facilitating neurotrophin-dependent neurite outgrowth. It also interacts with NEMO (or IKKgamma) and may function in NEMO-mediated activation of NF-kB. RUSC2, also called Iporin, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212744 Cd Length: 50 Bit Score: 42.43 E-value: 3.53e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNY 1166
Cdd:cd11810      2 VRALCHHVATDSGQLSFRKGDILRVIARVDDDWLLCTRGSTKGLVPLSY 50

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 42.67 E-value: 3.54e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQargKKRQIGWFPANYVKLL 1094
Cdd:cd11916      5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSR---RTKQFGTFPGNYVKLL 58

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 42.51 E-value: 3.67e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMvdESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11961      3 KALYDYDAAEDNELSFFENDKII--NIEFVDDDWWLGECHGSRGLFPSNYVE 52

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 42.31 E-value: 3.75e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMV-DESQTgepGWLGGELKGKTGWFPANY 758
Cdd:cd11963      5 RALYDFEAVEDNELTFKHGEIIIVlDDSDA---NWWKGENHRGVGLFPSNF 52

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 42.26 E-value: 3.77e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 927
Cdd:cd11919      2 PARAKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYeGEHHGRVGIFPRSYIELL 55

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 42.69 E-value: 3.90e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEKI 762
Cdd:cd11972      7 AIYDYTKDKEDELSFQEGAIIYV--IKKNDDGWYEGVMNGVTGLFPGNYVESI 57

Src Homology 3 domain of the p85alpha regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85alpha interacts with activated FGFR3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212843 Cd Length: 75 Bit Score: 42.96 E-value: 4.05e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVD-------------ESQTGEPGWLGG--ELKGKTGWFPANYAEKI 762
Cdd:cd11910      4 YRALYDYKKEREEDIDLHLGDILTVNkgsllalgfsegqEARPEEIGWLNGynETTGERGDFPGTYVEYI 73

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 42.35 E-value: 4.10e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYVK 1092
Cdd:cd11786      2 AKALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNG-----KQGFFPASYVQ 52

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 42.30 E-value: 4.19e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEKI 762
Cdd:cd11920      4 RAVYDFKAQTSKELSFKKGDTVYI--LRKIDQNWYEGEHHGRVGIFPISYVEKL 55

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 47.75 E-value: 4.26e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  341 KEQERLAQLERAEQE----RKERERQEQERKRQLELEKQLEKQRELERQREEERrkeierreaakreLERQRQLEWERNR 416
Cdd:PRK03918   152 RQILGLDDYENAYKNlgevIKEIKRRIERLEKFIKRTENIEELIKEKEKELEEV-------------LREINEISSELPE 218

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  417 RQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTnKSRELRIAEITHLQQqlqe 496
Cdd:PRK03918   219 LREELEKLEKEVKELEELKEEIEELEKELESLEGSKRKLEEKIRELEERIEELKKEIEEL-EEKVKELKELKEKAE---- 293

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  497 sqqmlgrlipEKQILNDQLKQvqqnslHRDSLVTLKRALEAKELARQHLRDQLDEVE------KETRSKLQEIDifnNQL 570
Cdd:PRK03918   294 ----------EYIKLSEFYEE------YLDELREIEKRLSRLEEEINGIEERIKELEekeerlEELKKKLKELE---KRL 354

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  571 KELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQE 618
Cdd:PRK03918   355 EELEERHELYEEAKAKKEELERLKKRLTGLTPEKLEKELEELEKAKEE 402

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212930 [Multi-domain] Cd Length: 56 Bit Score: 42.25 E-value: 4.45e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  706 VYYRALYPFESRSHDEITIQPGDIVMvDESQTGEPGWLGGEL-KGKTGWFPANYAE 760
Cdd:cd11997      2 VRVRALYDYTGQEADELSFKAGEELL-KIGEEDEQGWCKGRLlSGRIGLYPANYVE 56

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 42.31 E-value: 4.45e-05

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1061899772  890 LNFNKNDVITVL-EQQDM---WWFGEVQGQKGWFPKSYV 924
Cdd:cd11884     16 LSFHKGDVIKLLpKEGPLdpgWLFGTLDGRSGAFPKEYV 54

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 41.94 E-value: 4.46e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKL 1093
Cdd:cd11781      2 ARALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGR-----VGIFPASYVEI 53

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212934 Cd Length: 68 Bit Score: 42.72 E-value: 4.62e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1120 GMYDYTAQNDDELAFNKGQIINVLNKEDP---DWWKGEVNGQVGLFPSNYVKLTTDM 1173
Cdd:cd12001      7 ALYDNVAESPDELSFRKGDIMTVLERDTQgldGWWLCSLHGRQGIVPGNRLKILVGM 63

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 42.10 E-value: 4.71e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYV 924
Cdd:cd11833      4 ALYKFKPQENEDLEMRPGDKITLLDDSNEdWWKGKIEDRVGFFPANFV 51

Src Homology 3 domain of fungal BOI-like proteins; This subfamily includes the Saccharomyces cerevisiae proteins BOI1 and BOI2, and similar proteins. They contain an N-terminal SH3 domain, a Sterile alpha motif (SAM), and a Pleckstrin homology (PH) domain at the C-terminus. BOI1 and BOI2 interact with the SH3 domain of Bem1p, a protein involved in bud formation. They promote polarized cell growth and participates in the NoCut signaling pathway, which is involved in the control of cytokinesis. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212819 Cd Length: 55 Bit Score: 41.93 E-value: 4.77e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMV--DESQTGEpGW-LGGELK-GKTGWFPANY 758
Cdd:cd11886      1 LLIVIHDFNARSEDELTLKPGDKIELieDDEEFGD-GWyLGRNLRtGETGLFPVVF 55

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 42.01 E-value: 4.79e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANY 758
Cdd:cd11816      3 VARFDFEGEQEDELSFSEGDVITLKEYVGEE--WAKGELNGKIGIFPLNF 50

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 41.78 E-value: 4.85e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd11815      3 VVLHDFPAEHSDDLSLNSGEIVyLLEKIDTEWYRGKCKNTTGIFPANHVK 52

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212702 [Multi-domain] Cd Length: 54 Bit Score: 41.88 E-value: 4.94e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  966 IAMYTYESSEQGDLTFQQGD-VILVTKKDGDWWtgTVGDK---AGVFPSNYVR 1014
Cdd:cd11768      3 VALYDFQPIEPGDLPLEKGEeYVVLDDSNEHWW--RARDKngnEGYIPSNYVT 53

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 41.97 E-value: 5.16e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESqtGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd11824      2 YSVLYDYTAQEDDELSISKGDVVAVIEK--GEDGWWTVERNGQKGLVPGTYLEK 53

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 42.28 E-value: 5.18e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTG-WFPANYAEKI 762
Cdd:cd11970      7 KALFDYKAQREDELTFTKNAIIQNVEKQEG--GWWRGDYGGKKQlWFPSNYVEEI 59

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212836 [Multi-domain] Cd Length: 59 Bit Score: 41.97 E-value: 5.21e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQD---MWW-FGEVQGQKGWFPKSYVKLIS 928
Cdd:cd11903      4 QTLYPFSSVTEEELNFEKGETMEVIEKPEndpEWWkCKNSRGQVGLVPKNYVVVLS 59

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 41.70 E-value: 5.29e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTVGDKAGVFPSNY 1012
Cdd:cd11818      4 ALYDFTGENEDELSFKAGDIITeLESIDEEWMSGELRGKSGIFPKNF 50

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 41.92 E-value: 5.38e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQ---KGWFPKSYVKLI 927
Cdd:cd11965      1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQeWWIGHIEGQperKGVFPVSFVHIL 57

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 41.93 E-value: 5.38e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQ--DMWWFGE-VQGQKGWFPKSYV 924
Cdd:cd11763      1 KVRALYDFDSQPSGELSLRAGEVLTITRQDvgDGWLEGRnSRGEVGLFPSSYV 53

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 41.92 E-value: 5.42e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESQtGEpgWLGGELKGKTGWFPANY 758
Cdd:cd11992      2 YIALYPYSSSEPGDLTFNEGEEILVTQKD-GE--WWTGSIEDRTGIFPSNY 49

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 47.25 E-value: 5.47e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLPVTfedKKRENFERGNLELEKRRQALLEQQRKEQERLAQLE--------RAEQERKERERQEQERKRQ 369
Cdd:pfam15709  378 LELEQQRRFEEIRLR---KQRLEEERQRQEEEERKQRLQLQAAQERARQQQEEfrrklqelQRKKQQEEAERAEAEKQRQ 454

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  370 LELEKQLEKQrelerqreeerrKEIERREAAKRELERQRQ-LEWERNRRQELLNQRNKEQE 429
Cdd:pfam15709  455 KELEMQLAEE------------QKRLMEMAEEERLEYQRQkQEAEEKARLEAEERRQKEEE 503

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 47.42 E-value: 5.98e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  318 RENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKqLEKQrelerqreeerrkeierr 397
Cdd:PTZ00266   432 KDHAERARIEKENAHRKALEMKILEKKRIERLEREERERLERERMERIERERLERER-LERE------------------ 492

                           90       100
                   ....*....|....*....|....*..
gi 1061899772  398 EAAKRELERQRQLEWERNRRQELLNQR 424
Cdd:PTZ00266   493 RLERDRLERDRLDRLERERVDRLERDR 519

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 41.80 E-value: 6.14e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGGELK-GKTGWFPANY 758
Cdd:cd11845      2 YVALYDYEARTDDDLSFKKGDRLQILDDSDGD-WWLARHLStGKEGYIPSNY 52

First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the first C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212845 [Multi-domain] Cd Length: 55 Bit Score: 41.83 E-value: 6.20e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWW----KGevNGQVGLFPSNYVKL 1169
Cdd:cd11912      5 LYDYTASGDDEVSISEGEEVTVLEPDDGSGWtkvrNG--SGEEGLVPTSYIEI 55

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 41.80 E-value: 6.28e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNpGGWWEGELQarGKKRQIGWFPANYVKL 1093
Cdd:cd11872      4 AIYNFQGDGEHQLSLQVGDTVQILEEC-EGWYRGFSL--RNKSLKGIFPKSYVHI 55

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 41.56 E-value: 6.39e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWegELQARGKKrqiGWFPANYVK 1092
Cdd:cd12076      5 VIYPYTARDQDEINLEKGAVVEVIQKNLEGWW--KIRYQGKE---GWAPASYLK 53

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 46.82 E-value: 6.50e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  319 ENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLElekqlEKQRELERQREEERRKEIERRE 398
Cdd:COG4372     31 EQLRKALFELDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELE-----ELNEQLQAAQAELAQAQEELES 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  399 AAKRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQdircRLTTQRQEIESTNK 478
Cdd:COG4372    106 LQEEAEELQEELEELQKERQDLEQQRKQLEAQIAELQSEIAEREEELKELEEQLESLQEELA----ALEQELQALSEAEA 181

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  479 SREL-RIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETR 557
Cdd:COG4372    182 EQALdELLKEANRNAEKEEELAEAEKLIESLPRELAEELLEAKDSLEAKLGLALSALLDALELEEDKEELLEEVILKEIE 261

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  558 SKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDE 632
Cdd:COG4372    262 ELELAILVEKDTEEEELEIAALELEALEEAALELKLLALLLNLAALSLIGALEDALLAALLELAKKLELALAILL 336

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 41.90 E-value: 6.58e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  962 GEEFIAMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKA--GVFPSNYVR 1014
Cdd:cd11917      4 GEPFQALYNYMPRNEDELELREGDVIDVMEKcDDGWFVGTSRRTKffGTFPGNYVK 59

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212703 [Multi-domain] Cd Length: 57 Bit Score: 41.52 E-value: 6.61e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  962 GEEFIAMYTYESSEQGDLTFQQGDVILVTK--KDGDWWTG-TVGDKAGVFPSNYV 1013
Cdd:cd11769      1 GTECIAKYNFNGASEEDLPFKKGDILTIVAvtKDPNWYKAkNKDGREGMIPANYV 55

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 41.56 E-value: 6.74e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11781      3 RALYPFKAQSAKELSLKKGDIIYIRRQiDKNWYEGEHNGRVGIFPASYV 51

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 45.69 E-value: 6.75e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  327 ELEKRRQALLEQQRKEQERLAQLERA-EQERKERERQEQERKrqlELEKQLEKqrelerqreeerrkeierreaAKRELE 405
Cdd:COG1579     14 ELDSELDRLEHRLKELPAELAELEDElAALEARLEAAKTELE---DLEKEIKR---------------------LELEIE 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  406 RQRQLEwERNRRQELLNQRNKE----QEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRE 481
Cdd:COG1579     70 EVEARI-KKYEEQLGNVRNNKEyealQKEIESLKRRISDLEDEILELMERIEELEEELAELEAELAELEAELEEKKAELD 148


                   ....*.
gi 1061899772  482 LRIAEI 487
Cdd:COG1579    149 EELAEL 154

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 41.87 E-value: 6.78e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVG--DKAGVFPSNYVRL 1015
Cdd:cd11924      2 EAVAQYTFKGDLEVELSFRKGEHIcLIRKVNENWYEGRITgtGRQGIFPASYVQV 56

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 41.52 E-value: 6.87e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF---GEVQGQKGWFPKSYVK 925
Cdd:cd11780      3 RALYSYTPQNEDELELREGDIVYVMEKCDDGWFvgtSERTGLFGTFPGNYVA 54

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 47.27 E-value: 6.93e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  294 EEPVLEDEQQQLEKKLPVTFE----DKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQ 369
Cdd:pfam02463  417 LEDLLKEEKKEELEILEEEEEsielKQGKLTEEKEELEKQELKLLKDELELKKSEDLLKETQLVKLQEQLELLLSRQKLE 496

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  370 LELEKQLEKQRELERQREEERRKEIERREAAKRELERQ--------------RQLEWERNRRQELLNQRNKEQEDIVVLK 435
Cdd:pfam02463  497 ERSQKESKARSGLKVLLALIKDGVGGRIISAHGRLGDLgvavenykvaistaVIVEVSATADEVEERQKLVRALTELPLG 576

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  436 AKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQL 515
Cdd:pfam02463  577 ARKLRLLIPKLKLPLKSIAVLEIDPILNLAQLDKATLEADEDDKRAKVVEGILKDTELTKLKESAKAKESGLRKGVSLEE 656

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  516 KQVQQNSLHRDSLVTLKRALEAKELarqhLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLK- 594
Cdd:pfam02463  657 GLAEKSEVKASLSELTKELLEIQEL----QEKAESELAKEEILRRQLEIKKKEQREKEELKKLKLEAEELLADRVQEAQd 732

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  595 -----QKEQERKIIElEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREES 650
Cdd:pfam02463  733 kineeLKLLKQKIDE-EEEEEEKSRLKKEEKEEEKSELSLKEKELAEEREKTEKLKVEEEK 792

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 47.34 E-value: 6.97e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  289 DQRLPEEPVLEDEQQQLEkklpvtfeDKKRENFERGNLELEKRRQALlEQQRKEQErlAQLERAEQERkereRQEQERKR 368
Cdd:PRK02224   173 DARLGVERVLSDQRGSLD--------QLKAQIEEKEEKDLHERLNGL-ESELAELD--EEIERYEEQR----EQARETRD 237

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  369 QLE--LEKQLEKQrelerQREEERRKEIERREAAKRELERQR-----QLEWERNRRQELLNQRNKEQEDIVVLKAKKKTL 441
Cdd:PRK02224   238 EADevLEEHEERR-----EELETLEAEIEDLRETIAETEREReelaeEVRDLRERLEELEEERDDLLAEAGLDDADAEAV 312

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  442 EFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKS---RELRIAEITHLQQQLQESQQMLGRLIPEKQ----ILNDQ 514
Cdd:PRK02224   313 EARREELEDRDEELRDRLEECRVAAQAHNEEAESLREDaddLEERAEELREEAAELESELEEAREAVEDRReeieELEEE 392

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  515 LKQVQQNslHRDSLVTLKRALEAKELARQHlRDQLDEVEKETRSKLQEIDIFNNQLKELREIHN----KQQL-------- 582
Cdd:PRK02224   393 IEELRER--FGDAPVDLGNAEDFLEELREE-RDELREREAELEATLRTARERVEEAEALLEAGKcpecGQPVegsphvet 469

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  583 -----QKQKSMEAERLKQKEQ----ERKIIELEKQKEEAQRRaqERDKQWLEHVQQEDEHQRPRKlhEEEKLKREE 649
Cdd:PRK02224   470 ieedrERVEELEAELEDLEEEveevEERLERAEDLVEAEDRI--ERLEERREDLEELIAERRETI--EEKRERAEE 541

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212997 Cd Length: 56 Bit Score: 41.64 E-value: 7.00e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGdIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd12064      4 KALYACKAEHDSELSFTAG-TVFDNVHPSQEPGWLEGTLNGKTGLIPENYVE 54

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 47.34 E-value: 7.03e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  313 FEDKKRENFERGNLELEKRRQALleQQRKEQERLAQ---LERAEQERKE----RERQEQERKRQLELEKQLEKQRELERQ 385
Cdd:PRK02224   304 LDDADAEAVEARREELEDRDEEL--RDRLEECRVAAqahNEEAESLREDaddlEERAEELREEAAELESELEEAREAVED 381

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  386 REEERRKEIERREAAKRELE-RQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEfelEALNDKKHQLE-GKL---- 459
Cdd:PRK02224   382 RREEIEELEEEIEELRERFGdAPVDLGNAEDFLEELREERDELREREAELEATLRTAR---ERVEEAEALLEaGKCpecg 458

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  460 QDIR----------CR-----LTTQRQEIESTNKSRELRIAEITHLQQQlqesqqmlgrlipEKQIlnDQLKQVQQNSlh 524
Cdd:PRK02224   459 QPVEgsphvetieeDRerveeLEAELEDLEEEVEEVEERLERAEDLVEA-------------EDRI--ERLEERREDL-- 521

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  525 rDSLVTLKRA-LEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREihNKQQLQKQKSMEAERLKQKEQERKII 603
Cdd:PRK02224   522 -EELIAERREtIEEKRERAEELRERAAELEAEAEEKREAAAEAEEEAEEARE--EVAELNSKLAELKERIESLERIRTLL 598

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772  604 ELEKQKEEAQRRAQERDKQWlehvqQEDEHQRPRKLHEEEKLKRE 648
Cdd:PRK02224   599 AAIADAEDEIERLREKREAL-----AELNDERRERLAEKRERKRE 638

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212789 [Multi-domain] Cd Length: 55 Bit Score: 41.64 E-value: 7.55e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  967 AMYTYESSEQ--GDLTFQQGDVILVTKKDGDWWTGTVGD-KAGVFPSNYVRL 1015
Cdd:cd11855      4 ALYPYDASPDdpNELSFEKGEILEVSDTSGKWWQARKSNgETGICPSNYLQL 55

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 41.60 E-value: 7.59e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQV--GLFPSNYVKL 1169
Cdd:cd11858      5 LYDFAGSVANELSLKKDDIVYIVQKEDNGWWLAKKLDESkeGWVPAAYLEE 55

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 41.54 E-value: 7.94e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLI-LIRKKNPGGWWEGELQaRGKKRqiGWFPANYVK 1092
Cdd:cd11779      4 KALYPHAAGGETQLSFEEGDVItLLGPEPRDGWHYGENE-RSGRR--GWFPIAYTE 56

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 41.33 E-value: 8.03e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKD-GDWWT-GTVGDKAGVFPSNY 1012
Cdd:cd11778      4 ALYDYEAQGDDEISIRVGDRIAVIRGDdGSGWTyGEINGVKGLFPTSY 51

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212698 [Multi-domain] Cd Length: 54 Bit Score: 41.48 E-value: 8.14e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDpDWWKGE-VNGQVGLFPSN 1165
Cdd:cd11764      5 LYDFTARNSKELSVLKGEYLEVLDDSR-QWWKVRnSRGQVGYVPHN 49

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 41.56 E-value: 8.16e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQ----DMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11844      2 ARALYDNVAESPDELAFRRGDILTVLEQNtaglEGWWLCSLRGRQGIAPGNRLKL 56

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 41.53 E-value: 8.45e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  968 MYTYESSEQGDLTFQQGDVILVT-KKDGDWWTGTV---GDKAGVFPSNYVRL 1015
Cdd:cd11965      5 IYDCQADNDDELTFVEGEVIIVTgEEDQEWWIGHIegqPERKGVFPVSFVHI 56

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 41.17 E-value: 8.58e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11874      1 RCKVLFSYTPQNEDELELKVGDTIEVLGEvEEGWWEGKLNGKVGVFPSNFVKE 53

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 41.51 E-value: 8.64e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELqarGKKRQIgWFPANYVK 1092
Cdd:cd11970     12 YKAQREDELTFTKNAIIQNVEKQEGGWWRGDY---GGKKQL-WFPSNYVE 57

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 41.36 E-value: 8.75e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIV-MVDESqtgEPGWLGGELKGKTGWFPANY 758
Cdd:cd11949      1 YVQALFDFDPQEDGELGFRRGDFIeVMDNS---DPNWWKGACHGQTGMFPRNY 50

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 41.33 E-value: 8.89e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1038 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGelQARGKkrqIGWFPANYVK 1092
Cdd:cd12046      1 QVVAlfSYEASQPEDLEFQKGDVILVLSKVNEDWLEG--QCKGK---IGIFPSAFVE 52

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 41.14 E-value: 9.00e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPG--GWWEGELqargkKRQIGWFPANYVK 1092
Cdd:cd11987      8 FEARSHDEITIQPGDIVMVDESQTGepGWLGGEL-----KGKTGWFPANYAE 54

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212935 Cd Length: 57 Bit Score: 41.51 E-value: 9.29e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKED---PDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd12002      5 LYDNVPECAEELAFRKGDILTVIEQNTgglEGWWLCSLHGRQGIAPGNRLKL 56

Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212856 [Multi-domain] Cd Length: 57 Bit Score: 41.44 E-value: 9.36e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNG--QVGLFPSNYVKL 1169
Cdd:cd11923      2 EAVAKYNFNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPGtnRQGIFPVSYVEV 56

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 41.53 E-value: 9.92e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLISGP 930
Cdd:cd11972      7 AIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYeGVMNGVTGLFPGNYVESIMHY 60

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 41.17 E-value: 1.02e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772  969 YTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11901      8 FNYTAEREDELSLVKGTKVIVMEKCSDgWWRGSYNGQVGWFPSNYV 53

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 46.71 E-value: 1.03e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEK---KLPVTFEDKKrENFERgnlELEKRRQALLEQQRKEQERLAQLE-RAEQERKERErQEQERKRQLELE 373
Cdd:pfam01576  704 LEDELQATEDaklRLEVNMQALK-AQFER---DLQARDEQGEEKRRQLVKQVRELEaELEDERKQRA-QAVAAKKKLELD 778

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  374 -KQLEKQRELERQREEERRKEIERREAAKRELerQRQLEWERNRRQELLNQ-RNKE-------------QEDIVVLKAKK 438
Cdd:pfam01576  779 lKELEAQIDAANKGREEAVKQLKKLQAQMKDL--QRELEEARASRDEILAQsKESEkklknleaellqlQEDLAASERAR 856

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  439 KTLEFELEALNDK-KHQLEGK--LQDIRCRLTTQRQEIESTNKSRELRIaeithlqqqlqesqqmlgrlipekQILNDQL 515
Cdd:pfam01576  857 RQAQQERDELADEiASGASGKsaLQDEKRRLEARIAQLEEELEEEQSNT------------------------ELLNDRL 912

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  516 -KQVQQNSLHRDSLVTLKRALEAKELARQHLRDQldevEKETRSKLQEID--IFNNQLKELREIHNK-QQLQKQKSMEAE 591
Cdd:pfam01576  913 rKSTLQVEQLTTELAAERSTSQKSESARQQLERQ----NKELKAKLQEMEgtVKSKFKSSIAALEAKiAQLEEQLEQESR 988

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  592 RLKQ-----KEQERKIIELEKQKEEAQRRAQE----------RDKQwLEHVQQEDEHQRPRKLHEEEKLKRE 648
Cdd:pfam01576  989 ERQAanklvRRTEKKLKEVLLQVEDERRHADQykdqaekgnsRMKQ-LKRQLEEAEEEASRANAARRKLQRE 1059

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1)-like proteins; This subfamily includes MPP1, CASK (Calcium/calmodulin-dependent Serine protein Kinase), Caenorhabditis elegans lin-2, and similar proteins. MPP1 and CASK are scaffolding proteins from the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). In addition, they also have the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. CASK and lin-2 also contain an N-terminal calmodulin-dependent kinase (CaMK)-like domain and two L27 domains. MPP1 is ubiquitously-expressed and plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. CASK is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212968 Cd Length: 62 Bit Score: 41.26 E-value: 1.04e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1118 VIGMYDYTAQNDD-------ELAFNKGQIINVLNKEDPDWWKGEV----NGQVGLFPS 1164
Cdd:cd12035      2 VRAQFDYDPSKDDlipcqqaGIAFKTGDILQIISKDDHNWWQARKpgasKEPAGLIPS 59

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

Pssm-ID: 405931 [Multi-domain] Cd Length: 151 Bit Score: 43.89 E-value: 1.04e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  288 VDQRLPEEpvLEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQALL-EQQRKEQERLAQLERAEQERKERERQEQER 366
Cdd:pfam15346   20 VAKRVEEE--LEKRKDEIEAEVERRVEEARKIMEKQVLEELEREREAELeEERRKEEEERKKREELERILEENNRKIEEA 97

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  367 KRQLELEKQlekqrelerqreeerrkeierreaakRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKAK 437
Cdd:pfam15346   98 QRKEAEERL--------------------------AMLEEQRRMKEERQRREKEEEEREKREQQKILNKKN 142

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 46.60 E-value: 1.08e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  316 KKRENFERGNLELEKRRQALLEQQRKEQERLAQLERA-EQERKERERQEQERKRQLELEKQLEKqRELERQREEERRKei 394
Cdd:PRK03918   186 KRTENIEELIKEKEKELEEVLREINEISSELPELREElEKLEKEVKELEELKEEIEELEKELES-LEGSKRKLEEKIR-- 262

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  395 erreaakrELERQRQlewERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQdircRLTTQRQEIE 474
Cdd:PRK03918   263 --------ELEERIE---ELKKEIEELEEKVKELKELKEKAEEYIKLSEFYEEYLDELREIEKRLS----RLEEEINGIE 327

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  475 STNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQL-KQVQQNSLHRD----SLVTLKRALEAKELARQHLRDQL 549
Cdd:PRK03918   328 ERIKELEEKEERLEELKKKLKELEKRLEELEERHELYEEAKaKKEELERLKKRltglTPEKLEKELEELEKAKEEIEEEI 407

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  550 DEVEKETRSKLQEIDIFNNQLKELREIHNKQQL--------QKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDK 621
Cdd:PRK03918   408 SKITARIGELKKEIKELKKAIEELKKAKGKCPVcgrelteeHRKELLEEYTAELKRIEKELKEIEEKERKLRKELRELEK 487

                          330       340       350
                   ....*....|....*....|....*....|
gi 1061899772  622 QwlehVQQEDEHQRPRKLHE-----EEKLK 646
Cdd:PRK03918   488 V----LKKESELIKLKELAEqlkelEEKLK 513

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 41.03 E-value: 1.10e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTG-TVGDKA--GVFPSNYVRLK 1016
Cdd:cd11872      3 VAIYNFQGDGEHQLSLQVGDTVQILEECEGWYRGfSLRNKSlkGIFPKSYVHIK 56

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 41.13 E-value: 1.10e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1042 SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYV 1091
Cdd:cd11772      7 DYEAQHPDELSFEEGDLLYISDKSDPNWWKATC--GGKT---GLIPSNYV 51

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 41.13 E-value: 1.12e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF---GEVQGQKGWFPKSYVKLI 927
Cdd:cd11916      5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFvgtSRRTKQFGTFPGNYVKLL 58

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 41.23 E-value: 1.13e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMV--DESQTGEPGWLGGELKGKTGWFPA 756
Cdd:cd11762      1 LVRALYDYEAQSDEELSFPEGAIIRIlrKDDNGVDDGWWEGEFNGRVGVFPS 52

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 41.17 E-value: 1.13e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772 1124 YTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd12077      9 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 53

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 40.96 E-value: 1.13e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1035 EIAQVIASYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQarGKKrqiGWFPANYVKL 1093
Cdd:cd12056      2 EYCKALFHYEGTNEDELDFKEGEIILIISKDTGepGWWKGELN--GKE---GVFPDNFVSQ 57

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 40.96 E-value: 1.15e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTG---TVGdKAGVFPSNYV 1013
Cdd:cd12005      3 VALYSYEPSHDGDLGFEKGEKLRILEQSGEWWKAqslTTG-QEGFIPFNFV 52

Src Homology 3 domain of Cdc42-Interacting Protein 4, Bzz1 and similar domains; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4) and similar proteins such as Formin Binding Protein 17 (FBP17) and FormiN Binding Protein 1-Like (FNBP1L), as well as yeast Bzz1 (or Bzz1p). CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. Bzz1 is also a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Members of this subfamily contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain as well as at least one C-terminal SH3 domain. Bzz1 contains a second SH3 domain at the C-terminus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212711 [Multi-domain] Cd Length: 55 Bit Score: 41.05 E-value: 1.15e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGGELK-GKTGWFPANYA 759
Cdd:cd11777      3 KALYAFVGSSEGTISMTEGEKLSLVEEDKGD-GWTRVRRDtGEEGYVPTSYI 53

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 40.92 E-value: 1.18e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKkrqIGWFPANYV 1091
Cdd:cd11784      4 ALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLSLVTGR---VGIFPSNYV 53

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 46.31 E-value: 1.18e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  326 LELEKRRQALLEQQRKEQE---RLAQLERAEQERKERERQEQE-RKRQLELEKQLekqrelerqreeerrkeierreaaK 401
Cdd:PRK12704    34 KEAEEEAKRILEEAKKEAEaikKEALLEAKEEIHKLRNEFEKElRERRNELQKLE------------------------K 89

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  402 RELERQRQLEwernRRQELLNQRNKEqedivvLKAKKKTLEFELEALNDKKHQLEGKLQDircrlttQRQEIES 475
Cdd:PRK12704    90 RLLQKEENLD----RKLELLEKREEE------LEKKEKELEQKQQELEKKEEELEELIEE-------QLQELER 146

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 40.84 E-value: 1.19e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11806      4 AIADFVATDDSQLSFESGDKLLVLRKpSVDWWWAEHNGCCGYIPASHL 51

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

Pssm-ID: 293879 [Multi-domain] Cd Length: 291 Bit Score: 45.26 E-value: 1.21e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  294 EEPVLEDEQQQLEKKLpvtfEDKKReNFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELE 373
Cdd:cd16269    213 ERKLLEEQQRELEQKL----EDQER-SYEEHLRQLKEKMEEERENLLKEQERALESKLKEQEALLEEGFKEQAELLQEEI 287


                   ....
gi 1061899772  374 KQLE 377
Cdd:cd16269    288 RSLK 291

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 41.03 E-value: 1.22e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772  712 YPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANY 758
Cdd:cd12052      6 FDYKAQHEDELTITVGDIITKIKKDDG--GWWEGEIKGRRGLFPDNF 50

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 40.81 E-value: 1.23e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1038 QVIASY--TATGPEQLTLAPGQLILIRKKNPGgWWEGELQargkKRQIGWFPANYVKL 1093
Cdd:cd11837      1 TATALYpwRAKKENHLSFAKGDIITVLEQQEM-WWFGELE----GGEEGWFPKSYVKE 53

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 40.83 E-value: 1.28e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESQTGepGW-LGGELKG-KTGWFPANYAE 760
Cdd:cd11858      2 YKALYDFAGSVANELSLKKDDIVYIVQKEDN--GWwLAKKLDEsKEGWVPAAYLE 54

Second Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212865 Cd Length: 57 Bit Score: 40.98 E-value: 1.30e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1115 VCQVIGMYDY----TAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11932      1 LCRALYNFDLkeknREESKDCLKFQKDDIITVISRVDENWAEGKLGDQVGIFPILFV 57

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 40.95 E-value: 1.30e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDeSQTGEPGWLGgELKGKTGWFPANYAE 760
Cdd:cd11813      3 KALLDFERHDDDELGFRKNDIITII-SQKDEHCWVG-ELNGLRGWFPAKFVE 52

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212872 [Multi-domain] Cd Length: 55 Bit Score: 40.70 E-value: 1.33e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEV--QGQKGWFPKSYVK 925
Cdd:cd11939      1 QVQCVHPYVSQEPDELSLELADVLNILDKtDDGWIFGERlhDQERGWFPSSVVE 54

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 40.55 E-value: 1.43e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGElqarGKKRQIGWFPANYVKL 1093
Cdd:cd11962      2 AVVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGT----NSKGESGLFPSNYVEL 54

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 46.06 E-value: 1.43e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLpvTFEDKKRENFERGNLELEKRRQALLEQQRKEQ-ERLAQLERaEQERKERERQEQERKRQlELEKQL 376
Cdd:COG4913    293 LEAELEELRAEL--ARLEAELERLEARLDALREELDELEAQIRGNGgDRLEQLER-EIERLERELEERERRRA-RLEALL 368

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  377 EKQRELERQREEERRKEIERREAAKRELERQRqlEWERNRRQELLNQRNKeqedivvLKAKKKTLEFELEALNDKKHQLE 456
Cdd:COG4913    369 AALGLPLPASAEEFAALRAEAAALLEALEEEL--EALEEALAEAEAALRD-------LRRELRELEAEIASLERRKSNIP 439

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  457 GKLQDIRCRLTTQ-----------------RQE--------------------------------IESTNKSRELRIAEI 487
Cdd:COG4913    440 ARLLALRDALAEAlgldeaelpfvgelievRPEeerwrgaiervlggfaltllvppehyaaalrwVNRLHLRGRLVYERV 519

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  488 THLQQQLQESQQMLGRLIPE------------KQILN-----------DQLK----------QVQQN-SLH--------- 524
Cdd:COG4913    520 RTGLPDPERPRLDPDSLAGKldfkphpfrawlEAELGrrfdyvcvdspEELRrhpraitragQVKGNgTRHekddrrrir 599

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  525 ---------RDSLVTLKRALEAKELARQHLRDQLDEVEKET------RSKLQEIDIFNNQLKELREIHNK-QQLQKQK-- 586
Cdd:COG4913    600 sryvlgfdnRAKLAALEAELAELEEELAEAEERLEALEAELdalqerREALQRLAEYSWDEIDVASAEREiAELEAELer 679

                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  587 ----SMEAERLKQ--KEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQR 635
Cdd:COG4913    680 ldasSDDLAALEEqlEELEAELEELEEELDELKGEIGRLEKELEQAEEELDELQD 734

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 45.57 E-value: 1.46e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  578 NKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREESVKKKDGE 657
Cdd:PRK09510    65 NRQQQQQKSAKRAEEQRKKKEQQQAEELQQKQAAEQERLKQLEKERLAAQEQKKQAEEAAKQAALKQKQAEEAAAKAAAA 144

                           90
                   ....*....|
gi 1061899772  658 EKGKQEAQDK 667
Cdd:PRK09510   145 AKAKAEAEAK 154

Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. It has been shown to interact with CSF1R, c-Cbl, LAT, CD247, and Zap70. SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212944 Cd Length: 55 Bit Score: 40.50 E-value: 1.46e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKKDGDWWT--GTVGDKAGVFPSNYV 1013
Cdd:cd12011      2 AVALCNFPSGGPTELSIRMGEQLTILSEDGDWWKvsSAVTGRECYIPSNYV 52

First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212811 [Multi-domain] Cd Length: 54 Bit Score: 40.73 E-value: 1.56e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPD-WWKGE--VNGQVGLFPSNY 1166
Cdd:cd11878      6 YDYRAQTPGELSFSKGDFFHVIGEEDQGeWYEATnpVTGKRGLVPKSY 53

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 40.65 E-value: 1.56e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772  880 YPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 925
Cdd:cd12052      6 FDYKAQHEDELTITVGDIITKIKKDDGgWWEGEIKGRRGLFPDNFVR 52

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 40.76 E-value: 1.58e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVIL-VTKKDGDWWTGTV--GDKAGVFPSNYVRL 1015
Cdd:cd11935      5 AMYDYSAQDEDEVSFRDGDYIVnVQPIDEGWMYGTVqrTGRTGMLPANYIEF 56

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212830 [Multi-domain] Cd Length: 55 Bit Score: 40.74 E-value: 1.62e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVN--GQVGLFPSNYVKL 1169
Cdd:cd11897      5 LYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNsrGDRGLFPASYVEV 55

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 40.78 E-value: 1.64e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDV--ILVTKKDGDWWTGTVGDKAGVFPSNYVRLK 1016
Cdd:cd11946      2 EAIAKYDFKATADDELSFKRGDIlkVLNEECDQNWYKAELNGKDGFIPKNYIEMK 56

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 40.57 E-value: 1.64e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELqarGKKRQiGWFPANYV 1091
Cdd:cd11812      8 YTANRSDELTIHRGDIIRVLYKDNDNWWFGSL---VNGQQ-GYFPANYV 52

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 40.64 E-value: 1.66e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM----WWFGEVQGQKGWFPKSYVKLI 927
Cdd:cd12003      3 AKALYDNAAESPEELSFRRGDVLMVLKREHGslpgWWLCSLHGQQGIAPANRLRLL 58

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212954 [Multi-domain] Cd Length: 53 Bit Score: 40.32 E-value: 1.67e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYVK 1092
Cdd:cd12021      3 RAIADYEKSSKSEMALKTGDVVEVVEKSENGWWFCQLKAKR-----GWVPASYLE 52

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 40.55 E-value: 1.68e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGelqARGKKRQIGWFPANYVKL 1093
Cdd:cd11940      3 QCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEG---VRLSDGERGWFPQSHVEE 55

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 40.43 E-value: 1.69e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANY 758
Cdd:cd11837      2 ATALYPWRAKKENHLSFAKGDIITVLEQQ--EMWWFGELEGGEEGWFPKSY 50

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 40.68 E-value: 1.70e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVM----VDESqtgepgWLGGELKGKTGWFPANYAE 760
Cdd:cd11928      2 CGKALYSYEGKEPGDLKFNKGDIIIlrrkVDEN------WYHGELNGCHGFLPASYIQ 53

chromosome partition protein MukB;

Pssm-ID: 235316 [Multi-domain] Cd Length: 1486 Bit Score: 46.10 E-value: 1.75e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  314 EDKKRENFERGnLELEKRRQALLEQQRKEQERLAQLERAEQERKERER----------------------QEQERKRQ-- 369
Cdd:PRK04863   278 ANERRVHLEEA-LELRRELYTSRRQLAAEQYRLVEMARELAELNEAESdleqdyqaasdhlnlvqtalrqQEKIERYQad 356

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  370 -LELEKQLEKQRELERQREEERRKEIERREAAKRELER-QRQLEwERNRRQELLNQRNKEQEDIVVLKAKKKTL----EF 443
Cdd:PRK04863   357 lEELEERLEEQNEVVEEADEQQEENEARAEAAEEEVDElKSQLA-DYQQALDVQQTRAIQYQQAVQALERAKQLcglpDL 435

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  444 ELEALNDKKHQLEGKLQDircrLTTQRQEIEstnksRELRIAEITHLQQQLQEsqqmlgrlipekQILNDQLKQVQQNSL 523
Cdd:PRK04863   436 TADNAEDWLEEFQAKEQE----ATEELLSLE-----QKLSVAQAAHSQFEQAY------------QLVRKIAGEVSRSEA 494

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  524 HRDSLVTLKRALEAKELA--RQHLRDQLDEVEKETRSKlqeidifNNQLKELREIHNKQQLQKQKSMEAERLkQKEQERK 601
Cdd:PRK04863   495 WDVARELLRRLREQRHLAeqLQQLRMRLSELEQRLRQQ-------QRAERLLAEFCKRLGKNLDDEDELEQL-QEELEAR 566

                          330       340
                   ....*....|....*....|..
gi 1061899772  602 IIELEKQKEEA-QRRAQERDKQ 622
Cdd:PRK04863   567 LESLSESVSEArERRMALRQQL 588

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53; IRSp53 is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 can also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRSp53 has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212848 Cd Length: 59 Bit Score: 40.77 E-value: 1.80e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772  875 QAQALYPwRAKKDNH--LNFNKNDVITVL--EQQDMWWFGEVQGQK--GWFPKSYVKLI 927
Cdd:cd11915      2 RVQAIFS-HAAGDNStlLSFKEGDYITLLvpEARDGWHYGECEKTKmrGWFPFSYTRVL 59

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 40.39 E-value: 1.80e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPG-GWWEGElQARGKkrqIGWFPANYV 1091
Cdd:cd11763      2 VRALYDFDSQPSGELSLRAGEVLTITRQDVGdGWLEGR-NSRGE---VGLFPSSYV 53

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 45.87 E-value: 1.84e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEK-KLPVTFEDKKRENFERGNLEL-EKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERK-------- 367
Cdd:pfam05483   83 LYKEAEKIKKwKVSIEAELKQKENKLQENRKIiEAQRKAIQELQFENEKVSLKLEEEIQENKDLIKENNATRhlcnllke 162

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  368 ---RQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQ---------LEWERNRRQELLNQRNKE---QEDIV 432
Cdd:pfam05483  163 tcaRSAEKTKKYEYEREETRQVYMDLNNNIEKMILAFEELRVQAEnarlemhfkLKEDHEKIQHLEEEYKKEindKEKQV 242

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  433 VL--------KAKKKTLEFELEALNDKKHQLE--GKLQDIRCRLTTQRQ-----EIESTNKSRELRIAEITHLQQQLQES 497
Cdd:pfam05483  243 SLlliqitekENKMKDLTFLLEESRDKANQLEekTKLQDENLKELIEKKdhltkELEDIKMSLQRSMSTQKALEEDLQIA 322

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  498 QQMLGRLIPEKQILNDQLKQVQQN-----SLHRDSLVTLKRALEAKELARQHLRDQLD----EVEKETrSKLQEIDIFNN 568
Cdd:pfam05483  323 TKTICQLTEEKEAQMEELNKAKAAhsfvvTEFEATTCSLEELLRTEQQRLEKNEDQLKiitmELQKKS-SELEEMTKFKN 401

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  569 ----QLKELREIHNKQQ--LQKQKSME--AERLKQKEQERKIIELEKQKE----EAQRRAQERDKQwleHVQQEDEHQRP 636
Cdd:pfam05483  402 nkevELEELKKILAEDEklLDEKKQFEkiAEELKGKEQELIFLLQAREKEihdlEIQLTAIKTSEE---HYLKEVEDLKT 478

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772  637 RKlhEEEKLKREE----SVKKKDGEEKGKQEAQDKLGRLfHQHQE 677
Cdd:pfam05483  479 EL--EKEKLKNIEltahCDKLLLENKELTQEASDMTLEL-KKHQE 520

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 40.37 E-value: 1.90e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLE-QQDMWWFGE-VQGQKGWFPKSYVKL 926
Cdd:cd11770      4 ALSDFQAEQEGDLSFKKGEVLRIISkRADGWWLAEnSKGNRGLVPKTYLKV 54

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212695 [Multi-domain] Cd Length: 57 Bit Score: 40.42 E-value: 1.96e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGG-ELKGKTGWFPANYAEK 761
Cdd:cd11761      6 VLYSYEAQRPDELTITEGEELEVIEDGDGD-GWVKArNKSGEVGYVPENYLQF 57

First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the first C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212845 [Multi-domain] Cd Length: 55 Bit Score: 40.28 E-value: 2.02e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGEpGW----LGGelkGKTGWFPANYAE 760
Cdd:cd11912      3 KVLYDYTASGDDEVSISEGEEVTVLEPDDGS-GWtkvrNGS---GEEGLVPTSYIE 54

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212935 Cd Length: 57 Bit Score: 40.35 E-value: 2.04e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQ----DMWWFGEVQGQKGWFPKSYVKLI 927
Cdd:cd12002      2 ARALYDNVPECAEELAFRKGDILTVIEQNtgglEGWWLCSLHGRQGIAPGNRLKLL 57

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 40.40 E-value: 2.10e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772  881 PWRAKKDNHLNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd12077      8 PYTSQGKDEIGFEKGVTVEVIQKNlEGWWYIRYLGKEGWAPASYLK 53

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212828 Cd Length: 58 Bit Score: 40.33 E-value: 2.12e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-----DGDWWTGTVGDKAGVFPS 1010
Cdd:cd11895      4 ALYSYTGQSPEELSFPEGALIRLLPRaqdgvDDGFWRGEFGGRVGVFPS 52

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212859 [Multi-domain] Cd Length: 55 Bit Score: 40.34 E-value: 2.14e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTV--GDKAGVFPSNYV 1013
Cdd:cd11926      2 YVAIYPYTPRKEDELELRKGEMFLVFERCQDgWFKGTSmhTSKIGVFPGNYV 53

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 40.34 E-value: 2.18e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMV---DESqtgepGWLGGEL-----KGKTGWFPANY 758
Cdd:cd11883      3 VALYDFTPKSKNQLSFKAGDIIYVlnkDPS-----GWWDGVIisssgKVKRGWFPSNY 55

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 40.38 E-value: 2.21e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11920      5 AVYDFKAQTSKELSFKKGDTVYILRKiDQNWYEGEHHGRVGIFPISYV 52

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212890 Cd Length: 52 Bit Score: 40.28 E-value: 2.21e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILV-TKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11957      1 EVKALCHHIATEPGQLSFNKGDILQVlSRADGDWLRCSLGPDSGLVPIAYV 51

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212869 Cd Length: 62 Bit Score: 40.41 E-value: 2.21e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVM---VDESQTGEpGWLGGE--LKGKTGWFPANYAEK 761
Cdd:cd11936      5 QVIYPYTPQNDDELELVPGDYIFmspMEQTSTSE-GWIYGTslTTGCSGLLPENYITK 61

Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212736 [Multi-domain] Cd Length: 52 Bit Score: 39.96 E-value: 2.24e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINV--LNKEDPDWWKGEVNGQVGLFPSNY 1166
Cdd:cd11802      5 LYDYDAEDSTELSLLADEVITVyeLPGMDEDYMMGERGSQRGKVPVAY 52

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 40.36 E-value: 2.31e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTV--GDKAGVFPSNYVRL 1015
Cdd:cd11916      6 ALYSYAPQNDDELELRDGDIVDVMEKcDDGWFVGTSrrTKQFGTFPGNYVKL 57

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 40.30 E-value: 2.32e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQG-----QKGWFPKSYVKLI 927
Cdd:cd11994      2 AQVTTAYVASGVEQLSLSPGQLILILKKNSSgWWLGELQArgkkrQKGWFPASHVKLL 59

Src Homology 3 domain of Saccharomyces cerevisiae Nap1-binding protein 2 and similar fungal proteins; This subfamily includes Saccharomyces cerevisiae Nbp2 (Nucleosome assembly protein 1 (Nap1)-binding protein 2), Schizosaccharomyces pombe Skb5, and similar proteins. Nbp2 interacts with Nap1, which is essential for maintaining proper nucleosome structures in transcription and replication. It is also the binding partner of the yeast type II protein phosphatase Ptc1p and serves as a scaffolding protein that brings seven kinases in close contact to Ptc1p. Nbp2 plays a role many cell processes including organelle inheritance, mating hormone response, cell wall stress, mitotic cell growth at elevated temperatures, and high osmolarity. Skb5 interacts with the p21-activated kinase (PAK) homolog Shk1, which is critical for fission yeast cell viability. Skb5 activates Shk1 and plays a role in regulating cell morphology and growth under hypertonic conditions. Nbp2 and Skb5 contain an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212799 Cd Length: 55 Bit Score: 40.19 E-value: 2.37e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWW--KGEVNGQVGLFPSNYVKL 1169
Cdd:cd11865      1 RAVALYDFEPEHDNELGFAEGQILFILYKHGQGWLiaEDESGGKTGLVPEEFVSY 55

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 40.18 E-value: 2.42e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1035 EIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWegelQARGKKRQIGWFPANYV 1091
Cdd:cd11905      1 EIVVAMYDFQPTEPHDLRLETGEEYVILEKNDVHWW----KARDKYGKEGYIPSNYV 53

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212743 [Multi-domain] Cd Length: 53 Bit Score: 40.08 E-value: 2.54e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11809      1 EATAQFDYTGRSERELSFKKGDSLTLYRQvSDDWWRGQLNGQDGLVPHKYITL 53

Src Homology 3 domain of Melanoma Inhibitory Activity protein and similar proteins; MIA is a single domain protein that adopts a SH3 domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands. MIA is a member of the recently identified family that also includes MIA-like (MIAL), MIA2, and MIA3 (also called TANGO); the biological functions of this family are not yet fully understood.

Pssm-ID: 212694 Cd Length: 76 Bit Score: 40.54 E-value: 2.54e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNK---EDPDWWKGEVNGQ---VGLFPSNYVK 1168
Cdd:cd11760     17 LEDYHGPDCRFLNFKKGDTIYVYSKlagERQDLWAGSVGGDaglFGYFPKNLVQ 70

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 40.30 E-value: 2.56e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1124 YTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNG-----QVGLFPSNYVKL 1169
Cdd:cd11994      8 YVASGVEQLSLSPGQLILILKKNSSGWWLGELQArgkkrQKGWFPASHVKL 58

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 39.73 E-value: 2.56e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTK-KDGDWWTGTVGDKAGVFPS 1010
Cdd:cd11832      2 FIAVKSYSPQEEGEISLHKGDRVKVLSiGEGGFWEGSVRGRTGWFPS 48

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 45.44 E-value: 2.57e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  291 RLPEEPVLEDEQQQLEKKLPVTFEDKK--RENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERE---RQEQE 365
Cdd:TIGR02169  824 LTLEKEYLEKEIQELQEQRIDLKEQIKsiEKEIENLNGKKEELEEELEELEAALRDLESRLGDLKKERDELEaqlRELER 903

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  366 RKRQLELEKQLEKQrelerqreeerrkeIERREAAKRELERQRQLEWERNRRQELlnQRNKEQEDIVVLKAKKKTLEFEL 445
Cdd:TIGR02169  904 KIEELEAQIEKKRK--------------RLSELKAKLEALEEELSEIEDPKGEDE--EIPEEELSLEDVQAELQRVEEEI 967

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  446 EALND------------KKHQLEgkLQDIRCRLTTQRQEIestnksrELRIAEIT 488
Cdd:TIGR02169  968 RALEPvnmlaiqeyeevLKRLDE--LKEKRAKLEEERKAI-------LERIEEYE 1013

Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); MPP5, also called PALS1 (Protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila, is a scaffolding protein which associates with Crumbs homolog 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain. The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells. MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB. Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis. MPP5 contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212969 Cd Length: 63 Bit Score: 40.09 E-value: 2.59e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1122 YDYTAQnDDE--------LAFNKGQIINVLNKEDPDWWK----GEVNGQ--VGLFPS 1164
Cdd:cd12036      6 FDYDPE-DDPyipcrelgLSFQKGDILHVISQEDPNWWQayreGEEDNQslAGLIPS 61

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 40.06 E-value: 2.72e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPGGWWegeLQARGKKRQIGWFPANYVKL 1093
Cdd:cd11858      8 FAGSVANELSLKKDDIVYIVQKEDNGWW---LAKKLDESKEGWVPAAYLEE 55

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212707 [Multi-domain] Cd Length: 57 Bit Score: 40.10 E-value: 2.76e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESqtGEPGWLGGELK-------GKTGWFPANY 758
Cdd:cd11773      2 YKALYDYEPQTEDELTIQEDDILYLLEK--SDDDWWKVKLKvnssdddEPVGLVPATY 57

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 39.95 E-value: 2.77e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  967 AMYTYESSEQG-DLTFQQGDVILVTKK------DGDWWTGTVGD-KAGVFPSNYV 1013
Cdd:cd11771      4 ALYDFTPENPEmELSLKKGDIVAVLSKtdplgrDSEWWKGRTRDgRIGWFPSNYV 58

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 39.97 E-value: 2.78e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQ--QDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11882      1 RARALYACKAEDESELSFEPGQIITNVQPsdEPGWLEGTLNGRTGLIPENYVEF 54

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 40.00 E-value: 2.80e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1040 IASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYV 1091
Cdd:cd11982      6 VKPYQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGR-----VGWFPSDCV 52

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 40.01 E-value: 2.84e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1036 IAQVIASYTATGPEQLTLAPGQLILI-RKKNPGGWWEGELQARgkkrqIGWFPANYVK 1092
Cdd:cd11978      2 IAIARYDFCARDMRELSLLKGDVVKIyTKMSTNGWWRGEVNGR-----VGWFPSTYVE 54

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 40.39 E-value: 2.95e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYVRLK 1016
Cdd:cd11973     22 ALWDHVTMDDQELGFKAGDVIeVMDATNKEWWWGRVLDSEGWFPASFVRLR 72

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 39.76 E-value: 2.96e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1124 YTAQNDDELAFNKGQIINVLNKEDPDWWKG--EVNGQVGLFPSNYVK 1168
Cdd:cd11785      8 YPPQSEAELELKEGDIVFVHKKREDGWFKGtlQRTGKTGLFPGSFVE 54

Src Homology 3 domain of Membrane Protein, Palmitoylated 7 (or MAGUK p55 subfamily member 7); MPP7 is a scaffolding protein that binds to DLG1 and promotes tight junction formation and epithelial cell polarity. Mutations in the MPP7 gene may be associated with the pathogenesis of diabetes and extreme bone mineral density. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212966 Cd Length: 61 Bit Score: 40.00 E-value: 2.96e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1118 VIGMYDYTAQNDDE-------LAFNKGQIINVLNKEDPDWWK----GEVNGQVGLFPSNY 1166
Cdd:cd12033      2 IKALFDYNPNEDKAipckeagLSFKKGDILQIMSQDDATWWQakheGDANPRAGLIPSKH 61

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 39.80 E-value: 2.98e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  963 EEFIAMYTYESSEQGDLTFQQG-DVILVTKKDGDWWTGTvgDK---AGVFPSNYVRLK 1016
Cdd:cd11905      1 EIVVAMYDFQPTEPHDLRLETGeEYVILEKNDVHWWKAR--DKygkEGYIPSNYVTGK 56

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 39.81 E-value: 2.98e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPGGWWEGelQARGKkrqIGWFPANYVKLL 1094
Cdd:cd12073      9 YQGEGDDEISFDPQETITDIEMVDEGWWKG--TCHGH---RGLFPANYVELL 55

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212781 [Multi-domain] Cd Length: 58 Bit Score: 39.85 E-value: 2.99e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDpDWW----KGEVNGQV--GLFPSNYV 1167
Cdd:cd11847      3 KALWDFKARGDEELSFQAGDQFRIAERSG-DWWtalkLDRAGGVVaqGFVPNNYL 56

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 39.59 E-value: 3.02e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd12055      4 VAFSYLPQNEDELELKVGDIIeVVGEVEEGWWEGVLNGKTGMFPSNFIK 52

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 39.91 E-value: 3.13e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKDG---DWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11952      5 ALWDYSAEFPDELSFKEGDMVTVLRKDGegtDWWWASLCGREGYVPRNYFGL 56

Second Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212855 [Multi-domain] Cd Length: 58 Bit Score: 39.97 E-value: 3.15e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNG--QVGLFPSNYVKL 1169
Cdd:cd11922      2 EAIAKFNFNGDTQVEMSFRKGERITLLRQVDENWYEGRIPGtsRQGIFPITYVDV 56

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 39.79 E-value: 3.15e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQ--GQKGWFPKSYV 924
Cdd:cd11889      2 VKAVYSWAGETEGDLGFLEGDLIEVLSIGDgSWWSGKLRrnGAEGIFPSNFV 53

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 39.80 E-value: 3.20e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772  969 YTYESSEQGdLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11829      8 FTGEQHQQG-LSFEAGELIRVLQApDGGWWEGEKDGLRGWFPASYV 52

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212725 [Multi-domain] Cd Length: 59 Bit Score: 39.98 E-value: 3.26e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772 1115 VCQVIgmYDYTAQNDDELAFNKGQIINV----LNKEDPDWWKG--EVNGQVGLFPSNYV 1167
Cdd:cd11791      1 VLRVL--YPYTPQEEDELELVPGDYIYVspeeLDSSSDGWVEGtsWLTGCSGLLPENYT 57

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 39.82 E-value: 3.27e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVK 925
Cdd:cd11870      1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLeGHSDGRVGIFPKCFVV 52

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 39.71 E-value: 3.34e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1036 IAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGElqARGkkrQIGWFPANYVKL 1093
Cdd:cd11959      1 TAVALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGV--CRG---KYGLFPANYVEL 53

Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP bind the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212731 Cd Length: 50 Bit Score: 39.33 E-value: 3.36e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFP 755
Cdd:cd11797      1 YGVALYRFQALEPNELDFEVGDRIRI--IATLEDGWLEGELKGRRGIFP 47

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 39.57 E-value: 3.37e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd12054      2 QCKVLFEYVPQNEDELELKVGDIIDINEEvEEGWWSGTLNGKSGLFPSNFVK 53

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212955 [Multi-domain] Cd Length: 53 Bit Score: 39.44 E-value: 3.40e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1123 DYTAQNDDELAFNKGQIINVLNKEDPDWW---KGEvngQVGLFPSNYVK 1168
Cdd:cd12022      7 AYTAVEEDELTLLEGEAIEVIHKLLDGWWvvrKGE---VTGYFPSMYLQ 52

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 39.82 E-value: 3.44e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  874 LQAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11956      2 VEAVACFDYTGRTAQELSFKRGDVLLLHSKASSdWWRGEHNGMRGLIPHKYISV 55

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 39.81 E-value: 3.48e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd12056      5 KALFHYEGTNEDELDFKEGEIILIISKdtgEPGWWKGELNGKEGVFPDNFVSQ 57

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 44.77 E-value: 3.48e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  299 EDEQQQLEKKLPVTFE--DKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKER-ER-----QEQERKRQL 370
Cdd:PRK12704    81 RNELQKLEKRLLQKEEnlDRKLELLEKREEELEKKEKELEQKQQELEKKEEELEELIEEQLQElERisgltAEEAKEILL 160

                           90
                   ....*....|
gi 1061899772  371 E-LEKQLEKQ 379
Cdd:PRK12704   161 EkVEEEARHE 170

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 39.69 E-value: 3.60e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGelqaRGKKRQIGWFPANYVKL 1093
Cdd:cd11960      2 ARALYDYQAADDTEISFDPGDIITDIEQIDEGWWRG----TGPDGTYGLFPANYVEL 54

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 39.55 E-value: 3.73e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVT-KKDGDWWTGTV-GD--KAGVFPSNYV 1013
Cdd:cd11966      4 ALYNCVADNPDELTFSEGEIIIVDgEEDKEWWIGHIdGEptRRGAFPVSFV 54

Second Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212865 Cd Length: 57 Bit Score: 39.44 E-value: 3.76e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  967 AMYTYE-----SSEQGD-LTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11932      4 ALYNFDlkeknREESKDcLKFQKDDIITVISRvDENWAEGKLGDQVGIFPILFV 57

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 39.37 E-value: 3.78e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKrqiGWFPANYVK 1092
Cdd:cd11785      3 RVIVPYPPQSEAELELKEGDIVFVHKKREDGWFKGTLQRTGKT---GLFPGSFVE 54

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 44.65 E-value: 3.80e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLPvTFEDKKrenfergnlELEKRRQALLEQQRKEQERLAqlERAEQERKERERQEQERKRQLELEKQLE 377
Cdd:PRK02224   487 LEEEVEEVEERLE-RAEDLV---------EAEDRIERLEERREDLEELIA--ERRETIEEKRERAEELRERAAELEAEAE 554

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  378 KQRELerqreeerrkeierreAAKRELERQRQLEW--ERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQL 455
Cdd:PRK02224   555 EKREA----------------AAEAEEEAEEAREEvaELNSKLAELKERIESLERIRTLLAAIADAEDEIERLREKREAL 618

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  456 EGKLQDIRCRLTTQRQEIestnksRELriaeithlqqqlqesqqmlgrlipEKQILNDQLKQVQQNslhrdslvtLKRAL 535
Cdd:PRK02224   619 AELNDERRERLAEKRERK------REL------------------------EAEFDEARIEEARED---------KERAE 659

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1061899772  536 EAKElarqHLRDQLDEVEkETRSKLQ-EIDIFNNQLKELREI 576
Cdd:PRK02224   660 EYLE----QVEEKLDELR-EERDDLQaEIGAVENELEELEEL 696

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 39.55 E-value: 3.89e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYV 1091
Cdd:cd11984      5 AVKAYSPQGEGEIQLNRGERVKVLSIGEGGFWEGTVKGRT-----GWFPADCV 52

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 39.26 E-value: 3.89e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKKDGD--WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11804      1 EAVAKHDFKATAEDELSFKKGSILKVLNMEDDpnWYKAELDGKEGLIPKNYI 52

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 39.52 E-value: 3.91e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKLL 1094
Cdd:cd11921      9 FQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGR-----VGIFPANYVEVL 55

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 39.30 E-value: 3.93e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGE--VQGQKGWFPKSYVKL 926
Cdd:cd11783      4 ALYPYKPQKPDELELRKGEMYTVTEKcQDGWFKGTslRTGQSGVFPGNYVQP 55

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 39.58 E-value: 4.00e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11996      5 AMYDYTANNEDELSFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNYVK 53

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212830 [Multi-domain] Cd Length: 55 Bit Score: 39.59 E-value: 4.04e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGG-ELKGKTGWFPANYAE 760
Cdd:cd11897      3 RALYDFRSENPGEISLREHEVLSLCSEQDIE-GWLEGvNSRGDRGLFPASYVE 54

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 39.60 E-value: 4.09e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK---DGDWWTGTVGDKAGVFPSNY 1012
Cdd:cd11987      4 ALYPFEARSHDEITIQPGDIVMVDESqtgEPGWLGGELKGKTGWFPANY 52

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 39.28 E-value: 4.42e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILV-----TKKDGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd11800      2 YYALYTFEARSPGELSVTEGQVVTVlekhdLKGNPEWWLVEDRGKQGYVPSNYLA 56

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212830 [Multi-domain] Cd Length: 55 Bit Score: 39.20 E-value: 4.68e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM--WWFG-EVQGQKGWFPKSYVKL 926
Cdd:cd11897      1 RARALYDFRSENPGEISLREHEVLSLCSEQDIegWLEGvNSRGDRGLFPASYVEV 55

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 39.23 E-value: 5.03e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKK---DGDWWTGTVGDKAGVFPSNYVrlkDSEG 1020
Cdd:cd11977      4 VARYNFAARDMRELSLREGDVVRIYSRiggDQGWWKGETNGRIGWFPSTYV---EEEG 58

Domain of unknown function (DUF4686); This family of proteins is found in eukaryotes. Proteins in this family are typically between 498 and 775 amino acids in length. There is a conserved DLK sequence motif.

Pssm-ID: 464838 [Multi-domain] Cd Length: 384 Bit Score: 43.90 E-value: 5.05e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  330 KRRQALLEQQRKEQERLAQ-LER-------AEQE-RKERER-----------QEQERKRQLELeKQLEKQRELERQREEE 389
Cdd:pfam15742    2 SSGEKLKYQQQEEVQQLRQnLQRlqilctsAEKElRYERGKnldlkqhnsllQEENIKIKAEL-KQAQQKLLDSTKMCSS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  390 RRKEIerreaaKRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKAK-----KKTLEFE-----------LEALNDKKH 453
Cdd:pfam15742   81 LTAEW------KHCQQKIRELELEVLKQAQSIKSQNSLQEKLAQEKSRvadaeEKILELQqklehahkvclTDTCILEKK 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  454 QLEGK---LQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQIlndqlkQVQQNSLHRDSLVT 530
Cdd:pfam15742  155 QLEERikeASENEAKLKQQYQEEQQKRKLLDQNVNELQQQVRSLQDKEAQLEMTNSQQQL------RIQQQEAQLKQLEN 228

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  531 LKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQL-KELREIHNKQQLQKQKSMEAERLKQKEQER---KIIELE 606
Cdd:pfam15742  229 EKRKSDEHLKSNQELSEKLSSLQQEKEALQEELQQVLKQLdVHVRKYNEKHHHHKAKLRRAKDRLVHEVEQrdeRIKQLE 308

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772  607 KQKEEAQRRAqERDKQWLEHVQQEDEH--QRPRKL----HEEEKL 645
Cdd:pfam15742  309 NEIGILQQQS-EKEKAFQKQVTAQNEIllLEKRKLleqlTEQEEL 352

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212844 [Multi-domain] Cd Length: 55 Bit Score: 39.17 E-value: 5.06e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWW----KGevNGQVGLFPSNYVKL 1169
Cdd:cd11911      1 TCTALYDFDGTSEGTLSMEEGEILLVLEEDGGDGWtrvrKN--NGDEGYVPTSYIEV 55

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 39.31 E-value: 5.11e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  959 VVSGEefiAMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11975      4 IVSAE---AVWDHVTMANRELAFKAGDVIkVLDASNKDWWWGQIDDEEGWFPASFVRL 58

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 39.24 E-value: 5.19e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK---DGDWWTGTVGD-KAGVFPSNYV 1013
Cdd:cd11904      5 ALYPFSSSNDEELNFEKGEVMDVIEKpenDPEWWKCRKANgQVGLVPKNYV 55

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 39.23 E-value: 5.38e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQQD----MWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11954      3 VYALWDYEAQNADELSFQEGDAITILRRKDdsetEWWWARLNDKEGYVPKNLLGL 57

hypothetical protein; Provisional

Pssm-ID: 237178 [Multi-domain] Cd Length: 508 Bit Score: 43.93 E-value: 5.40e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  302 QQQLEKKLPVTFEDKKRENfERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKER---ERQEQERKRQLELEKQLEK 378
Cdd:PRK12705    28 RQRLAKEAERILQEAQKEA-EEKLEAALLEAKELLLRERNQQRQEARREREELQREEErlvQKEEQLDARAEKLDNLENQ 106

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772  379 QRELERQREEERRKEIERREAAKRELERQRQLEWERnRRQELLNQRNKEQEDIVVLKAKKKTLEFELEA 447
Cdd:PRK12705   107 LEEREKALSARELELEELEKQLDNELYRVAGLTPEQ-ARKLLLKLLDAELEEEKAQRVKKIEEEADLEA 174

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 39.17 E-value: 5.43e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  962 GEEFIAMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTV--GDKAGVFPSNYV 1013
Cdd:cd11918      1 RTPYKAVYQYRPQNEDELELREGDRVDVMQQcDDGWFVGVSrrTQKFGTFPGNYV 55

Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); MPP3 is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subdpical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212972 Cd Length: 62 Bit Score: 39.17 E-value: 5.45e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1121 MYDYTAQNDDE-------LAFNKGQIINVLNKEDPDWWK----GEVNGQVGLFPS 1164
Cdd:cd12039      5 LFDYNPYEDRAipcqeagLPFKRRDILEVVSQDDPTWWQakrvGDTNLRAGLIPS 59

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 39.14 E-value: 5.53e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLE---QQDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11952      5 ALWDYSAEFPDELSFKEGDMVTVLRkdgEGTDWWWASLCGREGYVPRNYFGL 56

Src homology 3 domain of Endophilin-B2; Endophilin-B2, also called SH3GLB2 (SH3-domain GRB2-like endophilin B2), is a cytoplasmic protein that interacts with the apoptosis inducer Bax. It is overexpressed in prostate cancer metastasis and has been identified as a cancer antigen with potential utility in immunotherapy. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. Endophilin-B2 forms homo- and heterodimers (with endophilin-B1) through its BAR domain. The related protein endophilin-B1 interacts with amphiphysin 1 and dynamin 1 through its SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212877 Cd Length: 55 Bit Score: 39.21 E-value: 5.74e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINV--LNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11944      5 LYDYEAADSSELALLADELITVysLPGMDPDWLIGERGNQKGKVPVTYLEL 55

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 44.16 E-value: 5.78e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  314 EDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKE 393
Cdd:COG1196    630 ARLEAALRRAVTLAGRLREVTLEGEGGSAGGSLTGGSRRELLAALLEAEAELEELAERLAEEELELEEALLAEEEEEREL 709

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  394 IERREAAKRELERQRQLEWERNR-RQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDI---------- 462
Cdd:COG1196    710 AEAEEERLEEELEEEALEEQLEAeREELLEELLEEEELLEEEALEELPEPPDLEELERELERLEREIEALgpvnllaiee 789

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1061899772  463 --RCR-----LTTQRQEIESTNKSRELRIAEI 487
Cdd:COG1196    790 yeELEerydfLSEQREDLEEARETLEEAIEEI 821

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 38.96 E-value: 5.85e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPA 756
Cdd:cd11832      1 YFIAVKSYSPQEEGEISLHKGDRVKV--LSIGEGGFWEGSVRGRTGWFPS 48

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

Pssm-ID: 464032 [Multi-domain] Cd Length: 221 Bit Score: 42.77 E-value: 5.97e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  329 EKRRQALLEQQRKEQERLAQLERAEQ-ERKERERQEQ--ERKRQLELEKQLEKQRELERQREEERRKEIERREAAkrELE 405
Cdd:pfam13904   63 AKQRQRQKELQAQKEEREKEEQEAELrKRLAKEKYQEwlQRKARQQTKKREESHKQKAAESASKSLAKPERKVSQ--EEA 140

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  406 RQRQLEWERNRRQELLNQRNKEQEDivvlKAKKKTLEFELEALNDKKHQ 454
Cdd:pfam13904  141 KEVLQEWERKKLEQQQRKREEEQRE----QLKKEEEEQERKQLAEKAWQ 185

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 38.78 E-value: 5.99e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11995      5 GMYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGELNGQVGLFPSNYVK 53

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 39.01 E-value: 6.06e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANY 758
Cdd:cd11951      1 FVQAQYDFSAEDPSQLSFRRGDIIEVLDCP--DPNWWRGRISGRVGFFPRNY 50

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 38.86 E-value: 6.20e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEK 761
Cdd:cd12077      3 YVTVQPYTSQGKDEIGFEKGVTVEV--IQKNLEGWWYIRYLGKEGWAPASYLKK 54

C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The C-terminal SH3 domain of CRK has not been shown to bind any target protein; it acts as a negative regulator of CRK function by stabilizing a structure that inhibits the access by target proteins to the N-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212693 [Multi-domain] Cd Length: 57 Bit Score: 39.01 E-value: 6.29e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1034 PEIAQVIASY--TATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYVKL 1093
Cdd:cd11759      1 PAYARVIQKRvpNAYDKTALALEVGDLVKVTKINVSGQWEGEL--NGKV---GHFPFTHVEL 57

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 38.77 E-value: 6.31e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMV--DESQTGEPGWlGGELKGKTGWFPANYAE 760
Cdd:cd11894      1 FVKALYDYEGQTDDELSFPEGAIIRIlnKENQDDDGFW-EGEFNGRIGVFPSVLVE 55

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).

Pssm-ID: 129694 [Multi-domain] Cd Length: 1311 Bit Score: 44.27 E-value: 6.53e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  333 QALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKqLEKQRELERQREEERRKEIERREAAKRELERQRQLEW 412
Cdd:TIGR00606  690 EAELQEFISDLQSKLRLAPDKLKSTESELKKKEKRRDEMLGL-APGRQSIIDLKEKEIPELRNKLQKVNRDIQRLKNDIE 768

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  413 ERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRiaeithlqq 492
Cdd:TIGR00606  769 EQETLLGTIMPEEESAKVCLTDVTIMERFQMELKDVERKIAQQAAKLQGSDLDRTVQQVNQEKQEKQHELD--------- 839

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  493 qlqeSQQMLGRLIpeKQILNDQLKQVQQNSLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKE 572
Cdd:TIGR00606  840 ----TVVSKIELN--RKLIQDQQEQIQHLKSKTNELKSEKLQIGTNLQRRQQFEEQLVELSTEVQSLIREIKDAKEQDSP 913

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  573 LRE------------IHNKQQLQKQKSME----AERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRP 636
Cdd:TIGR00606  914 LETflekdqqekeelISSKETSNKKAQDKvndiKEKVKNIHGYMKDIENKIQDGKDDYLKQKETELNTVNAQLEECEKHQ 993

                          330
                   ....*....|...
gi 1061899772  637 RKLHEEEKLKREE 649
Cdd:TIGR00606  994 EKINEDMRLMRQD 1006

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 38.90 E-value: 6.58e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVL----EQQDMWWFGEVQGQKGWFPKSYVKL 926
Cdd:cd11807      2 VVYALFDYEAENGDELSFREGDELTVLrkgdDDETEWWWARLNDKEGYVPRNLLGL 57

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212742 [Multi-domain] Cd Length: 53 Bit Score: 38.62 E-value: 6.59e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 925
Cdd:cd11808      4 ALYDYQEKSPREVSMKKGDILTLLNSSNKdWWKVEVNDRQGFVPAAYVK 52

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 38.88 E-value: 6.60e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd11796      3 RVLQDLSAQLDEELDLREGDVVTI--TGILDKGWFRGELNGRRGIFPEGF 50

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212872 [Multi-domain] Cd Length: 55 Bit Score: 38.77 E-value: 6.62e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEV--NGQVGLFPSNYVK 1168
Cdd:cd11939      1 QVQCVHPYVSQEPDELSLELADVLNILDKTDDGWIFGERlhDQERGWFPSSVVE 54

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 38.79 E-value: 6.67e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEKI 762
Cdd:cd11919      4 RAKFDFKAQTLKELPLQKGDIVYI--YKQIDQNWYEGEHHGRVGIFPRSYIELL 55

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 38.63 E-value: 6.81e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANYAE 760
Cdd:cd12046      4 ALFSYEASQPEDLEFQKGDVILVLSKVNED--WLEGQCKGKIGIFPSAFVE 52

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 38.79 E-value: 6.84e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772 1038 QVIASYTATG--PEQLTLAPGQLI-LIRKKNpGGWWEGELQARGKKrqiGWFPANYVKL 1093
Cdd:cd11924      2 EAVAQYTFKGdlEVELSFRKGEHIcLIRKVN-ENWYEGRITGTGRQ---GIFPASYVQV 56

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 38.74 E-value: 6.85e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVL-EQQDMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11986      4 ALYRFKALEKDDLDFHPGERITVIdDSNEEWWRGKIGEKTGYFPMNFI 51

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 41.56 E-value: 7.04e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  569 QLKELREIHNKQQLQKQksmEAERLKQKEQERKIIE-LEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKR 647
Cdd:pfam05672   22 QAREQREREEQERLEKE---EEERLRKEELRRRAEEeRARREEEARRLEEERRREEEERQRKAEEEAEEREQREQEEQER 98


                   ..
gi 1061899772  648 EE 649
Cdd:pfam05672   99 LQ 100

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 43.26 E-value: 7.12e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  569 QLKELREIHNKQQLQKQKSMEAERLKQKEQER-KIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQrprKLHEEEKLKR 647
Cdd:PRK09510    79 EQRKKKEQQQAEELQQKQAAEQERLKQLEKERlAAQEQKKQAEEAAKQAALKQKQAEEAAAKAAAAA---KAKAEAEAKR 155


                   ..
gi 1061899772  648 EE 649
Cdd:PRK09510   156 AA 157

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 38.83 E-value: 7.13e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKK---DGDWW-----TGTVgdkaGVFPSNYV 1013
Cdd:cd11767      3 VALYPFTGENDEELSFEKGERLEIIEKpedDPDWWkarnaLGTT----GLVPRNYV 54

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212847 [Multi-domain] Cd Length: 59 Bit Score: 39.03 E-value: 7.27e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772 1038 QVIASYTATG-PEQLTLAPGQLILIRKKNP-GGWWEGELQarGKKRQiGWFPANYVKLL 1094
Cdd:cd11914      4 RAIVSHPAGSnPTLLRFNRGDIITVLVPEArNGWLYGKLE--GSSRQ-GWFPEAYVKAL 59

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 38.51 E-value: 7.41e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11824      1 KYSVLYDYTAQEDDELSISKGDVVAVIEKGEDgWWTVERNGQKGLVPGTYL 51

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 38.45 E-value: 7.49e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWK-GEVNGQVGLFPSNYVK 1168
Cdd:cd11849      5 LYDFKSAEPNTLSFSEGETFLLLERSNAHWWLvTNHSGETGYVPANYVK 53

Alpha helical coiled-coil rod protein (HCR); This family consists of several mammalian alpha helical coiled-coil rod HCR proteins. The function of HCR is unknown but it has been implicated in psoriasis in humans and is thought to affect keratinocyte proliferation.

Pssm-ID: 284517 [Multi-domain] Cd Length: 749 Bit Score: 43.59 E-value: 7.61e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  441 LEFELEALNDKKHQLEGKLQdIRCRLTTQRqeiesTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQL---KQ 517
Cdd:pfam07111  479 LSLELEQLREERNRLDAELQ-LSAHLIQQE-----VGRAREQGEAERQQLSEVAQQLEQELQRAQESLASVGQQLevaRQ 552

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  518 VQQNSlhRDSLVTLKRAL-EAKELARQHLRDQLDEVEKETRSKLQEIDifnNQLKELREIHNKQQLQ-KQKSMEAERLKQ 595
Cdd:pfam07111  553 GQQES--TEEAASLRQELtQQQEIYGQALQEKVAEVETRLREQLSDTK---RRLNEARREQAKAVVSlRQIQHRATQEKE 627

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  596 KEQERKIIELEKQKEEAQRRAQ-----ERDKQ-WLEHVQQEDEHQRPRK 638
Cdd:pfam07111  628 RNQELRRLQDEARKEEGQRLARrvqelERDKNlMLATLQQEGLLSRYKQ 676

RIB43A; This family consists of several RIB43A-like eukaryotic proteins. Ciliary and flagellar microtubules contain a specialized set of protofilaments, termed ribbons, that are composed of tubulin and several associated proteins. RIB43A was first characterized in the unicellular biflagellate, Chlamydomonas reinhardtii although highly related sequences are present in several higher eukaryotes including humans. The function of this protein is unknown although the structure of RIB43A and its association with the specialized protofilament ribbons and with basal bodies is relevant to the proposed role of ribbons in forming and stabilising doublet and triplet microtubules and in organizing their three-dimensional structure. Human RIB43A homologs could represent a structural requirement in centriole replication in dividing cells.

Pssm-ID: 461780 [Multi-domain] Cd Length: 372 Bit Score: 43.35 E-value: 7.63e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  338 QQRKEQERLAQLERAEQERKER----------------ERQEQERKRQLELEKQLEKQRELERQREEERRKEIErreaaK 401
Cdd:pfam05914    1 VDLKEAAAIERRRQREEERKSRifnarnrtigvdvealDKQVEEKKRQEAAEKAREEAFAEEMVQNDKIALMLE-----K 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  402 RELERQRQLEWE----RNRRQELLNQRNKEQEDIVVLKAKKKTLE--------------FELEALNDKKHQLEGKLQdIR 463
Cdd:pfam05914   76 REEEDRRRLNKElnefRQQHQRPETRREFDLNDPDALKKDLPARVsdddprcgpssmqkFEGEDLNREERKKLQQEQ-MR 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  464 CRLTTQRQEIESTNKSRelRIAEITHlqqqlqesqqmlgrlipEKQILNDQLKQVQQNSLHRDSlvtlKRALeAKELARQ 543
Cdd:pfam05914  155 EWLEQQIEEKKQAEEEE--KHAELLY-----------------DQKRLERDRRALELAKLEEEC----RRAV-NAATKNF 210

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  544 HLRDQLDEVEKETRSKLQEidifnnQLKELREIH----------NKQQLQKQ-----------KSMEAERLK--QKEQER 600
Cdd:pfam05914  211 NQALAAEQAERRRLEKRQE------QEDNLAEIYnhltsdllteNPEVAQSSlgphrvipdrwKGMSPEQLKeiRKEQEQ 284

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  601 KIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRprklhEEEKLKRE 648
Cdd:pfam05914  285 QREEKERRREEEKQRDAEWDRQRLELARAALLLER-----EQQRLRRE 327

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212692 [Multi-domain] Cd Length: 55 Bit Score: 38.50 E-value: 7.70e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  963 EEFIAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGD-KAGVFPSNYV 1013
Cdd:cd11758      1 EYVRALFDFPGNDDEDLPFKKGEILTVIRKPEEqWWNARNSEgKTGMIPVPYV 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 38.39 E-value: 7.74e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPAN 757
Cdd:cd11984      5 AVKAYSPQGEGEIQLNRGERVKV--LSIGEGGFWEGTVKGRTGWFPAD 50

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 38.59 E-value: 7.89e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1040 IASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYV 1091
Cdd:cd12017      5 IGEFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKE-----GWAPSSYI 51

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 38.62 E-value: 8.13e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11947      1 EARGKFDFTASGEDELSFKKGDVLKILSSDDIWFKAELNGEEGYVPKNFV 50

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 38.53 E-value: 8.15e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGE--LKGKTGWFPANY 758
Cdd:cd11783      2 YVALYPYKPQKPDELELRKGEMYTVTEKC--QDGWFKGTslRTGQSGVFPGNY 52

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 38.53 E-value: 8.16e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILV-TKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11806      1 EYVAIADFVATDDSQLSFESGDKLLVlRKPSVDWWWAEHNGCCGYIPASHL 51

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 38.77 E-value: 8.16e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  187 KYRQLFNSHDKTMSGHLT----GPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAM 246
Cdd:pfam13499    3 KLKEAFKLLDSDGDGYLDveelKKLLRKLEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

Pssm-ID: 464032 [Multi-domain] Cd Length: 221 Bit Score: 42.38 E-value: 8.22e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  513 DQLKQVQQNSLHRDSLVT------LKRALEAKELARQHLRDQLDEVEKETRSKLqeidifnNQLKELREIHNKQQLQKQK 586
Cdd:pfam13904   39 TYARKLEGLKLERQPLEAyenwlaAKQRQRQKELQAQKEEREKEEQEAELRKRL-------AKEKYQEWLQRKARQQTKK 111

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  587 SMEAERLKQKEQERKIIELEKqKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREE 649
Cdd:pfam13904  112 REESHKQKAAESASKSLAKPE-RKVSQEEAKEVLQEWERKKLEQQQRKREEEQREQLKKEEEE 173

First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212948 Cd Length: 53 Bit Score: 38.55 E-value: 8.32e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWW----EGELqargkkrqiGWFPANY 1090
Cdd:cd12015      4 VVADYKKQQPNEISLRAGDVVDVIEKNENGWWfvslEDEQ---------GWVPATY 50

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 42.98 E-value: 8.67e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  299 EDEQQQLEKKLpvtfedKKRENFERGNLE--LEKRRQALLEQQRKEQERLAQLER-AEQERKERERQEQERKRQLELEKQ 375
Cdd:pfam13868  221 QKEREEAEKKA------RQRQELQQAREEqiELKERRLAEEAEREEEEFERMLRKqAEDEEIEQEEAEKRRMKRLEHRRE 294

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772  376 LEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQEL 420
Cdd:pfam13868  295 LEKQIEEREEQRAAEREEELEEGERLREEEAERRERIEEERQKKL 339

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 43.75 E-value: 8.69e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  300 DEQQQLEKKLPVTFEDKKREnfergnlELEKRRQALLEQQRKEQERLAQLERAEQERKERER------------------ 361
Cdd:COG4913    272 AELEYLRAALRLWFAQRRLE-------LLEAELEELRAELARLEAELERLEARLDALREELDeleaqirgnggdrleqle 344

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  362 QEQERkrqleLEKQLEKQRELERQREEERRKEIERREAAKRELERQRQ-----LEWERNRRQELLNQRNKEQEDIVVLKA 436
Cdd:COG4913    345 REIER-----LERELEERERRRARLEALLAALGLPLPASAEEFAALRAeaaalLEALEEELEALEEALAEAEAALRDLRR 419

                          170       180       190
                   ....*....|....*....|....*....|
gi 1061899772  437 KKKTLEFELEALNDKKHQLEGKLQDIRCRL 466
Cdd:COG4913    420 ELRELEAEIASLERRKSNIPARLLALRDAL 449

Periplasmic chaperone for outer membrane proteins, Skp family [Cell wall/membrane/envelope biogenesis, Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 442073 [Multi-domain] Cd Length: 171 Bit Score: 41.36 E-value: 8.85e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLpvtfeDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLE 377
Cdd:COG2825     48 LEKEFKKRQAEL-----QKLEKELQALQEKLQKEAATLSEEERQKKERELQKKQQELQRKQQEAQQDLQKRQQELLQPIL 122


                   ..
gi 1061899772  378 KQ 379
Cdd:COG2825    123 EK 124

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 38.67 E-value: 8.97e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKK--DGDWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd12053      1 EYIVEYDYDAVHEDELTIRVGEIIRNVKKleEEGWLEGELNGRRGMFPDNFVK 53

Src Homology 3 domain of Cdc42-Interacting Protein 4, Bzz1 and similar domains; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4) and similar proteins such as Formin Binding Protein 17 (FBP17) and FormiN Binding Protein 1-Like (FNBP1L), as well as yeast Bzz1 (or Bzz1p). CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. Bzz1 is also a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Members of this subfamily contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain as well as at least one C-terminal SH3 domain. Bzz1 contains a second SH3 domain at the C-terminus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212711 [Multi-domain] Cd Length: 55 Bit Score: 38.36 E-value: 8.99e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGDVILVTKKD-GDWWTGTVGDKA--GVFPSNYVRL 1015
Cdd:cd11777      1 ECKALYAFVGSSEGTISMTEGEKLSLVEEDkGDGWTRVRRDTGeeGYVPTSYIRI 55

Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); MPP2 is a scaffolding protein that interacts with the non-receptor tyrosine kinase c-Src in epithelial cells to negatively regulate its activity and morphological function. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212970 Cd Length: 59 Bit Score: 38.78 E-value: 9.06e-04

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1061899772 1132 LAFNKGQIINVLNKEDPDWWKG--EVNGQVGLFPS 1164
Cdd:cd12037     23 LKFRAGDLLQIVNQEDPNWWQAchVEGGSAGLIPS 57

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 38.39 E-value: 9.24e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1119 IGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11984      4 IAVKAYSPQGEGEIQLNRGERVKVLSIGEGGFWEGTVKGRTGWFPADCV 52

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 38.65 E-value: 9.30e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQ------DMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11876      4 ALFDYDARGEDELTLRRGQPVEVLSKDaavsgdEGWWTGKIGDKVGIFPSNYV 56

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 38.59 E-value: 9.56e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQ------DMWWFGEVQGQKGWFPKSYV 924
Cdd:cd12059      4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsgdEGWWTGKINDRVGIFPSNYV 56

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 38.47 E-value: 9.75e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLG-GELKGKTGWFPANY 758
Cdd:cd11904      4 QALYPFSSSNDEELNFEKGEVMDVIEKPENDPEWWKcRKANGQVGLVPKNY 54

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 43.63 E-value: 1.00e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  290 QRLPEEPVLEDEQQQLEKKLPVTFEDKkRENFERGNLELEKRRQALLEQQRKEQERLAQLEraeQERKERERQEQERKRQ 369
Cdd:pfam01576   36 QQLCEEKNALQEQLQAETELCAEAEEM-RARLAARKQELEEILHELESRLEEEEERSQQLQ---NEKKKMQQHIQDLEEQ 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  370 LELEK------QLEKQRELERQREEERRKEIERREAAKRELERQ----------RQLEWERNRRQELLNQRNKEQEDIVV 433
Cdd:pfam01576  112 LDEEEaarqklQLEKVTTEAKIKKLEEDILLLEDQNSKLSKERKlleeriseftSNLAEEEEKAKSLSKLKNKHEAMISD 191

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  434 LKAKKKTLEFELEALNDKKHQLEGKLQDIR---CRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQI 510
Cdd:pfam01576  192 LEERLKKEEKGRQELEKAKRKLEGESTDLQeqiAELQAQIAELRAQLAKKEEELQAALARLEEETAQKNNALKKIRELEA 271

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  511 LNDQLKQ-VQQNSLHRDSLVTLKRAL-EAKELARQHLRDQLDE--VEKETRSKL-QEIDIFNNQLKELREIHNKQ-QLQK 584
Cdd:pfam01576  272 QISELQEdLESERAARNKAEKQRRDLgEELEALKTELEDTLDTtaAQQELRSKReQEVTELKKALEEETRSHEAQlQEMR 351

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  585 QKSMEA-----ERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRpRKLH---EEEKLKREESvkkkdg 656
Cdd:pfam01576  352 QKHTQAleeltEQLEQAKRNKANLEKAKQALESENAELQAELRTLQQAKQDSEHKR-KKLEgqlQELQARLSES------ 424

                          410
                   ....*....|....*
gi 1061899772  657 eEKGKQEAQDKLGRL 671
Cdd:pfam01576  425 -ERQRAELAEKLSKL 438

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 38.40 E-value: 1.01e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQ---KGWFPKSYV 924
Cdd:cd11966      1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKeWWIGHIDGEptrRGAFPVSFV 54

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 38.40 E-value: 1.01e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGG--ELKGKTGWFPANY 758
Cdd:cd11918      4 YKAVYQYRPQNEDELELREGDRVDV--MQQCDDGWFVGvsRRTQKFGTFPGNY 54

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 38.12 E-value: 1.02e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGElqargKKRQIGWFPANYVKL 1093
Cdd:cd11824      2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVE-----RNGQKGLVPGTYLEK 53

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 38.47 E-value: 1.03e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGGELKGKTGWFPANYAE 760
Cdd:cd11946      5 AKYDFKATADDELSFKRGDILKVLNEECDQ-NWYKAELNGKDGFIPKNYIE 54

Nop53 (60S ribosomal biogenesis); This nucleolar family of proteins are involved in 60S ribosomal biogenesis. They are specifically involved in the processing beyond the 27S stage of 25S rRNA maturation. This family contains sequences that bear similarity to the glioma tumour suppressor candidate region gene 2 protein (p60). This protein has been found to interact with herpes simplex type 1 regulatory proteins.

Pssm-ID: 462259 [Multi-domain] Cd Length: 353 Bit Score: 42.67 E-value: 1.03e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  326 LELEKRRQALLEQQRKEQERLAQLERAEQERK-----ERERQEQERKRQLELEKQLEKQrelerqreeerrkeierreaa 400
Cdd:pfam07767  209 KKRLKEEEKLERVLEKIAESAATAEAREEKRKtkaqrNKEKRRKEEEREAKEEKALKKK--------------------- 267

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  401 KRELERQRQLewernrRQELLNQRNKEQEDIVVLKAKKKTLEFELEALndKKHQLeGKLQ 460
Cdd:pfam07767  268 LAQLERLKEI------AKEIAEKEKEREEKAEARKREKRKKKKEEKKL--RPRKL-GKHK 318

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 38.45 E-value: 1.04e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1040 IASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYVKLLS 1095
Cdd:cd11972      8 IYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNG-----VTGLFPGNYVESIM 58

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ARHGEF16, also called ephexin-4, acts as a GEF for RhoG, activating it by exchanging bound GDP for free GTP. RhoG is a small GTPase that is a crucial regulator of Rac in migrating cells. ARHGEF16 interacts directly with the ephrin receptor EphA2 and mediates cell migration and invasion in breast cancer cells by activating RhoG. ARHGEF26, also called SGEF (SH3 domain-containing guanine exchange factor), also activates RhoG. It is highly expressed in liver and may play a role in regulating membrane dynamics. ARHGEF16 and ARHGEF26 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212871 Cd Length: 55 Bit Score: 38.29 E-value: 1.04e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKrqiGWFPANYVK 1092
Cdd:cd11938      3 EIIKAYTAKQPDELSLQQADVVLVLQTESDGWYYGERLRDGER---GWFPSSCAK 54

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 38.38 E-value: 1.05e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILV----TKKDGDWWTGTVGDKAGVFPS 1010
Cdd:cd11894      4 ALYDYEGQTDDELSFPEGAIIRIlnkeNQDDDGFWEGEFNGRIGVFPS 51

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 38.46 E-value: 1.07e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPGGWWEGElqargKKRQIGWFPANYV 1091
Cdd:cd11963     10 FEAVEDNELTFKHGEIIIVLDDSDANWWKGE-----NHRGVGLFPSNFV 53

C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The C-terminal SH3 domain of CRK has not been shown to bind any target protein; it acts as a negative regulator of CRK function by stabilizing a structure that inhibits the access by target proteins to the N-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212693 [Multi-domain] Cd Length: 57 Bit Score: 38.24 E-value: 1.08e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1111 ALAAVCQ--VIGMYDYTAqnddeLAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd11759      2 AYARVIQkrVPNAYDKTA-----LALEVGDLVKVTKINVSGQWEGELNGKVGHFPFTHVEL 57

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 37.95 E-value: 1.10e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGE--VQGQKGWFPKSY 923
Cdd:cd11845      4 ALYDYEARTDDDLSFKKGDRLQILDDsDGDWWLARhlSTGKEGYIPSNY 52

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 38.06 E-value: 1.10e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGE-VQGQKGWFPKSYVKL 926
Cdd:cd11767      2 VVALYPFTGENDEELSFEKGERLEIIEKpedDPDWWKARnALGTTGLVPRNYVEV 56

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 37.93 E-value: 1.13e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVK 925
Cdd:cd11815      1 HAVVLHDFPAEHSDDLSLNSGEIVYLLEKIDTEWYrGKCKNTTGIFPANHVK 52

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212890 Cd Length: 52 Bit Score: 37.97 E-value: 1.14e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1117 QVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11957      1 EVKALCHHIATEPGQLSFNKGDILQVLSRADGDWLRCSLGPDSGLVPIAYV 51

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 38.05 E-value: 1.16e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANY 758
Cdd:cd12055      3 QVAFSYLPQNEDELELKVGDIIEVVGEV--EEGWWEGVLNGKTGMFPSNF 50

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 38.16 E-value: 1.18e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGepgWLGGELKGKTGWFPANYAE 760
Cdd:cd11989      3 QALYPWRAKKDNHLNFNKNDVITVLEQQDM---WWFGEVQGQKGWFPKSYVK 51

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 43.09 E-value: 1.18e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  401 KRELERQR-QLEWERNRRQELL----NQRNKEQEDIVVLKAKK---KTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQE 472
Cdd:TIGR04523  168 KEELENELnLLEKEKLNIQKNIdkikNKLLKLELLLSNLKKKIqknKSLESQISELKKQNNQLKDNIEKKQQEINEKTTE 247

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  473 IESTNKSRELRIAEITHLQQQLQESQQMLGRliPEKQI--LNDQLKQVQ------QNSLHRDSLVTLKRALEAKELARQH 544
Cdd:TIGR04523  248 ISNTQTQLNQLKDEQNKIKKQLSEKQKELEQ--NNKKIkeLEKQLNQLKseisdlNNQKEQDWNKELKSELKNQEKKLEE 325

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  545 LRDQLDEVEKETRSKLQEIDIFNNQL-----------KELREIHNK-QQLQKQKSMEAERLKQKEQERKIIE--LEKQKE 610
Cdd:TIGR04523  326 IQNQISQNNKIISQLNEQISQLKKELtnsesensekqRELEEKQNEiEKLKKENQSYKQEIKNLESQINDLEskIQNQEK 405

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772  611 EAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEK-----LKREESV 651
Cdd:TIGR04523  406 LNQQKDEQIKKLQQEKELLEKEIERLKETIIKNNseikdLTNQDSV 451

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 38.07 E-value: 1.21e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIV--MVDESQTGepgWLGGEL--KGKTGWFPANYAEK 761
Cdd:cd11779      4 KALYPHAAGGETQLSFEEGDVItlLGPEPRDG---WHYGENerSGRRGWFPIAYTEP 57

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 42.44 E-value: 1.22e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLPVTFEDKKRENFERGNLE-----LEKRRQALLEQQRKEQERLAQLERAEQE-RKERERQEQERKRQL- 370
Cdd:COG4942     32 LQQEIAELEKELAALKKEEKALLKQLAALErriaaLARRIRALEQELAALEAELAELEKEIAElRAELEAQKEELAELLr 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  371 --------------------------------------ELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQ-LE 411
Cdd:COG4942    112 alyrlgrqpplalllspedfldavrrlqylkylaparrEQAEELRADLAELAALRAELEAERAELEALLAELEEERAaLE 191

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772  412 WERNRRQELLNQrnkeqedivvLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSR 480
Cdd:COG4942    192 ALKAERQKLLAR----------LEKELAELAAELAELQQEAEELEALIARLEAEAAAAAERTPAAGFAA 250

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212859 [Multi-domain] Cd Length: 55 Bit Score: 38.03 E-value: 1.27e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESqtGEPGWLGGEL--KGKTGWFPANY 758
Cdd:cd11926      2 YVAIYPYTPRKEDELELRKGEMFLVFER--CQDGWFKGTSmhTSKIGVFPGNY 52

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 38.09 E-value: 1.28e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772  712 YPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANY 758
Cdd:cd11901      8 FNYTAEREDELSLVKGTKVIVMEKCSD--GWWRGSYNGQVGWFPSNY 52

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 38.10 E-value: 1.29e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGgWWEGELqaRGKKrqiGWFPANYVKL 1093
Cdd:cd11990      2 AQALCSWTAKKDNHLNFSKNDIITVLEQQEN-WWFGEV--HGGR---GWFPKSYVKL 52

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 38.08 E-value: 1.33e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGK-TGWFPANYAEK 761
Cdd:cd11825      3 KALYDYRAQRPDELSFCKHAIITNVEKEDG--GWWRGDYGGKkQKWFPANYVEE 54

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 37.83 E-value: 1.34e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKKDGDWW---TGTVGDKAGVFPSNYV 1013
Cdd:cd11784      2 CVALHSYSAHRPEELELQKGEGVRVLGKFQEGWlrgLSLVTGRVGIFPSNYV 53

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 38.05 E-value: 1.35e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  705 VVYYRALYPFESRSHDEITIQPGDIvmVDESQTGEPGWLGGELK--GKTGWFPANYAE 760
Cdd:cd11916      1 AYSYQALYSYAPQNDDELELRDGDI--VDVMEKCDDGWFVGTSRrtKQFGTFPGNYVK 56

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212932 [Multi-domain] Cd Length: 56 Bit Score: 38.00 E-value: 1.36e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  706 VYYRALYPFESRSHDEITIQPGDIVMVDESQTgEPGWLGG-ELKGKTGWFPANYAE 760
Cdd:cd11999      2 VRVRAVYDYTGQEPDELSFKAGEELLKVEDED-EQGWCKGvTDGGAVGLYPANYVE 56

Second Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212864 Cd Length: 55 Bit Score: 37.98 E-value: 1.41e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772 1120 GMYDYTAQNDDE----LAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11931      4 ALYDFEIKDKDQdkdcLTFTKDEILTVIRRVDENWAEGMLGDKIGIFPILYV 55

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 42.70 E-value: 1.44e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  415 NRRQELLNQRNKEQEDIVVLKAKKKTLEFEL-------EALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEI 487
Cdd:TIGR04523   33 TEEKQLEKKLKTIKNELKNKEKELKNLDKNLnkdeekiNNSNNKIKILEQQIKDLNDKLKKNKDKINKLNSDLSKINSEI 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  488 THLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDSLVTLKRAlEAKELARQ--HLRDQLDEVEKETRSKLQEIDI 565
Cdd:TIGR04523  113 KNDKEQKNKLEVELNKLEKQKKENKKNIDKFLTEIKKKEKELEKLNN-KYNDLKKQkeELENELNLLEKEKLNIQKNIDK 191

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  566 FNNQL--KELREIHNKQQLQKQKSMEAERLKQKEQErkiIELEKQKEEAQRRAQERDKQwLEHVQQE 630
Cdd:TIGR04523  192 IKNKLlkLELLLSNLKKKIQKNKSLESQISELKKQN---NQLKDNIEKKQQEINEKTTE-ISNTQTQ 254

Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212856 [Multi-domain] Cd Length: 57 Bit Score: 37.97 E-value: 1.44e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  964 EFIAMYTYESSEQGDLTFQQGD-VILVTKKDGDWWTGTV--GDKAGVFPSNYVRL 1015
Cdd:cd11923      2 EAVAKYNFNADTNVELSLRKGDrVVLLKQVDQNWYEGKIpgTNRQGIFPVSYVEV 56

DDRGK domain; This is a family of proteins of approximately 300 residues, found in plants and vertebrates. They contain a highly conserved DDRGK motif.

Pssm-ID: 370664 [Multi-domain] Cd Length: 188 Bit Score: 41.18 E-value: 1.46e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  329 EKRRQALLEQQRKEQERLAQleraEQERKERERQEQERKRQLELEKqlekqrelerqreeerrkeierreaAKRELERQR 408
Cdd:pfam09756    5 AKKRAKLELKEAKRQQREAE----EEEREEREKLEEKREEEYKERE-------------------------EREEEAEKE 55

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  409 QLEWERNRRQEllnQRNKEQEDIVVLKAkkktlEFELEALNDKKHQLEGKLQDIRC 464
Cdd:pfam09756   56 KEEEERKQEEE---QERKEQEEYEKLKS-----QFVVEEEGTDKLSAEDESQLLED 103

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 38.08 E-value: 1.48e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1040 IASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQargkkRQIGWFPANYVK 1092
Cdd:cd11971      5 IYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCN-----GVTGLFPGNYVE 52

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 38.06 E-value: 1.56e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  873 GLQAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQ--GQKGWFPKSYVKLI 927
Cdd:cd11933      1 GKSFRAMYDYRAADDDEVSFKDGDTIVNVQTIDEgWMYGTVQrtGKTGMLPANYVEAI 58

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 40.16 E-value: 1.58e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  175 VAEWAVPQSSRLKYRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMH 247
Cdd:COG5126     58 GMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGVSEEEADELFARLDTDGDGKISFEEFVAAVR 130

Transcriptional activator LAG-3; The C.elegans Notch pathway, involved in the control of growth, differentiation and patterning in animal development, relies on either of the receptors GLP-1 or LIN-12. Both these receptors promote signalling by the recruitment of LAG-3 to target promoters, where it then acts as a transcriptional activator. LAG-3 works as a ternary complex together with the DNA binding protein, LAG-1. Its N-terminal region adopts an elongated kinked helix that is required for complex assembly.

Pssm-ID: 151935 [Multi-domain] Cd Length: 476 Bit Score: 42.64 E-value: 1.59e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  569 QLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQE--RDKQWLEHVQQEDE-----------HQR 635
Cdd:pfam11498  321 HIAQLAQQQNKMRLLQQQEMEMQRIEQQRQQQIMHQHQQQQQQEHQQQQMllQQQQQMHQLQQHHQmngggqfatqaHQH 400

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772  636 PRKLHEEEKLKREESVKKKDGEEKGKQEAQdklgrlfHQHQEPAK 680
Cdd:pfam11498  401 AAYLQQMQHMRLQEQIQHQQQQAQHHQQAQ-------QQHQQPAQ 438

Guanylate-binding protein, C-terminal domain; Transcription of the anti-viral guanylate-binding protein (GBP) is induced by interferon-gamma during macrophage induction. This family contains GBP1 and GPB2, both GTPases capable of binding GTP, GDP and GMP.

Pssm-ID: 460721 [Multi-domain] Cd Length: 297 Bit Score: 41.89 E-value: 1.63e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  526 DSLVTLKRALEAKELARQHLRDQLDEVEKETRSkLQEIDIFNNQLKELREIHNKQQL-QKQKSMEAER----------LK 594
Cdd:pfam02841  190 EAILQTDQALTAKEKAIEAERAKAEAAEAEQEL-LREKQKEEEQMMEAQERSYQEHVkQLIEKMEAEReqllaeqermLE 268

                           90       100
                   ....*....|....*....|....
gi 1061899772  595 QKEQERKIIELEKQKEEAQRRAQE 618
Cdd:pfam02841  269 HKLQEQEELLKEGFKTEAESLQKE 292

N-terminal (or first) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. The N-terminal SH3 domain increases the affinity of p67phox for the oxidase complex. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212804 Cd Length: 54 Bit Score: 37.57 E-value: 1.65e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVK 1168
Cdd:cd11871      5 LYEFVPETKEELQVLPGNIVFVLKKGTDNWATVVFNGKKGLVPCNFLE 52

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 37.68 E-value: 1.65e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd11977      3 AVARYNFAARDMRELSLREGDVVRIYSRiggDQGWWKGETNGRIGWFPSTYVE 55

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212926 Cd Length: 65 Bit Score: 38.18 E-value: 1.67e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGEL-----KGKTGWFPANYAE 760
Cdd:cd11993      7 QVIASYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELqargkKRQIGWFPANYVK 61

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 37.91 E-value: 1.71e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  187 KYRQLFNSHDKTMSGHLTGPQARTIL--MQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMH 247
Cdd:cd00051      1 ELREAFRLFDKDGDGTISADELKAALksLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212874 Cd Length: 57 Bit Score: 37.58 E-value: 1.75e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  710 ALYPFESRSHDEITIQPGDIVMVDESQ--TGEPGWLGGELKGKTGWFPANY 758
Cdd:cd11941      4 AAYPFTARSKHEVSLQAGQPVTVLEPHdkKGSPEWSLVEVNGQRGYVPSSY 54

Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212946 Cd Length: 61 Bit Score: 37.74 E-value: 1.75e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772  966 IAMYTYESSE-------QGDLTFQQGDVILV---TKKDGdWWTGTVGDKAGVFPSNYVR 1014
Cdd:cd12013      3 VALFDYDPREsspnvdaEVELSFRAGDIITVfgeMDEDG-FYYGELNGQRGLVPSNFLE 60

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212695 [Multi-domain] Cd Length: 57 Bit Score: 37.73 E-value: 1.78e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1034 PEIAQVIASYTATGPEQLTLAPGQLI-LIRKKNPGGWwegeLQARGKKRQIGWFPANYVKL 1093
Cdd:cd11761      1 PVTCKVLYSYEAQRPDELTITEGEELeVIEDGDGDGW----VKARNKSGEVGYVPENYLQF 57

Src homology 3 domain of Src-Like Adaptor Proteins; SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. Vertebrates contain two SLAPs, named SLAP (or SLA1) and SLAP2 (or SLA2). SLAP has been shown to interact with the EphA receptor, EpoR, Lck, PDGFR, Syk, CD79a, among others, while SLAP2 interacts with CSF1R. Both SLAPs interact with c-Cbl, LAT, CD247, and Zap70. SLAP modulates TCR surface expression levels as well as surface and total BCR levels. As an adaptor to c-Cbl, SLAP increases the ubiquitination, intracellular retention, and targeted degradation of the BCR complex components. SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212782 Cd Length: 55 Bit Score: 37.55 E-value: 1.80e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772 1121 MYDYTAQNDDELAFNKGQIINVLNkEDPDWWK--GEVNGQVGLFPSNYV 1167
Cdd:cd11848      5 LGDYPSGGPAELSLRLGEPLTIVS-DEGDWWKvlSEVTGRESYIPSVHV 52

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 42.59 E-value: 1.80e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  305 LEKklPVTFE--DKKRENFE-----RGNLELEKRRQALLEQQRKEQERLA----QLERAEQERKERERQEQERKRQLeLE 373
Cdd:COG4913    218 LEE--PDTFEaaDALVEHFDdleraHEALEDAREQIELLEPIRELAERYAaareRLAELEYLRAALRLWFAQRRLEL-LE 294

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  374 KQLEKqrelerqreeeRRKEIERREAAKRELERQRQLEweRNRRQELLNQRNKEQ-EDIVVLKAKKKTLEFELEALNDKK 452
Cdd:COG4913    295 AELEE-----------LRAELARLEAELERLEARLDAL--REELDELEAQIRGNGgDRLEQLEREIERLERELEERERRR 361

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  453 HQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEIThlqQQLQESQQMLGRLIPEKQILNDQLKQVQQ--NSL-HRDSLV 529
Cdd:COG4913    362 ARLEALLAALGLPLPASAEEFAALRAEAAALLEALE---EELEALEEALAEAEAALRDLRRELRELEAeiASLeRRKSNI 438

                          250       260
                   ....*....|....*....|....
gi 1061899772  530 TlKRALEAKELARQHLrdQLDEVE 553
Cdd:COG4913    439 P-ARLLALRDALAEAL--GLDEAE 459

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212709 [Multi-domain] Cd Length: 57 Bit Score: 37.68 E-value: 1.80e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772 1035 EIAQVIASYTATGPEQLTLAPGQ-LILIRKKNPGGWWEGELQARGKKrqiGWFPANYVKL 1093
Cdd:cd11775      1 KRGKVLYDFDAQSDDELTVKEGDvVYILDDKKSKDWWMVENVSTGKE---GVVPASYIEI 57

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 37.69 E-value: 1.81e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVT------KKDGDWWTGTVGD--KAGVFPSNYVR 1014
Cdd:cd11790      7 ATHDYTAEDTDELTFEKGDVILVIpfddpeEQDEGWLMGVKEStgCRGVFPENFTE 62

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 37.67 E-value: 1.81e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVK 1092
Cdd:cd12055      3 QVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGK-----TGMFPSNFIK 52

Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function. The related myosin XVa is important for normal growth of mechanosensory stereocilia of inner ear hair cells. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 213001 Cd Length: 55 Bit Score: 37.55 E-value: 1.82e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772 1118 VIGMYDYTAQNDDELAFNKGQIINVLNKE--DPDWWKGEVNGQVGLFPSNYVKL 1169
Cdd:cd12068      2 VVALRSYITDDKSLLSFHRGDLIKLLPMAglEPGWQFGSTGGRSGLFPADIVQP 55

DNA damage checkpoint protein; This is a family of proteins which regulate checkpoint kinases. In Schizosaccharomyces pombe this protein is called Rad26 and in Saccharomyces cerevisiae it is called LCD1.

Pssm-ID: 462906 Cd Length: 615 Bit Score: 42.31 E-value: 1.85e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  545 LRDQLDEVEKEtrsKLQEIDIFNNQLKELREiHNKQQLQKQKSmEAERLkqkEQERKIIELEKQK 609
Cdd:pfam09798    2 LRDKLELLQQE---KEKELEKLKNSYEELKS-SHEEELEKLKQ-EVQKL---EDEKKFLLNELRS 58

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 37.68 E-value: 1.90e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772  969 YTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11902      7 FAYVAEREDELSLVKGSRVTVMEKCSDgWWRGSYNGQIGWFPSNYV 52

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 37.56 E-value: 2.00e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGE-PGWLGGELKGKTGWFPANYAEKIPE 764
Cdd:cd12003      4 KALYDNAAESPEELSFRRGDVLMVLKREHGSlPGWWLCSLHGQQGIAPANRLRLLPT 60

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ARHGEF16, also called ephexin-4, acts as a GEF for RhoG, activating it by exchanging bound GDP for free GTP. RhoG is a small GTPase that is a crucial regulator of Rac in migrating cells. ARHGEF16 interacts directly with the ephrin receptor EphA2 and mediates cell migration and invasion in breast cancer cells by activating RhoG. ARHGEF26, also called SGEF (SH3 domain-containing guanine exchange factor), also activates RhoG. It is highly expressed in liver and may play a role in regulating membrane dynamics. ARHGEF16 and ARHGEF26 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212871 Cd Length: 55 Bit Score: 37.52 E-value: 2.06e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  714 FESRSHDEITIQPGDIVMVdeSQTGEPGWLGGEL--KGKTGWFPANYAE 760
Cdd:cd11938      8 YTAKQPDELSLQQADVVLV--LQTESDGWYYGERlrDGERGWFPSSCAK 54

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 37.51 E-value: 2.08e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVI-TVLEQQDMWWFGEVQGQ-KGWFPKSYVK 925
Cdd:cd11969      3 KALYDYRAKRSDELSFCKGALIhNVSKETGGWWKGDYGGKvQHYFPSNYVE 53

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 37.36 E-value: 2.09e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTVGD--KAGVFPSNYV 1013
Cdd:cd11858      2 YKALYDFAGSVANELSLKKDDIVYIVQKEDNgWWLAKKLDesKEGWVPAAYL 53

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 42.26 E-value: 2.12e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  295 EPVLEDEQQQLEKKLPVTFEDKKRENFERGNL----ELEKRRQALLEQQRKEQERLAQL--ERAEQERKERERQeQERKR 368
Cdd:TIGR00618  541 ETSEEDVYHQLTSERKQRASLKEQMQEIQQSFsiltQCDNRSKEDIPNLQNITVRLQDLteKLSEAEDMLACEQ-HALLR 619

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  369 QLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLE-WERNRRQEL------LNQRNKEQEDIVVLKAKKKTL 441
Cdd:TIGR00618  620 KLQPEQDLQDVRLHLQQCSQELALKLTALHALQLTLTQERVREhALSIRVLPKellasrQLALQKMQSEKEQLTYWKEML 699

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  442 EFELEALNDkKHQLEGKL----QDIRCRLTTQRQEI--------ESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQ 509
Cdd:TIGR00618  700 AQCQTLLRE-LETHIEEYdrefNEIENASSSLGSDLaaredalnQSLKELMHQARTVLKARTEAHFNNNEEVTAALQTGA 778

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  510 ILNDQLKQVQQNSLHRDSLVTLKRALEAKelARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELreiHNKQ-QLQKQKSM 588
Cdd:TIGR00618  779 ELSHLAAEIQFFNRLREEDTHLLKTLEAE--IGQEIPSDEDILNLQCETLVQEEEQFLSRLEEK---SATLgEITHQLLK 853

                          330       340
                   ....*....|....*....|....
gi 1061899772  589 EAERLKQKEQ----ERKIIELEKQ 608
Cdd:TIGR00618  854 YEECSKQLAQltqeQAKIIQLSDK 877

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 37.69 E-value: 2.12e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  876 AQALYPWRAKKDNHLNFNKNDVITVL------EQQDMWWFG--EVQGQKGWFPKSYVKLI 927
Cdd:cd11790      5 VRATHDYTAEDTDELTFEKGDVILVIpfddpeEQDEGWLMGvkESTGCRGVFPENFTERI 64

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212708 [Multi-domain] Cd Length: 52 Bit Score: 37.44 E-value: 2.13e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILV-TKKDGDW-WTGTVGDKAGVFPSNYV 1013
Cdd:cd11774      4 ALYDYDKQTEEELSFNEGDTLDVyDDSDSDWiLVGFNGTQFGFVPANYI 52

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212978 Cd Length: 53 Bit Score: 37.19 E-value: 2.16e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQ-DM--WWFGEVQGQKGWFPKSYV 924
Cdd:cd12045      3 QGLWDCTGDQPDELSFKRGDTIYILSKEyNRfgWWVGEMKGTIGLVPKAYI 53

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 37.47 E-value: 2.26e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 927
Cdd:cd11869      1 RAEALFDFTGNSKLELNFKAGDVIFLLSRVNKDWLeGTVRGATGIFPLSFVKII 54

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 42.36 E-value: 2.26e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  510 ILNDQLKQVQQNSLHR---DSLVTLKRALEAKELA---------RQHLRDQLDEVEKetrsklqEIDIFNNQLKELR-EI 576
Cdd:TIGR02169  195 EKRQQLERLRREREKAeryQALLKEKREYEGYELLkekealerqKEAIERQLASLEE-------ELEKLTEEISELEkRL 267

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  577 HNKQQLQKQKSMEAERLKQKEQ---ERKIIELEKQKEEAQR--RAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKR--EE 649
Cdd:TIGR02169  268 EEIEQLLEELNKKIKDLGEEEQlrvKEKIGELEAEIASLERsiAEKERELEDAEERLAKLEAEIDKLLAEIEELEReiEE 347

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1061899772  650 SVKKKDGEEKGKQEAQDKLGRLFHQHQEPAK 680
Cdd:TIGR02169  348 ERKRRDKLTEEYAELKEELEDLRAELEEVDK 378

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 41.67 E-value: 2.28e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  327 ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL-ELEKQLEKqreLERQreeerrkeierREAAKRELE 405
Cdd:COG4942     35 EIAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELaALEAELAE---LEKE-----------IAELRAELE 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  406 RQRQLEWERNRRQellnQRNKEQEDIVVLKAKKKTLEFE-----LEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSR 480
Cdd:COG4942    101 AQKEELAELLRAL----YRLGRQPPLALLLSPEDFLDAVrrlqyLKYLAPARREQAEELRADLAELAALRAELEAERAEL 176

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772  481 ELRIAEIthlqqqlqesQQMLGRLIPEKQILNDQLKQVQQNslhrdsLVTLKRALEAKELARQHLRDQLDEVEKETRSK 559
Cdd:COG4942    177 EALLAEL----------EEERAALEALKAERQKLLARLEKE------LAELAAELAELQQEAEELEALIARLEAEAAAA 239

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 37.29 E-value: 2.34e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGElQARGKKrqiGWFPANYVKL 1093
Cdd:cd11770      4 ALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAE-NSKGNR---GLVPKTYLKV 54

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 37.29 E-value: 2.35e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDV-ILVTKKDGDWW-----TGTVgdkaGVFPSNYVR 1014
Cdd:cd11849      4 ALYDFKSAEPNTLSFSEGETfLLLERSNAHWWlvtnhSGET----GYVPANYVK 53

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 37.29 E-value: 2.37e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWF-GEVQGQKGWFPKSYVK 925
Cdd:cd11849      3 RALYDFKSAEPNTLSFSEGETFLLLERSNAhWWLvTNHSGETGYVPANYVK 53

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 37.31 E-value: 2.38e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772  704 KVVyyrALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEKI 762
Cdd:cd11971      1 KVV---AIYDYSKDKDDELSFMEGAIIYV--IKKNDDGWYEGVCNGVTGLFPGNYVESI 54

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212955 [Multi-domain] Cd Length: 53 Bit Score: 37.13 E-value: 2.41e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKK--DGdWWTGTVGDKAGVFPSNYV 1013
Cdd:cd12022      2 YITIKAYTAVEEDELTLLEGEAIEVIHKllDG-WWVVRKGEVTGYFPSMYL 51

RNase Y N-terminal region;

Pssm-ID: 463456 [Multi-domain] Cd Length: 201 Bit Score: 40.64 E-value: 2.43e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  301 EQQQLEKKLPVTFE--DKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKER-ER-----QEQERKRQL-E 371
Cdd:pfam12072   79 ELQRQERRLLQKEEtlDRKDESLEKKEESLEKKEKELEAQQQQLEEKEEELEELIEEQRQElERisgltSEEAKEILLdE 158


                   ....*..
gi 1061899772  372 LEKQLEK 378
Cdd:pfam12072  159 VEEELRH 165

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 37.30 E-value: 2.50e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1042 SYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELQARgkkrqIGWFPANYVK 1092
Cdd:cd11977      8 NFAARDMRELSLREGDVVRIYSRIGGdqGWWKGETNGR-----IGWFPSTYVE 55

Borrelia P83/100 protein; This family consists of several Borrelia P83/P100 antigen proteins.

Pssm-ID: 114011 [Multi-domain] Cd Length: 489 Bit Score: 41.91 E-value: 2.64e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  504 LIP-EKQILNDQLKQVQQNSLHRDSLVtlKRALEAKELARQHLRDQLD--EVEKETRSKLQEIDIFNNQLKELREIHNKQ 580
Cdd:pfam05262  157 VIPlKKNILSGNVSDVDTDSISDKKVV--EALREDNEKGVNFRRDMTDlkERESQEDAKRAQQLKEELDKKQIDADKAQQ 234

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  581 QLQ-KQKSMEAER--LKQKEQERKIIELEKQKEEAQ--RRAQERDKQWLEHVQQE----DEHQRPRKLHEEEKLKREesv 651
Cdd:pfam05262  235 KADfAQDNADKQRdeVRQKQQEAKNLPKPADTSSPKedKQVAENQKREIEKAQIEikknDEEALKAKDHKAFDLKQE--- 311

                          170
                   ....*....|....*.
gi 1061899772  652 kkkdgEEKGKQEAQDK 667
Cdd:pfam05262  312 -----SKASEKEAEDK 322

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212874 Cd Length: 57 Bit Score: 37.20 E-value: 2.75e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-----WWFGEVQGQKGWFPKSYV 924
Cdd:cd11941      1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDKkgspeWSLVEVNGQRGYVPSSYL 55

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 36.79 E-value: 2.80e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1038 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKrqiGWFPANY 1090
Cdd:cd11845      1 IYVAlyDYEARTDDDLSFKKGDRLQILDDSDGDWWLARHLSTGKE---GYIPSNY 52

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 36.98 E-value: 2.81e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772 1043 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKL 1093
Cdd:cd11828      8 HVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDE-----EGWFPASFVRL 53

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 41.29 E-value: 2.85e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  447 ALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLqqqlqesqqmlgrlipEKQI--LNDQLKQVQQNslh 524
Cdd:COG4942     17 AQADAAAEAEAELEQLQQEIAELEKELAALKKEEKALLKQLAAL----------------ERRIaaLARRIRALEQE--- 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  525 rdsLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIE 604
Cdd:COG4942     78 ---LAALEAELAELEKEIAELRAELEAQKEELAELLRALYRLGRQPPLALLLSPEDFLDAVRRLQYLKYLAPARREQAEE 154

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  605 LEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGR 670
Cdd:COG4942    155 LRADLAELAALRAELEAERAELEALLAELEEERAALEALKAERQKLLARLEKELAELAAELAELQQ 220

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 36.91 E-value: 2.86e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILV-TKKDGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11982      3 FMAVKPYQSQAEGEISLSKGEKIKVlSVGEGGFWEGQVKGRVGWFPSDCV 52

Src Homology 3 domain of Amphiphysin I; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213016 Cd Length: 72 Bit Score: 37.57 E-value: 2.91e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  711 LYPFESRSHDEITIQPGDIVMVDESQTG---EPGWLGG----------ELKGKTGWFPANYAEKI 762
Cdd:cd12140      8 LHDFEAANSDELELKRGDIVLVVPSETAadqDAGWLTGvkesdwlqyrDASAYKGLFPENFTRRL 72

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 37.24 E-value: 2.97e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKDGD--WWTGTV-GDKAGVFPSNYV 1013
Cdd:cd11998      5 ALYDYDGQEQDELSFKAGDELTKLEDEDEqgWCKGRLdSGQVGLYPANYV 54

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 37.32 E-value: 2.98e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKG-----KTGWFPANYAEK 761
Cdd:cd11887      5 KALYPYESDHEDDLNFDVGQLITVTEEEDAD--WYFGEYVDsngntKEGIFPKNFVEV 60

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212702 [Multi-domain] Cd Length: 54 Bit Score: 36.87 E-value: 3.02e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1038 QVIA--SYTATGPEQLTLAPGQ-LILIRKKNPGgWWegelQARGKKRQIGWFPANYVK 1092
Cdd:cd11768      1 IVVAlyDFQPIEPGDLPLEKGEeYVVLDDSNEH-WW----RARDKNGNEGYIPSNYVT 53

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 37.05 E-value: 3.04e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1061899772 1123 DYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd12017      7 EFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKEGWAPSSYI 51

chromosome segregation protein; Provisional

Pssm-ID: 100796 [Multi-domain] Cd Length: 895 Bit Score: 41.81 E-value: 3.15e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  416 RRQELLNQR---NKEQEDIVVLKAKKKTLEFELEALNDKKHQLegklqdircrlttQRQEIESTNKSRELRIAEITHLQq 492
Cdd:PRK01156   150 QRKKILDEIleiNSLERNYDKLKDVIDMLRAEISNIDYLEEKL-------------KSSNLELENIKKQIADDEKSHSI- 215

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  493 qlqesqqmlgrLIPEKQILNDQLKQVQQNSLHRDSlvTLKRALEAKELArqhlrDQLDEVEKETRSKLQEIDIFNNQLKE 572
Cdd:PRK01156   216 -----------TLKEIERLSIEYNNAMDDYNNLKS--ALNELSSLEDMK-----NRYESEIKTAESDLSMELEKNNYYKE 277

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  573 LREIHN--------------------KQQLQKQKSM----EAERLKQKEQERKIIELEK---QKEEAQRRAQERDKQWLE 625
Cdd:PRK01156   278 LEERHMkiindpvyknrnyindyfkyKNDIENKKQIlsniDAEINKYHAIIKKLSVLQKdynDYIKKKSRYDDLNNQILE 357

                          250       260
                   ....*....|....*....|....
gi 1061899772  626 HVQQEDEHQRPRKLHEEEKLKREE 649
Cdd:PRK01156   358 LEGYEMDYNSYLKSIESLKKKIEE 381

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 36.91 E-value: 3.31e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1037 AQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKLL 1094
Cdd:cd11920      3 ARAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGR-----VGIFPISYVEKL 55

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 36.64 E-value: 3.48e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQ---DMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11866      3 MGLWDCSGNEPDELSFKRGDLIYIISKEydsFGWWVGELNGKVGLVPKDYL 53

Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; This subfamily is composed of Rho GTPase-activating proteins including mammalian ARHGAP9, and vertebrate ARHGAPs 12 and 27. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP9 functions as a GAP for Rac and Cdc42, but not for RhoA. It negatively regulates cell migration and adhesion. It also acts as a docking protein for the MAP kinases Erk2 and p38alpha, and may facilitate cross-talk between the Rho GTPase and MAPK pathways to control actin remodeling. ARHGAP27, also called CAMGAP1, shows GAP activity towards Rac1 and Cdc42. It binds the adaptor protein CIN85 and may play a role in clathrin-mediated endocytosis. ARHGAP12 has been shown to display GAP activity towards Rac1. It plays a role in regulating HFG-driven cell growth and invasiveness. ARHGAPs in this subfamily contain SH3, WW, Pleckstin homology (PH), and RhoGAP domains. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212821 [Multi-domain] Cd Length: 54 Bit Score: 36.58 E-value: 3.51e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772 1122 YDYTAQNDDELAFNKGQIINVLNKEDPDWW--KGEVNGQVGLFPSNY 1166
Cdd:cd11888      8 FEYTGKDGRKVSIKEGERFLLLKKSNDDWWqvRRPGDSKPFYVPAQY 54

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212707 [Multi-domain] Cd Length: 57 Bit Score: 36.63 E-value: 3.61e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVI-LVTKKDGDWWT----GTVGD---KAGVFPSNY 1012
Cdd:cd11773      4 ALYDYEPQTEDELTIQEDDILyLLEKSDDDWWKvklkVNSSDddePVGLVPATY 57

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 36.82 E-value: 3.62e-03

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1061899772  978 DLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11921     16 ELTLQKGDIVYIHKEvDKNWLEGEHHGRVGIFPANYVEV 54

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 36.83 E-value: 3.77e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  705 VVYyrALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd11952      2 VVY--ALWDYSAEFPDELSFKEGDMVTVLRKDGEGTDWWWASLCGREGYVPRNY 53

Src Homology 3 domain of Sorting nexin 9; Sorting nexin 9 (SNX9), also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX9 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212831 Cd Length: 57 Bit Score: 36.76 E-value: 3.79e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772 1037 AQVIASYTA-TGPEQLTLAPGQLILIRKKNPGGWWegeLQARGKKRQIGWFPANYVKLL 1094
Cdd:cd11898      2 ARVLYDFAAePGNNELTVKEGEIITVTNPNVGGGW---IEAKNSQGERGLVPTDYVEIV 57

Coiled-coil domain-containing protein 158; CCDC158 is a family of proteins found in eukaryotes. The function is not known.

Pssm-ID: 464943 [Multi-domain] Cd Length: 1112 Bit Score: 41.64 E-value: 3.90e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  295 EPVLEDEQQQ---LEKKLPVTFEDKKRENFergnleleKRRQALLEQQRKEQErlAQLER---AEQERKERERQEqerkr 368
Cdd:pfam15921   77 ERVLEEYSHQvkdLQRRLNESNELHEKQKF--------YLRQSVIDLQTKLQE--MQMERdamADIRRRESQSQE----- 141

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  369 qlELEKQLEKQRelerqreeerrkeierreaakRELERQRQLewernrRQELLNQRNKEQEDIvvlkaKKKTLEFeleal 448
Cdd:pfam15921  142 --DLRNQLQNTV---------------------HELEAAKCL------KEDMLEDSNTQIEQL-----RKMMLSH----- 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  449 ndkkhqlEGKLQDIRCRLT---------TQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPekqiLNDQLKQVQ 519
Cdd:pfam15921  183 -------EGVLQEIRSILVdfeeasgkkIYEHDSMSTMHFRSLGSAISKILRELDTEISYLKGRIFP----VEDQLEALK 251

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  520 QNSLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQ------EIDIFNNQLKELREIHNKQQLQKQKSMEAERL 593
Cdd:pfam15921  252 SESQNKIELLLQQHQDRIEQLISEHEVEITGLTEKASSARSQansiqsQLEIIQEQARNQNSMYMRQLSDLESTVSQLRS 331

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899772  594 KQKEQER----KIIELEKQ----KEEAQRRAQERDKQWLEHVQQEDEHQR-PRKLHEEEK---LKREES 650
Cdd:pfam15921  332 ELREAKRmyedKIEELEKQlvlaNSELTEARTERDQFSQESGNLDDQLQKlLADLHKREKelsLEKEQN 400

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 36.82 E-value: 3.90e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYVKL 1093
Cdd:cd11928      4 KALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCH-----GFLPASYIQC 54

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 41.44 E-value: 3.92e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  508 KQILNDQLKQVQQNSLHRDSLVTLKRALE---------------AKELARqhLRDQLDEVEKeTRSKLQEIDIfnnQLKE 572
Cdd:COG4913    623 EEELAEAEERLEALEAELDALQERREALQrlaeyswdeidvasaEREIAE--LEAELERLDA-SSDDLAALEE---QLEE 696

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  573 LREIHN-----KQQLQKQKSMEAERLKQKEQERKiiELEKQKEEAQRRAQERDKQWLE-HVQQEDEHQRPRKLHE--EEK 644
Cdd:COG4913    697 LEAELEeleeeLDELKGEIGRLEKELEQAEEELD--ELQDRLEAAEDLARLELRALLEeRFAAALGDAVERELREnlEER 774

                          170       180       190
                   ....*....|....*....|....*....|...
gi 1061899772  645 LKREESvkkkdgeekGKQEAQDKLGRLFHQHQE 677
Cdd:COG4913    775 IDALRA---------RLNRAEEELERAMRAFNR 798

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212978 Cd Length: 53 Bit Score: 36.42 E-value: 3.97e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd12045      1 FYQGLWDCTGDQPDELSFKRGDTIYILSKEYNRFGWWVGEMKGTIGLVPKAY 52

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 36.56 E-value: 4.10e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVM----VDESqtgepgWLGGELKGKTGWFPANYAE 760
Cdd:cd11782      3 RAKYNFNADTGVELSFRKGDVITltrrVDEN------WYEGRIGGRQGIFPVSYVQ 52

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 36.51 E-value: 4.15e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVL-EQQDMWWFGEVQGQKGWFPKSYVK 925
Cdd:cd12055      1 RCQVAFSYLPQNEDELELKVGDIIEVVgEVEEGWWEGVLNGKTGMFPSNFIK 52

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 36.68 E-value: 4.17e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVdesqTG--EPGWLGGE--LKGKTGWFPANY 758
Cdd:cd11784      2 CVALHSYSAHRPEELELQKGEGVRV----LGkfQEGWLRGLslVTGRVGIFPSNY 52

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 36.89 E-value: 4.27e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  877 QALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQK--GWFPKSYVK 925
Cdd:cd11917      8 QALYNYMPRNEDELELREGDVIDVMEKCDDGWFvGTSRRTKffGTFPGNYVK 59

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 36.52 E-value: 4.30e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1061899772  712 YPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANY 758
Cdd:cd11902      7 FAYVAEREDELSLVKGSRVTVMEKCSD--GWWRGSYNGQIGWFPSNY 51

Coiled-coil domain-containing protein 66; This protein family, named Coiled-coil domain-containing protein 66 (CCDC) refers to a protein domain found in eukaryotes, and is approximately 160 amino acids in length. CCDC66 protein is detected mainly in the inner segments of photoreceptors in many vertebrates including mice and humans. It has been found in dogs, that a mutation in the CCDC66 gene causes generalized progressive retinal atrophy (gPRA). This shows that the protein encoded for by this gene is vital for healthy vision and guards against photoreceptor cell degeneration. The structure of CCDC66 proteins includes a heptad repeat pattern which contains at least one coiled-coil domain. There are at least two or more alpha-helices which form a cable-like structure.

Pssm-ID: 434558 [Multi-domain] Cd Length: 154 Bit Score: 39.01 E-value: 4.31e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  327 ELEKRRQALLE------QQRKEQERLAQLERaEQERKERERQEQERKRQLELE---------KQLEKQRELERQREEERR 391
Cdd:pfam15236   46 ERERKRQKALEhqnaikKQLEEKERQKKLEE-ERRRQEEQEEEERLRREREEEqkqfeeerrKQKEKEEAMTRKTQALLQ 124

                           90       100
                   ....*....|....*....|....*
gi 1061899772  392 KEIERREAAKRELERQRQLEWERNR 416
Cdd:pfam15236  125 AMQKAQELAQRLKQEQRIRELAEKG 149

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 36.52 E-value: 4.37e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1061899772 1045 ATGPEQLTLAPGQLILIRKKNPGGWWEGELQarGKKRQIGWFPANY 1090
Cdd:cd11821     10 ADNDDELTFSEGEIIVVTGEEDDEWWEGHIE--GDPSRRGVFPVSF 53

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 36.69 E-value: 4.38e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  714 FESRSHDEITIQPGDIVMVdeSQTGEPGWLGGEL--KGKTGWFPANYAE 760
Cdd:cd11940      8 YKAQENDELTLEKADIIMV--RQQSSDGWLEGVRlsDGERGWFPQSHVE 54

putative monovalent cation/H+ antiporter subunit G; Reviewed

Pssm-ID: 183610 Cd Length: 197 Bit Score: 39.67 E-value: 4.63e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  545 LRDQLDEVEKETRSKLQEIDIFNNQLKELReihnkqqlQKQKSMEaERLKQKEQERKIIELEKQKEEAQrraqERDKQWL 624
Cdd:PRK12585   103 IRDQLRSVKKDDIKKKKSLIIRQEQIEKAR--------QEREELE-ERMEWERREEKIDEREDQEEQER----EREEQTI 169

                           90
                   ....*....|
gi 1061899772  625 EHVQQEDEHQ 634
Cdd:PRK12585   170 EEQSDDSEHE 179

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 41.11 E-value: 4.65e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLpvtfedkkrENFERGNLELEKRRQALLEQQRKEQE---RLAQLERAEQERKERERQEQERKRQlELEK 374
Cdd:TIGR00618  533 GEQTYAQLETSE---------EDVYHQLTSERKQRASLKEQMQEIQQsfsILTQCDNRSKEDIPNLQNITVRLQD-LTEK 602

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  375 QLEKQRELERQREeerrkeierreaakrelERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEfELEALNDKKHQ 454
Cdd:TIGR00618  603 LSEAEDMLACEQH-----------------ALLRKLQPEQDLQDVRLHLQQCSQELALKLTALHALQL-TLTQERVREHA 664

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  455 LEGKLQDIRCRLTTQRQEIESTNKSRELRiaeithLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHrdslvTLKRA 534
Cdd:TIGR00618  665 LSIRVLPKELLASRQLALQKMQSEKEQLT------YWKEMLAQCQTLLRELETHIEEYDREFNEIENASS-----SLGSD 733

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  535 LEAKELARQHLRDQLDEvEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQR 614
Cdd:TIGR00618  734 LAAREDALNQSLKELMH-QARTVLKARTEAHFNNNEEVTAALQTGAELSHLAAEIQFFNRLREEDTHLLKTLEAEIGQEI 812

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  615 RAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQ 665
Cdd:TIGR00618  813 PSDEDILNLQCETLVQEEEQFLSRLEEKSATLGEITHQLLKYEECSKQLAQ 863

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 36.28 E-value: 4.71e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDESQTgePGWLGGELKGKTGWFPANYAEK 761
Cdd:cd12016      3 YITTQAYKAENEDEIGFETGVVVEVIQKNL--DGWWKIRYQGKEGWAPATYLKK 54

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).

Pssm-ID: 129694 [Multi-domain] Cd Length: 1311 Bit Score: 41.19 E-value: 4.72e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERE--------RQEQERKRQ 369
Cdd:TIGR00606  476 LDQELRKAERELSKAEKNSLTETLKKEVKSLQNEKADLDRKLRKLDQEMEQLNHHTTTRTQMEmltkdkmdKDEQIRKIK 555

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  370 LELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQedivvlkakkKTLEFELEALN 449
Cdd:TIGR00606  556 SRHSDELTSLLGYFPNKKQLEDWLHSKSKEINQTRDRLAKLNKELASLEQNKNHINNEL----------ESKEEQLSSYE 625

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  450 DKKHQLEGKlQDIRCRLTTQRQEIESTNKSRELRIAE-------ITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNS 522
Cdd:TIGR00606  626 DKLFDVCGS-QDEESDLERLKEEIEKSSKQRAMLAGAtavysqfITQLTDENQSCCPVCQRVFQTEAELQEFISDLQSKL 704

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  523 -LHRDSLVTLKRALEAKELARQHL-------RDQLDEVEK---ETRSKLQEIdifNNQLKELREIHNKQQLQKQKSMEAE 591
Cdd:TIGR00606  705 rLAPDKLKSTESELKKKEKRRDEMlglapgrQSIIDLKEKeipELRNKLQKV---NRDIQRLKNDIEEQETLLGTIMPEE 781

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  592 RLKQKEQ------ERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKL--KREESVKKKDGEEKGKQE 663
Cdd:TIGR00606  782 ESAKVCLtdvtimERFQMELKDVERKIAQQAAKLQGSDLDRTVQQVNQEKQEKQHELDTVvsKIELNRKLIQDQQEQIQH 861


                   ....*...
gi 1061899772  664 AQDKLGRL 671
Cdd:TIGR00606  862 LKSKTNEL 869

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 36.26 E-value: 4.72e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKKDGD---WWTGTVGDKAGVFPSNYV 1013
Cdd:cd11866      2 YMGLWDCSGNEPDELSFKRGDLIYIISKEYDsfgWWVGELNGKVGLVPKDYL 53

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 36.23 E-value: 4.75e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 924
Cdd:cd11816      4 ARFDFEGEQEDELSFSEGDVITLKEYvGEEWAKGELNGKIGIFPLNFV 51

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.

Pssm-ID: 432349 [Multi-domain] Cd Length: 1191 Bit Score: 41.36 E-value: 4.86e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  294 EEPVLEDEQQQLEKKLPVTFE--DKKRENFERGNLELEKRRQALLEQQRKE----------QERLAQL--------ERAE 353
Cdd:pfam12128  591 DVPEWAASEEELRERLDKAEEalQSAREKQAAAEEQLVQANGELEKASREEtfartalknaRLDLRRLfdekqsekDKKN 670

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  354 QERKERERQEQERKRQLELE-KQLEKQRELERQREEERrkeierreaaKRELERQRQLEWernrrQELLNQRNKEQEDIV 432
Cdd:pfam12128  671 KALAERKDSANERLNSLEAQlKQLDKKHQAWLEEQKEQ----------KREARTEKQAYW-----QVVEGALDAQLALLK 735

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  433 VLKAKKKT-LEFELEALN-DKKHQLEGKLQD--IRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQEsqqmlgRLIPEK 508
Cdd:pfam12128  736 AAIAARRSgAKAELKALEtWYKRDLASLGVDpdVIAKLKREIRTLERKIERIAVRRQEVLRYFDWYQE------TWLQRR 809

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  509 QILNDQLKQVQQNSlhRDSLVTLKRALEAKELARQHL---RDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQ 585
Cdd:pfam12128  810 PRLATQLSNIERAI--SELQQQLARLIADTKLRRAKLemeRKASEKQQVRLSENLRGLRCEMSKLATLKEDANSEQAQGS 887

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  586 KSmeaERLKQKEQERKIIELEKQKEE----------AQRRAQERDKQWLEHvqQEDEHQRPRKL 639
Cdd:pfam12128  888 IG---ERLAQLEDLKLKRDYLSESVKkyvehfknviADHSGSGLAETWESL--REEDHYQNDKG 946

flagellar export protein FliJ; Members of this family are the FliJ protein found, in nearly every case, in the midst of other flagellar biosynthesis genes in bacgterial genomes. Typically the fliJ gene is found adjacent to the gene for the flagellum-specific ATPase FliI. Sequence scoring in the gray zone between trusted and noise cutoffs include both probable FliJ proteins and components of bacterial type III secretion systems.

Pssm-ID: 131526 [Multi-domain] Cd Length: 141 Bit Score: 38.84 E-value: 4.94e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  513 DQLKQVQQnsLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETR----------------SKLQEIDIFNNQLKELREI 576
Cdd:TIGR02473    2 FRLQKLLD--LREKEEEQAKLELAKAQAEFERLETQLQQLIKYREeyeqqalekvgagtsaLELSNYQRFIRQLDQRIQQ 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  577 HNKQQLQKQKSMEA--ERLKQKEQERKIIEL--EKQKEEAQRRAQERDKQWL-EHVQQ 629
Cdd:TIGR02473   80 QQQELALLQQEVEAkrERLLEARRELKALEKlkEKKQKEYRAEEAKREQKEMdELATQ 137

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]

Pssm-ID: 274303 [Multi-domain] Cd Length: 346 Bit Score: 40.60 E-value: 5.11e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  551 EVEKETRSKLQEIDIFNNQLKELREihNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQE 630
Cdd:TIGR02794   51 QANRIQQQKKPAAKKEQERQKKLEQ--QAEEAEKQRAAEQARQKELEQRAAAEKAAKQAEQAAKQAEEKQKQAEEAKAKQ 128

                           90       100
                   ....*....|....*....|....*.
gi 1061899772  631 -------DEHQRPRKLHEEEKLKREE 649
Cdd:TIGR02794  129 aaeakakAEAEAERKAKEEAAKQAEE 154

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 36.35 E-value: 5.11e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1038 QVIA--SYTATGPEQLTLAPGQLILIRKKNPGGWWEGElqARGKkrqIGWFPANYVK 1092
Cdd:cd11870      1 QVVAlhRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGH--SDGR---VGIFPKCFVV 52

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 40.91 E-value: 5.28e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  508 KQILNDQLKQVQQNslhRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKS 587
Cdd:COG4717     66 PELNLKELKELEEE---LKEAEEKEEEYAELQEELEELEEELEELEAELEELREELEKLEKLLQLLPLYQELEALEAELA 142

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  588 MEAERLKQ-KEQERKIIELEKQKEEAQRRAQERDkqwlehvQQEDEHQRPRKLHEEEKLKR 647
Cdd:COG4717    143 ELPERLEElEERLEELRELEEELEELEAELAELQ-------EELEELLEQLSLATEEELQD 196

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 36.14 E-value: 5.32e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDEsqTGEPGWLGGELKGK---TGWFPANY 758
Cdd:cd11821      3 RALYDCQADNDDELTFSEGEIIVVTG--EEDDEWWEGHIEGDpsrRGVFPVSF 53

Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations. Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, two L27 domains, followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213014 Cd Length: 62 Bit Score: 36.42 E-value: 5.46e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772 1118 VIGMYDYTAQNDD-------ELAFNKGQIINVLNKEDPDWWKGE----VNGQVGLFPS 1164
Cdd:cd12081      2 VRAQFEYDPLKDDlipckqaGIRFRVGDILQIISKDDHNWWQAKlensKNGTAGLIPS 59

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 36.26 E-value: 5.47e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd11866      1 WYMGLWDCSGNEPDELSFKRGDLIYIISKEYDSFGWWVGELNGKVGLVPKDY 52

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212977 Cd Length: 53 Bit Score: 36.37 E-value: 5.50e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANY 758
Cdd:cd12044      1 YYQGLWDCFGDNPDELSFQRGDLIYILSKEYNMYGWWVGELNGIVGIVPKDY 52

recombination and DNA strand exchange inhibitor protein; Reviewed

Pssm-ID: 234750 [Multi-domain] Cd Length: 782 Bit Score: 40.97 E-value: 5.61e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  543 QHLRDQLDEVEKETRSKLQEIDIFNNQLKElreihNKQQLQKQKsmEAERLKQKEQERKIIElEKQKEEAQRRAQERDKQ 622
Cdd:PRK00409   526 EELERELEQKAEEAEALLKEAEKLKEELEE-----KKEKLQEEE--DKLLEEAEKEAQQAIK-EAKKEADEIIKELRQLQ 597

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1061899772  623 WLEHVQQ-----EDEHQR---PRKLHEEEKLKREE 649
Cdd:PRK00409   598 KGGYASVkahelIEARKRlnkANEKKEKKKKKQKE 632

Extracytoplasmic sensor domain CHASE3 (specificity unknown) [Signal transduction mechanisms];

Pssm-ID: 444089 [Multi-domain] Cd Length: 530 Bit Score: 40.66 E-value: 5.72e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  319 ENFERGNLELEKRRQAL---LEQQRKEQERLAQLERAEQERKE------RERQEQERKRQLELEKQLEKQRELERQREEE 389
Cdd:COG5278     79 EPYEEARAEIDELLAELrslTADNPEQQARLDELEALIDQWLAeleqviALRRAGGLEAALALVRSGEGKALMDEIRARL 158

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  390 RRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRcRLTTQ 469
Cdd:COG5278    159 LLLALALAALLLAAAALLLLLLALAALLALAELLLLALARALAALLLLLLLEAELAAAAALLAAAAALAALAAL-ELLAA 237

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  470 RQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDSLVTLKRALEAKELARQHLRDQL 549
Cdd:COG5278    238 LALALALLLAALLLALLAALALAALLAAALLALAALLLALAAAAALAAAAALELAAAEALALAELELELLLAAAAAAAAA 317

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  550 DEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQ 629
Cdd:COG5278    318 AAAAAAALAALLALALATALAAAAAALALLAALLAEAAAAAAEEAEAAAEAAAAALAGLAEVEAEGAAEAVELEVLAIAA 397

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  630 EDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRLFHQHQEPAKPAVQAPWSTAEKGPLTISAQENV 703
Cdd:COG5278    398 AAAAAAAEAAAAAAAAAAASAAEALELAEALAEALALAEEEALALAAASSELAEAGAALALAAAEALAEELAAV 471

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 36.15 E-value: 5.90e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 927
Cdd:cd11971      4 AIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYeGVCNGVTGLFPGNYVESI 54

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2; Shank2, also called ProSAP1 (Proline-rich synapse-associated protein 1) or CortBP1 (Cortactin-binding protein 1), is found in neurons, glia, endocrine cells, liver, and kidney. It plays a role in regulating dendritic spine volume and branching and postsynaptic clustering. Mutations in the Shank2 gene are associated with autism spectrum disorder and mental retardation. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212916 Cd Length: 52 Bit Score: 36.06 E-value: 6.17e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772 1039 VIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGelQARGkkrQIGWFPANYV 1091
Cdd:cd11983      5 VVKSYQPQVEGEIPLHKGDRVKVLSIGEGGFWEG--SARG---HVGWFPAECV 52

Src Homology 3 domain of Disks large homolog proteins; The DLG-like proteins are scaffolding proteins that cluster at synapses and are also called PSD (postsynaptic density)-95 proteins or SAPs (synapse-associated proteins). They play important roles in synaptic development and plasticity, cell polarity, migration and proliferation. They are members of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG-like proteins contain three PDZ domains and varying N-terminal regions. All DLG proteins exist as alternatively-spliced isoforms. Vertebrates contain four DLG proteins from different genes, called DLG1-4. DLG4 and DLG2 are found predominantly at postsynaptic sites and they mediate surface ion channel and receptor clustering. DLG3 is found axons and some presynaptic terminals. DLG1 interacts with AMPA-type glutamate receptors and is critical in their maturation and delivery to synapses. The SH3 domain of DLG4 binds and clusters the kainate subgroup of glutamate receptors via two proline-rich sequences in their C-terminal tail. It also binds AKAP79/150 (A-kinase anchoring protein). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212795 [Multi-domain] Cd Length: 61 Bit Score: 36.15 E-value: 6.17e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772 1121 MYDYTAQNDD-----ELAFNKGQIINVLNKEDPDWWK-------GEvNGQVGLFPS 1164
Cdd:cd11861      5 LFDYDPSRDSglpsqGLSFKFGDILHVTNASDDEWWQarrvtpnGE-EEEVGVIPS 59

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 36.17 E-value: 6.17e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGepgWLGGELKGKTGWFPANY 758
Cdd:cd11990      3 QALCSWTAKKDNHLNFSKNDIITVLEQQEN---WWFGEVHGGRGWFPKSY 49

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 36.41 E-value: 6.25e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKKDGD----WWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd12003      5 ALYDNAAESPEELSFRRGDVLMVLKREHGslpgWWLCSLHGQQGIAPANRLRL 57

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 36.12 E-value: 6.27e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGE--VQGQKGWFPKSYV 924
Cdd:cd12004      4 ALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARslTTKKEGFIPSNYV 52

Src Homology 3 domain of the p85beta regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85beta binds CD28 and may be involved in the activation and differentiation of antigen-stimulated T cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212842 Cd Length: 74 Bit Score: 36.73 E-value: 6.30e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMV-------------DESQTGEPGWLGG--ELKGKTGWFPANYAEKI 762
Cdd:cd11909      3 YRALYPYRKEREEDIDLLPGDVLTVsraalqalgvkegGEQCPQSIGWILGlnERTKQRGDFPGTYVEFL 72

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 36.14 E-value: 6.35e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  708 YRALYPFESRSHDEITIQPGDI-VMVDESQtgEPGWLGGELKGKTGWFPANYAE 760
Cdd:cd11849      2 YRALYDFKSAEPNTLSFSEGETfLLLERSN--AHWWLVTNHSGETGYVPANYVK 53

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 35.92 E-value: 6.37e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  875 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQ---GQKGWFPKSYVKL 926
Cdd:cd11940      1 QVQCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEGVRlsdGERGWFPQSHVEE 55

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 36.08 E-value: 6.39e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVM----VDESqtgepgWLGGELKGKTGWFPANYAE 760
Cdd:cd11927      4 KALYNYEGKEPGDLKFSKGDIIIlrrqVDEN------WYHGEVNGIHGFFPTNFVQ 53

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212858 Cd Length: 57 Bit Score: 36.13 E-value: 6.48e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  965 FIAMYTYESSEQGDLTFQQGDVILVTKKDGD-WWTGTV--GDKAGVFPSNYV 1013
Cdd:cd11925      3 YLALYAYKPQKNDELELRKGEMYRVIEKCQDgWFKGTSlrTGVSGVFPGNYV 54

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 36.17 E-value: 6.58e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQT-GEPGWLGGELKGKTGWFPAN 757
Cdd:cd11844      3 RALYDNVAESPDELAFRRGDILTVLEQNTaGLEGWWLCSLRGRQGIAPGN 52

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 36.14 E-value: 6.68e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQ--GQKGWFPKSYVKL 926
Cdd:cd11789      4 AMYDYAAADDDEVSFQEGDVIINVEIIDDgWMEGTVQrtGQSGMLPANYVEL 55

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 40.52 E-value: 6.88e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  258 LPPVLPPEYIPPSFRRVRSGSGISVISSTSVDQRLPEEpvLEDEQQQLEKKLPVTFEDKKRENFERGN--LELEKRRQAL 335
Cdd:COG4717    330 LPPDLSPEELLELLDRIEELQELLREAEELEEELQLEE--LEQEIAALLAEAGVEDEEELRAALEQAEeyQELKEELEEL 407

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  336 LEQ-QRKEQERLAQLERAEQERKERERQEQERKRQlELEKQLEKQRELERQREeerrkeierreAAKRELERQRQLEWER 414
Cdd:COG4717    408 EEQlEELLGELEELLEALDEEELEEELEELEEELE-ELEEELEELREELAELE-----------AELEQLEEDGELAELL 475

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  415 NRRQELLNQRNKEQEDIVVLKAKKKTLEFELEAL-NDKKHQLEGKLQDIRCRLT 467
Cdd:COG4717    476 QELEELKAELRELAEEWAALKLALELLEEAREEYrEERLPPVLERASEYFSRLT 529

Glutamine-rich N-terminal helical domain of HDAC9, a Class IIa histone deacetylase; This family consists of the glutamine-rich domain of histone deacetylase 9 (HDAC9). It belongs to a superfamily that consists of the glutamine-rich N-terminal helical extension to certain Class IIa histone deacetylases (HDACs), including HDAC4, HDAC5 and HDCA9; it is missing from HDAC7. This domain confers responsiveness to calcium signals and mediates interactions with transcription factors and cofactors, and it is able to repress transcription independently of the HDAC C-terminal, zinc-dependent catalytic domain. It has many intra- and inter-helical interactions which are possibly involved in reversible assembly and disassembly of proteins. HDACs regulate diverse cellular processes through enzymatic deacetylation of histone as well as non-histone proteins, in particular deacetylating N(6)-acetyl-lysine residues.

Pssm-ID: 197399 [Multi-domain] Cd Length: 90 Bit Score: 37.04 E-value: 7.03e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  289 DQRLPEEPVLEDEQQQLEKKLPVTFEDKKRENFER---GNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQE 365
Cdd:cd10163      6 EKQLQQELLLIQQQQQIQKQLLIAEFQKQHENLTRqhqAQLQEHLKLQQELLAMKQQQELLEKEQKLEQQRQEQELERHR 85


                   ....*
gi 1061899772  366 RKRQL 370
Cdd:cd10163     86 REQQL 90

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.

Pssm-ID: 432349 [Multi-domain] Cd Length: 1191 Bit Score: 40.59 E-value: 7.05e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  446 EALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQilNDQLKQVQQNSLHR 525
Cdd:pfam12128  600 EELRERLDKAEEALQSAREKQAAAEEQLVQANGELEKASREETFARTALKNARLDLRRLFDEKQ--SEKDKKNKALAERK 677

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  526 DSLVTLKRALEAK--------ELARQHLRDQLDEVEKETRSKLQE-IDIFNNQLKELreihnKQQLQKQKSMEAERLKQK 596
Cdd:pfam12128  678 DSANERLNSLEAQlkqldkkhQAWLEEQKEQKREARTEKQAYWQVvEGALDAQLALL-----KAAIAARRSGAKAELKAL 752

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  597 EQERK-------------------IIELEKQKEEAQRRAQE--RDKQWLEHVQQEdehQRPRKLHEEEKLKREESvkkkd 655
Cdd:pfam12128  753 ETWYKrdlaslgvdpdviaklkreIRTLERKIERIAVRRQEvlRYFDWYQETWLQ---RRPRLATQLSNIERAIS----- 824

                          250
                   ....*....|....*.
gi 1061899772  656 geekgkqEAQDKLGRL 671
Cdd:pfam12128  825 -------ELQQQLARL 833

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 36.10 E-value: 7.08e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKLL 1094
Cdd:cd12054      4 KVLFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGK-----SGLFPSNFVKEL 55

Outer membrane protein (OmpH-like); This family includes outer membrane proteins such as OmpH among others. Skp (OmpH) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.

Pssm-ID: 214922 [Multi-domain] Cd Length: 140 Bit Score: 38.33 E-value: 7.15e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772   298 LEDEQQQLEKKLpvtfeDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLE 377
Cdd:smart00935   23 LEKEFKKRQAEL-----EKLEKELQKLKEKLQKDAATLSEAAREKKEKELQKKVQEFQRKQQKLQQDLQKRQQEELQKIL 97


                    ..
gi 1061899772   378 KQ 379
Cdd:smart00935   98 DK 99

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 40.52 E-value: 7.18e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  372 LEKQLEKQRElerqreEERRKEIERREAAKRELERQRQlewernrrqeLLNQRNKEQEDIVVLKAKKKTLEFELEALNDK 451
Cdd:COG4717     47 LLERLEKEAD------ELFKPQGRKPELNLKELKELEE----------ELKEAEEKEEEYAELQEELEELEEELEELEAE 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  452 KHQLEGKLQDIRCRLTTQRQEIESTNKSRELriaeithlqqqlqesqqmlgrlipekQILNDQLKQVQQnslHRDSLVTL 531
Cdd:COG4717    111 LEELREELEKLEKLLQLLPLYQELEALEAEL--------------------------AELPERLEELEE---RLEELREL 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  532 KRALEAKELARQHLRDQLDEVEKETR-SKLQEIDIFNNQLKELREihNKQQLQKQKSMEAERLKQKEQERKIIELEKQKE 610
Cdd:COG4717    162 EEELEELEAELAELQEELEELLEQLSlATEEELQDLAEELEELQQ--RLAELEEELEEAQEELEELEEELEQLENELEAA 239


                   ....*...
gi 1061899772  611 EAQRRAQE 618
Cdd:COG4717    240 ALEERLKE 247

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 36.00 E-value: 7.21e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1061899772  711 LYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANY 758
Cdd:cd11815      5 LHDFPAEHSDDLSLNSGEIVYLLEKIDTE--WYRGKCKNTTGIFPANH 50

Src homology 3 domain of DBL's Big Sister (DBS), a guanine nucleotide exchange factor; DBS, also called MCF2L (MCF2-transforming sequence-like protein) or OST, is a Rho GTPase guanine nucleotide exchange factor (RhoGEF), facilitating the exchange of GDP and GTP. It was originally isolated from a cDNA screen for sequences that cause malignant growth. It plays roles in regulating clathrin-mediated endocytosis and cell migration through its activation of Rac1 and Cdc42. Depending on cell type, DBS can also activate RhoA and RhoG. DBS contains a Sec14-like domain, spectrin-like repeats, a RhoGEF [or Dbl homology (DH)] domain, a Pleckstrin homology (PH) domain, and an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212791 Cd Length: 55 Bit Score: 35.73 E-value: 7.31e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVdESQTGEPGWLGGEL-KGKTGWFPAN 757
Cdd:cd11857      2 YTVVADYEKGGPDDLTVKSGDLVQL-IHEGDEGQWLVKNLsTRKEGWVPAA 51

Src homology 3 domain of JNK-interacting proteins 1 and 2, and similar domains; JNK-interacting proteins (JIPs) function as scaffolding proteins for c-Jun N-terminal kinase (JNK) signaling pathways. They bind to components of Mitogen-activated protein kinase (MAPK) pathways such as JNK, MKK, and several MAP3Ks such as MLK and DLK. There are four JIPs (JIP1-4); all contain a JNK binding domain. JIP1 and JIP2 also contain SH3 and Phosphotyrosine-binding (PTB) domains. Both are highly expressed in the brain and pancreatic beta-cells. JIP1 functions as an adaptor linking motor to cargo during axonal transport and also is involved in regulating insulin secretion. JIP2 form complexes with fibroblast growth factor homologous factors (FHFs), which facilitates activation of the p38delta MAPK. The SH3 domain of JIP1 homodimerizes at the interface usually involved in proline-rich ligand recognition, despite the lack of this motif in the domain itself. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212735 Cd Length: 55 Bit Score: 35.75 E-value: 7.33e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIVMVDesQTGEPGWLGG-ELK-GKTGWFPANYA 759
Cdd:cd11801      2 HRALHKFIPRHEDEIELDIGDPVYVE--QEADDLWCEGtNLRtGQRGIFPAAYV 53

Calcium binding and coiled-coil domain (CALCOCO1) like; Proteins found in this family are similar to the coiled-coil transcriptional coactivator protein coexpressed by Mus musculus (CoCoA/CALCOCO1). This protein binds to a highly conserved N-terminal domain of p160 coactivators, such as GRIP1, and thus enhances transcriptional activation by a number of nuclear receptors. CALCOCO1 has a central coiled-coil region with three leucine zipper motifs, which is required for its interaction with GRIP1 and may regulate the autonomous transcriptional activation activity of the C-terminal region.

Pssm-ID: 462303 [Multi-domain] Cd Length: 488 Bit Score: 40.26 E-value: 7.36e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  298 LEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRqalLEQQRKEQERlaQLERAEQE-RKERERQEQERKRQleleKQL 376
Cdd:pfam07888   36 LEECLQERAELLQAQEAANRQREKEKERYKRDREQ---WERQRRELES--RVAELKEElRQSREKHEELEEKY----KEL 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  377 EKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEDIVVlkAKKKTLEFELEALNDKKHQLE 456
Cdd:pfam07888  107 SASSEELSEEKDALLAQRAAHEARIRELEEDIKTLTQRVLERETELERMKERAKKAG--AQRKEEEAERKQLQAKLQQTE 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  457 GKLqdirCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQ--NSLHRdSLVTLKRA 534
Cdd:pfam07888  185 EEL----RSLSKEFQELRNSLAQRDTQVLQLQDTITTLTQKLTTAHRKEAENEALLEELRSLQErlNASER-KVEGLGEE 259

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  535 LEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEK--QKEEA 612
Cdd:pfam07888  260 LSSMAAQRDRTQAELHQARLQAAQLTLQLADASLALREGRARWAQERETLQQSAEADKDRIEKLSAELQRLEErlQEERM 339

                          330
                   ....*....|....
gi 1061899772  613 QRR------AQERD 620
Cdd:pfam07888  340 EREklevelGREKD 353

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212709 [Multi-domain] Cd Length: 57 Bit Score: 35.76 E-value: 7.44e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDV--ILVTKKDGDWW------TGtvgdKAGVFPSNYVRL 1015
Cdd:cd11775      4 KVLYDFDAQSDDELTVKEGDVvyILDDKKSKDWWmvenvsTG----KEGVVPASYIEI 57

Apg6 coiled-coil region; In yeast, 15 Apg proteins coordinate the formation of autophagosomes. Autophagy is a bulk degradation process induced by starvation in eukaryotic cells. Apg6/Vps30p has two distinct functions in the autophagic process, either associated with the membrane or in a retrieval step of the carboxypeptidase Y sorting pathway.

Pssm-ID: 465452 [Multi-domain] Cd Length: 127 Bit Score: 37.96 E-value: 7.56e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  539 ELARQHLRDQLDEVEKetrsklqEIDIFNNQLKELREIHNKQQLQKQKsmEAERLKQKEQE--RKIIELEKQKE--EAQR 614
Cdd:pfam17675    8 DLLLEELDKQLEDAEK-------ERDAYISFLKKLEKETPEELEELEK--ELEKLEKEEEEllQELEELEKEREelDAEL 78

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1061899772  615 RAQERDKQWLEhvQQEDEHQRPRKLHEEEKLKREE 649
Cdd:pfam17675   79 EALEEELEALD--EEEEEFWREYNALQLQLLEFQD 111

Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called Dock180, and Dock5 are class A DOCKs and are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock1 binds to DHR-2 in an autoinhibitory manner; binding of Elmo to the SH3 domain of Dock1 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212984 [Multi-domain] Cd Length: 56 Bit Score: 35.95 E-value: 7.58e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772  707 YYRALYPFESRSHDEITIQPGDIVMVDESQTgepGWLGG---ELKGKTGWFPANY 758
Cdd:cd12051      1 YGVAIYNYDARGPDELSLQIGDTVHILETYE---GWYRGytlRKKSKKGIFPASY 52

recombination and DNA strand exchange inhibitor protein; Reviewed

Pssm-ID: 234750 [Multi-domain] Cd Length: 782 Bit Score: 40.58 E-value: 7.75e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  336 LEQQRKEQErlAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAK--RELERQRQLEWE 413
Cdd:PRK00409   525 LEELERELE--QKAEEAEALLKEAEKLKEELEEKKEKLQEEEDKLLEEAEKEAQQAIKEAKKEADEiiKELRQLQKGGYA 602

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1061899772  414 RNRRQEL------LNQRNKEQEDIVVlKAKKKTLEFEL 445
Cdd:PRK00409   603 SVKAHELiearkrLNKANEKKEKKKK-KQKEKQEELKV 639

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 35.74 E-value: 7.90e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1038 QVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrQIGWFPANYVK 1092
Cdd:cd11780      3 RALYSYTPQNEDELELREGDIVYVMEKCDDGWFVGTSERTG---LFGTFPGNYVA 54

ATP-dependent Clp protease, ATP-binding subunit ClpA [Posttranslational modification, protein turnover, chaperones];

Pssm-ID: 440308 [Multi-domain] Cd Length: 836 Bit Score: 40.45 E-value: 7.98e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  528 LVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEidifnnQLKELRE----IHNKQQLQKQKSMEAERLKQK--EQERK 601
Cdd:COG0542    413 LDELERRLEQLEIEKEALKKEQDEASFERLAELRD------ELAELEEeleaLKARWEAEKELIEEIQELKEEleQRYGK 486

                           90       100       110
                   ....*....|....*....|....*....|
gi 1061899772  602 IIELEKQKEEAQRRAQERDKQWLEHVQQED 631
Cdd:COG0542    487 IPELEKELAELEEELAELAPLLREEVTEED 516

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 35.90 E-value: 8.05e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1061899772 1050 QLTLAPGQLILIRKKNPGGWWEGELQargkkRQIGWFPANYVK 1092
Cdd:cd11820     16 ELTFKAGEIITVLDDSDPNWWKGSNH-----RGEGLFPANFVT 53

Second Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212863 Cd Length: 55 Bit Score: 35.74 E-value: 8.07e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1061899772  967 AMYTYE----SSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYV 1013
Cdd:cd11930      4 ALYDFEvkdkEADKDCLPFAKDDILTVIRRvDENWAEGMLGDKIGIFPISYV 55

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 36.12 E-value: 8.50e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899772  708 YRALYPFESRSHDEITIQPGDIvmVDESQTGEPGWLGGELKGKT--GWFPANYAEKI 762
Cdd:cd11917      7 FQALYNYMPRNEDELELREGDV--IDVMEKCDDGWFVGTSRRTKffGTFPGNYVKRL 61

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 35.51 E-value: 8.57e-03

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1061899772  890 LNFNKNDVITVLEQQ-DMWWFGEVQGQKGWFPKSYV 924
Cdd:cd12017     16 ISFQKGQKVEVIDKNpSGWWYVKIDGKEGWAPSSYI 51

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

Pssm-ID: 293879 [Multi-domain] Cd Length: 291 Bit Score: 39.48 E-value: 8.70e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  579 KQQLQKQKSMEAERLK--QKEQERKI-----IELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPR-------KLHEEEK 644
Cdd:cd16269    191 QALTEKEKEIEAERAKaeAAEQERKLleeqqRELEQKLEDQERSYEEHLRQLKEKMEEERENLLKEqeralesKLKEQEA 270


                   ....*
gi 1061899772  645 LKREE 649
Cdd:cd16269    271 LLEEG 275

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 35.57 E-value: 8.83e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1061899772  878 ALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGE--VQGQKGWFPKSYV 924
Cdd:cd12005      4 ALYSYEPSHDGDLGFEKGEKLRILEQSGEWWKAQslTTGQEGFIPFNFV 52

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212844 [Multi-domain] Cd Length: 55 Bit Score: 35.70 E-value: 8.98e-03

                           10        20        30
                   ....*....|....*....|....*....|....
gi 1061899772  709 RALYPFESRSHDEITIQPGDIVMVDESQTGEpGW 742
Cdd:cd11911      3 TALYDFDGTSEGTLSMEEGEILLVLEEDGGD-GW 35

Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called Dock180, and Dock5 are class A DOCKs and are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock1 binds to DHR-2 in an autoinhibitory manner; binding of Elmo to the SH3 domain of Dock1 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212984 [Multi-domain] Cd Length: 56 Bit Score: 35.56 E-value: 9.14e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  966 IAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTGTV---GDKAGVFPSNYVRLK 1016
Cdd:cd12051      3 VAIYNYDARGPDELSLQIGDTVHILETYEGWYRGYTlrkKSKKGIFPASYIHLK 56

Second Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212863 Cd Length: 55 Bit Score: 35.74 E-value: 9.17e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1061899772 1117 QVIGMYDYTAQND----DELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYV 1167
Cdd:cd11930      1 QCKALYDFEVKDKeadkDCLPFAKDDILTVIRRVDENWAEGMLGDKIGIFPISYV 55

Ciliary protein causing Leber congenital amaurosis disease; Lebercilin is a family of eukaryotic ciliary proteins. Mutations in the gene, LCA5, are implicated in the disease Leber congenital amaurosis. In photoreceptors, lebercilin is uniquely localized at the cilium that bridges the inner and outer segments. Lebercilin functions as an integral element of selective protein transport through photoreceptor cilia. Lebercilin specifically interacts with the intraflagellar transport (IFT), and disruption of IFT can lead to Leber congenital amaurosis.

Pssm-ID: 464776 [Multi-domain] Cd Length: 193 Bit Score: 38.73 E-value: 9.52e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  316 KKRENFERGNLELEKRRQALLeqqrKEQERLAQLERAEQERKERERQEQERKRQlELEKQLEKQRElerqreeerrkeie 395
Cdd:pfam15619   78 RLQEKERDLERKLKEKEAELL----RLRDQLKRLEKLSEDKNLAEREELQKKLE-QLEAKLEDKDE-------------- 138

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061899772  396 rreaAKRELERQRQLEwERNRRQELLNQRNKEQEdivvLKAKKKTLEFELEALNDKKHQLEGKL 459
Cdd:pfam15619  139 ----KIQDLERKLELE-NKSFRRQLAAEKKKHKE----AQEEVKILQEEIERLQQKLKEKEREL 193

ribonuclease Y;

Pssm-ID: 178867 [Multi-domain] Cd Length: 535 Bit Score: 39.85 E-value: 9.56e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  521 NSLHRDSLVTLKRAL-EAKELARQHLrdqlDEVEKETRSKLQEIDIFNNQLKEL--------REIHNKQQL--QKQKSME 589
Cdd:PRK00106    60 KTAKRESKALKKELLlEAKEEARKYR----EEIEQEFKSERQELKQIESRLTERatsldrkdENLSSKEKTleSKEQSLT 135

                           90       100
                   ....*....|....*....|....*.
gi 1061899772  590 AERLKQKEQERKIIELEKQKEEAQRR 615
Cdd:PRK00106   136 DKSKHIDEREEQVEKLEEQKKAELER 161

Coiled-coil domain-containing protein 66; This protein family, named Coiled-coil domain-containing protein 66 (CCDC) refers to a protein domain found in eukaryotes, and is approximately 160 amino acids in length. CCDC66 protein is detected mainly in the inner segments of photoreceptors in many vertebrates including mice and humans. It has been found in dogs, that a mutation in the CCDC66 gene causes generalized progressive retinal atrophy (gPRA). This shows that the protein encoded for by this gene is vital for healthy vision and guards against photoreceptor cell degeneration. The structure of CCDC66 proteins includes a heptad repeat pattern which contains at least one coiled-coil domain. There are at least two or more alpha-helices which form a cable-like structure.

Pssm-ID: 434558 [Multi-domain] Cd Length: 154 Bit Score: 38.24 E-value: 9.61e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  548 QLDEVEKETRSKLQEIDIFNNQLKELREIH--NKQQLQKQKSMEAERL-KQKEQERKIIELE----KQKEEAQRRAQERD 620
Cdd:pfam15236   43 QLEERERKRQKALEHQNAIKKQLEEKERQKklEEERRRQEEQEEEERLrREREEEQKQFEEErrkqKEKEEAMTRKTQAL 122

                           90       100
                   ....*....|....*....|....*.
gi 1061899772  621 KQWLEHVQQ--EDEHQRPRKLHEEEK 644
Cdd:pfam15236  123 LQAMQKAQElaQRLKQEQRIRELAEK 148

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 38.10 E-value: 9.68e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899772  314 EDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERqrEEERRKE 393
Cdd:pfam05672   31 EQERLEKEEEERLRKEELRRRAEEERARREEEARRLEEERRREEEERQRKAEEEAEEREQREQEEQERLQK--QKEEAEA 108

                           90       100
                   ....*....|....*....|....*.
gi 1061899772  394 IERREAAKRELERQRQLEWERNRRQE 419
Cdd:pfam05672  109 KAREEAERQRQEREKIMQQEEQERLE 134

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 35.71 E-value: 9.73e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1061899772  967 AMYTYESSEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKAGVFPSNYVRL 1015
Cdd:cd11919      5 AKFDFKAQTLKELPLQKGDIVYIYKQiDQNWYEGEHHGRVGIFPRSYIEL 54