NCBI Conserved Domain Search

The phosphoinositide binding Phox Homology domain of Five SH protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Five SH (FISH), also called Tks5, 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. FISH contains an N-terminal PX domain and five Src homology 3 (SH3) domains. FISH 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. This subfamily also includes proteins with a different number of SH3 domains than FISH, such as Tks4, which contains four SH3 domains instead of five. The Tks4 adaptor protein is required for the formation of functional podosomes. It has overlapping, but not identical, functions as FISH. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

Pssm-ID: 132798 Cd Length: 119 Bit Score: 250.42 E-value: 1.05e-77

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    6 VLDVKVVDVEKRRHPSKHYVYLINVTYSDSTSHIIYRRYSKFFDLQMQLLDKFPIEGGQKDPKKRIIPFLPGKILFRRSH 85
Cdd:cd06888      1 VKDVKVIDVEKRRAPSKHYVYIINVTWSDGSSNVIYRRYSKFFDLQMQLLDKFPIEGGQKDPSQRIIPFLPGKILFRRSH 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2551499755   86 VRDVAMKRLRFIDDYCRALVRLPPQISQSEEVLRFFETK 124
Cdd:cd06888     81 IRDVAVKRLKPIDEYCKALVRLPPHISQCDEVLRFFEAK 119

Fifth (C-terminal) 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 fifth (C-terminal) 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: 212953 Cd Length: 57 Bit Score: 135.09 E-value: 1.01e-37

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2551499755 1059 VYVSIADYRGDEETMGFPEGTSLEVLEKNPNGWWYCQVLDGLQGRKGWVPSNYLERK 1115
Cdd:cd12020      1 VYVSIADYEGDEETAGFQEGVSMEVLEKNPNGWWYCQILDGVKPFKGWVPSNYLEKK 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: 131.31 E-value: 2.05e-36

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  252 EKYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd12077      1 EKYVTVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 54

First 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 first 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: 213007 [Multi-domain] Cd Length: 53 Bit Score: 125.59 E-value: 1.94e-34

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLDA 205
Cdd:cd12074      1 QYVVVSNYEKQENSEISLQAGEVVDVIEKNESGWWFVSTAEEQGWVPATYLES 53

Third 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 third 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: 213012 Cd Length: 54 Bit Score: 119.77 E-value: 2.23e-32

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd12079      2 EYYTIAEFQSCISDGISFRGGQKAEVIEKNSGGWWYVQIGEKEGWAPSSYIDK 54

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: 113.71 E-value: 2.62e-30

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  252 EKYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd12016      1 EKYITTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGKEGWAPATYLKK 54

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: 109.43 E-value: 8.10e-29

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLDA 205
Cdd:cd12015      1 QYVVVADYKKQQPNEISLRAGDVVDVIEKNENGWWFVSLEDEQGWVPATYLEP 53

The phosphoinositide binding Phox Homology domain of the p47phox subunit of NADPH oxidase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p47phox 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 PX domain, two Src Homology 3 (SH3) domains, and a C-terminal domain that contains PxxP motifs for binding SH3 domains. The PX domain of p47phox is unique in that it contains two distinct basic pockets on the membrane-binding surface: one preferentially binds phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and is analogous to the PI3P-binding pocket of p40phox, while the other binds anionic phospholipids such as phosphatidic acid or phosphatidylserine. Simultaneous binding in the two pockets results in increased membrane affinity. The PX domain of p47phox is also involved in protein-protein interaction.

Pssm-ID: 132797 Cd Length: 118 Bit Score: 111.47 E-value: 1.20e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    9 VKVVDVEKRRHPSKHYVYLINVTYSDSTSHIIYRRYSKFFDLQMQLLDKFPIEGGQKDPKKRIIPFLPGKILFRRshvRD 88
Cdd:cd06887      4 IALLGFEKRFVPSQHYVYMFLVKWQDLSEKLVYRRFTEIYEFHKTLKEMFPIEAGDINKENRIIPHLPAPKWFDG---QR 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2551499755   89 VAMKRLRFIDDYCRALVRLPPQISQSEEVLRFFETKPD 126
Cdd:cd06887     81 AAENRQGTLTEYCSTLLSLPPKISRCPHVLDFFKVRPD 118

Fourth 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 fourth 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: 212952 Cd Length: 53 Bit Score: 108.91 E-value: 1.33e-28

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  813 LYRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLEP 865
Cdd:cd12019      1 SYMTTSAYQKVQDSEISFPAGVEVEVLEKQESGWWYVRFGELEGWAPSHYLEL 53

First 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 first 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: 213008 Cd Length: 55 Bit Score: 109.01 E-value: 1.45e-28

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  152 EQYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLDAQ 206
Cdd:cd12075      1 DQYVVVANYQKQESSEISLYVGQVVDIIEKNESGWWFVSTADEQGWVPATCLEAQ 55

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: 105.23 E-value: 2.20e-27

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd12017      1 EYFTIGEFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKEGWAPSSYIEK 53

The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox. It 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. The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase. The PX domain of p40phox is also involved in protein-protein interaction.

Pssm-ID: 132792 Cd Length: 123 Bit Score: 106.75 E-value: 6.05e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    7 LDVKVVDVEKRRHPSKHYVYLINVTYSDSTSHIIYRRYSKFFDLQMQLLDKFPIEGGqKDPKKRIIPFLPGKILFRRShv 86
Cdd:cd06882      4 VSATIADIEEKRGFTNYYVFVIEVKTKGGSKYLIYRRYRQFFALQSKLEERFGPEAG-SSAYDCTLPTLPGKIYVGRK-- 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 2551499755   87 RDVAMKRLRFIDDYCRALVRLPPQISQSEEVLRFFETKPDD 127
Cdd:cd06882     81 AEIAERRIPLLNRYMKELLSLPVWVLMDEDVRLFFYQTESD 121

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: 102.80 E-value: 1.88e-26

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  252 EKYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd12076      1 EKYTVIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEGWAPASYLKK 54

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: 95.40 E-value: 7.46e-24

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd11856      1 SYVAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLE 52

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: 93.47 E-value: 3.61e-23

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd11856      1 SYVAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLEP 53

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.

Pssm-ID: 214610 Cd Length: 105 Bit Score: 94.33 E-value: 7.41e-23

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    11 VVDVEKRrHPSKHYVYLINVTYSDSTSHI-IYRRYSKFFDLQMQLLDKFPieggqkdpkKRIIPFLPGKILFRR--SHVR 87
Cdd:smart00312    1 VVEPEKI-GDGKHYYYVIEIETKTGLEEWtVSRRYSDFLELHSKLKKHFP---------RSILPPLPGKKLFGRlnNFSE 70

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 2551499755    88 DVAMKRLRFIDDYCRALVRLPPQISQSEEVLRFFE 122
Cdd:smart00312   71 EFIEKRRRGLEKYLQSLLNHPELINHSEVVLEFLE 105

Third 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 third 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: 213011 Cd Length: 53 Bit Score: 90.91 E-value: 2.56e-22

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd12078      1 EYYTIADFQTTIPDGISFQAGLKVEVIEKNLSGWWYIQIEDKEGWAPATFIDK 53

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

Pssm-ID: 132768 [Multi-domain] Cd Length: 106 Bit Score: 91.27 E-value: 8.50e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    8 DVKVVDVEKRRHPSKHYV-YLINVTYSDSTSHIIYRRYSKFFDLQMQLLDKFPieggqkdpkKRIIPFLPGKILFRRsHV 86
Cdd:cd06093      1 SVSIPDYEKVKDGGKKYVvYIIEVTTQGGEEWTVYRRYSDFEELHEKLKKKFP---------GVILPPLPPKKLFGN-LD 70

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2551499755   87 RDVAMKRLRFIDDYCRALVRLpPQISQSEEVLRFFE 122
Cdd:cd06093     71 PEFIEERRKQLEQYLQSLLNH-PELRNSEELKEFLE 105

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

Pssm-ID: 132793 Cd Length: 109 Bit Score: 86.26 E-value: 4.99e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    8 DVKVVDVEKRRHPSKHYVYLINVTYSDST--SHIiYRRYSKFFDLQMQLLDKFPIEGgqkdpkkriIPFLPGKILFRRSH 85
Cdd:cd06883      1 EVSVFGFQKRYSPEKYYIYVVKVTRENQTepSFV-FRTFEEFQELHNKLSLLFPSLK---------LPSFPARVVLGRSH 70

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2551499755   86 VRDVAMKRLRFIDDYCRALVRLPPQISQSEEVLRFF 121
Cdd:cd06883     71 IKQVAERRKIELNSYLKSLFNASPEVAESDLVYTFF 106

Fourth (C-terminal) 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 fourth (C-terminal) 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: 212951 Cd Length: 56 Bit Score: 81.86 E-value: 3.84e-19

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755 1060 YVSIADYRGDEETMGFPEGTSLEVLEKNPNGWWYCQVLDGLQGRKGWVPSNYLER 1114
Cdd:cd12018      2 YVAVADFEGDEDTSSFKEGTVFEVREKNSSGWWFCKVLSGGPVWEGWIPSNYLRK 56

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: 81.53 E-value: 4.94e-19

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd11856      1 SYVAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLEP 53

The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. 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, a homolog of the p47phox subunit of phagocytic NADPH oxidase, 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. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of NoxO1 preferentially binds phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2], PI5P, and PI4P.

Pssm-ID: 132799 Cd Length: 121 Bit Score: 83.98 E-value: 5.48e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    4 RTVLDVKVVDVEKRRhpsKHYVYLINVTYSDSTSHIIYRRYSKFFDLQMQLLDKFPIEGGQKDPKKRIIPFLPGKIL--- 80
Cdd:cd06889      3 RHPVDVQGVGVMQKR---RHKTYMFSVLWSDGSELFVYRSLEEFRKLHKQLKEKFPVEAGLLRSSDRVLPKFKDAPSlgs 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2551499755   81 FRRSHVRDVAmkRLRFIDDYCRALVRLPPQISQSEEVLRFFETK 124
Cdd:cd06889     80 LKGSTSRSLA--RLKLLETYCQELLRLDEKVSRSPEVIQFFAPQ 121

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: 79.99 E-value: 2.01e-18

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755 1060 YVSIADYRGDEET-MGFPEGTSLEVLEKNPNGWWYCQVLDglqgRKGWVPSNYLER 1114
Cdd:cd11856      2 YVAIADYEAQGDDeISLQEGEVVEVLEKNDSGWWYVRKGD----KEGWVPASYLEP 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: 79.22 E-value: 2.91e-18

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLEP 865
Cdd:cd11856      2 YVAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLEP 53

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases similar to the Drosophila PI3K_68D protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. PI3K_68D is a novel PI3K which is widely expressed throughout the Drosophila life cycle. In vitro, it has been shown to phosphorylate PI and PI4P. It is involved in signaling pathways that affect pattern formation of Drosophila wings.

Pssm-ID: 132794 Cd Length: 111 Bit Score: 78.61 E-value: 2.44e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    9 VKVVDVEKRRHPSKHYVYLINVT-YSDSTSHIIYRRYSKFFDLQMQLLDKFPIEGgqkdpkkriIPFLPGKILFRRSHVR 87
Cdd:cd06884      4 VTVVGFQKRYDPEKYYVYVVEVTrENQASPQHVFRTYKEFLELYQKLCRKFPLAK---------LHPLSTGSHVGRSNIK 74

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2551499755   88 DVAMKRLRFIDDYCRALVRLPPQISQSEEVLRFF 121
Cdd:cd06884     75 SVAEKRKQDIQQFLNSLFKMAEEVSHSDLVYTFF 108

The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. 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. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of Bem1p specifically binds phosphatidylinositol-4-phosphate (PI4P).

Pssm-ID: 132800 Cd Length: 112 Bit Score: 78.10 E-value: 3.86e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755   24 YVYLINVTYSDSTSHIIYRRYSKFFDLQMQLLDKFPIEGGQKDPkKRIIPFLPGkilfRRSHVRDVAM--KRLRFIDDYC 101
Cdd:cd06890     15 YWYRVRATLSDGKTRYLCRYYQDFYKLHIALLDLFPAEAGRNSS-KRILPYLPG----PVTDVVNDSIslKRLNDLNEYL 89

                           90       100
                   ....*....|....*....|...
gi 2551499755  102 RALVRLPPQISQSEEVLRFFETK 124
Cdd:cd06890     90 NELINLPAYIQTSEVVRDFFANR 112

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: 70.17 E-value: 5.04e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd12017      2 YFTIGEFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKEGWAPSSYIEK 53

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: 69.99 E-value: 5.24e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd12021      2 YRAIADYEKSSKSEMALKTGDVVEVVEKSENGWWFCQLKAKRGWVPASYLE 52

First 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 first 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: 213007 [Multi-domain] Cd Length: 53 Bit Score: 68.20 E-value: 2.65e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd12074      2 YVVVSNYEKQENSEISLQAGEVVDVIEKNESGWWFVSTAEEQGWVPATYLE 52

PX domain; PX domains bind to phosphoinositides.

Pssm-ID: 459940 Cd Length: 84 Bit Score: 68.04 E-value: 6.45e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755   30 VTYSDSTSHIIYRRYSKFFDLQMQLLDKFPIeggqkdpkkRIIPFLPGKILFRRSHVRDVAmKRLRFIDDYCRALVRLPP 109
Cdd:pfam00787    1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPS---------VIIPPLPPKRWLGRYNEEFIE-KRRKGLEQYLQRLLQHPE 70

                           90
                   ....*....|...
gi 2551499755  110 qISQSEEVLRFFE 122
Cdd:pfam00787   71 -LRNSEVLLEFLE 82

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: 65.44 E-value: 2.51e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  813 LYRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLEP 865
Cdd:cd12024      1 LYYATRAYEAQKEDELSVPAGVVVEVLQKSDNGWWLIRYNGRAGYVPSMYLQP 53

Third 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 third 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: 213011 Cd Length: 53 Bit Score: 65.10 E-value: 3.47e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd12078      1 EYYTIADFQTTIPDGISFQAGLKVEVIEKNLSGWWYIQIEDKEGWAPATFIDK 53

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: 64.87 E-value: 4.08e-13

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755   250 REEKYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYL-GKEGWAPASYLK 304
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56

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: 63.98 E-value: 8.59e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLEP 865
Cdd:cd12015      2 YVVVADYKKQQPNEISLRAGDVVDVIEKNENGWWFVSLEDEQGWVPATYLEP 53

Fourth 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 fourth 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: 212952 Cd Length: 53 Bit Score: 63.85 E-value: 9.20e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd12019      2 YMTTSAYQKVQDSEISFPAGVEVEVLEKQESGWWYVRFGELEGWAPSHYLE 52

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: 63.33 E-value: 1.25e-12

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755   152 EQYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVST-AEEQGWVPATYL 203
Cdd:smart00326    3 PQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLgRGKEGLFPSNYV 55

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: 63.21 E-value: 1.60e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd12015      1 QYVVVADYKKQQPNEISLRAGDVVDVIEKNENGWWFVSLEDEQGWVPATYLEP 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: 62.86 E-value: 1.96e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd12017      1 EYFTIGEFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKEGWAPSSYIE 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: 62.74 E-value: 2.32e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd12024      2 YYATRAYEAQKEDELSVPAGVVVEVLQKSDNGWWLIRYNGRAGYVPSMYLQ 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: 62.36 E-value: 3.12e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  152 EQYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd12077      1 EKYVTVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYL 52

First 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 first 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: 213007 [Multi-domain] Cd Length: 53 Bit Score: 62.04 E-value: 4.05e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYL 303
Cdd:cd12074      1 QYVVVSNYEKQENSEISLQAGEVVDVIEKNESGWWFVSTAEEQGWVPATYL 51

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: 61.70 E-value: 5.16e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755 1060 YVSIADYR-GDEETMGFPEGTSLEVLEKNPNGWWYCQVldglQGRKGWVPSNYLER 1114
Cdd:cd12017      2 YFTIGEFQaTIQDGISFQKGQKVEVIDKNPSGWWYVKI----DGKEGWAPSSYIEK 53

The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

Pssm-ID: 132822 Cd Length: 109 Bit Score: 63.41 E-value: 5.37e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    8 DVKVVDVEKRRHPSKHYVYLINVTYS-DSTSHIIYRRYSKFFDLQMQLLDKFPIEGgqkdpkkriIPFLPGKILFRRSHV 86
Cdd:cd07289      1 EVSVFTYHKRYNPDKHYIYVVRILREgQIEPSFVFRTFDEFQELHNKLSILFPLWK---------LPGFPNKMVLGRTHI 71

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2551499755   87 RDVAMKRLRFIDDYCRALVRLPPQISQSEEVLRFF 121
Cdd:cd07289     72 KDVAAKRKVELNSYIQSLMNSSTEVAECDLVYTFF 106

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: 61.32 E-value: 6.61e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  152 EQYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd12016      1 EKYITTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGKEGWAPATYL 52

First 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 first 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: 213007 [Multi-domain] Cd Length: 53 Bit Score: 60.50 E-value: 1.50e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYID 503
Cdd:cd12074      1 QYVVVSNYEKQENSEISLQAGEVVDVIEKNESGWWFVSTAEEQGWVPATYLE 52

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: 59.78 E-value: 1.83e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQ-GWVPATY 202
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNGGReGLFPANY 51

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: 59.74 E-value: 2.24e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd12015      1 QYVVVADYKKQQPNEISLRAGDVVDVIEKNENGWWFVSLEDEQGWVPATYLEP 53

Third 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 third 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: 213012 Cd Length: 54 Bit Score: 59.68 E-value: 2.65e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd12079      2 EYYTIAEFQSCISDGISFRGGQKAEVIEKNSGGWWYVQIGEKEGWAPSSYID 53

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: 59.58 E-value: 3.12e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLEP 865
Cdd:cd12021      2 YRAIADYEKSSKSEMALKTGDVVEVVEKSENGWWFCQLKAKRGWVPASYLEP 53

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: 59.09 E-value: 4.53e-11

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 2551499755  1057 REVYVSIADYRG-DEETMGFPEGTSLEVLEKNPNGWWYCQVLDglqGRKGWVPSNYLE 1113
Cdd:smart00326    2 GPQVRALYDYTAqDPDELSFKKGDIITVLEKSDDGWWKGRLGR---GKEGLFPSNYVE 56

Fifth (C-terminal) 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 fifth (C-terminal) 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: 212953 Cd Length: 57 Bit Score: 58.82 E-value: 5.96e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2551499755  254 YITVQPYtsQGKDE-IGFEKGVTVEVIQKNLEGWWYIRYL----GKEGWAPASYLKK 305
Cdd:cd12020      2 YVSIADY--EGDEEtAGFQEGVSMEVLEKNPNGWWYCQILdgvkPFKGWVPSNYLEK 56

Third 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 third 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: 213012 Cd Length: 54 Bit Score: 58.52 E-value: 5.96e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd12079      2 EYYTIAEFQSCISDGISFRGGQKAEVIEKNSGGWWYVQIGEKEGWAPSSYIDK 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: 58.31 E-value: 7.12e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd12022      2 YITIKAYTAVEEDELTLLEGEAIEVIHKLLDGWWVVRKGEVTGYFPSMYLQK 53

First 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 first 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: 213008 Cd Length: 55 Bit Score: 58.55 E-value: 7.16e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd12075      3 YVVVANYQKQESSEISLYVGQVVDIIEKNESGWWFVSTADEQGWVPATCLE 53

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: 58.12 E-value: 8.64e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLDA 205
Cdd:cd12024      1 LYYATRAYEAQKEDELSVPAGVVVEVLQKSDNGWWLIRYNGRAGYVPSMYLQP 53

Third 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 third 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: 213011 Cd Length: 53 Bit Score: 58.16 E-value: 1.02e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd12078      1 EYYTIADFQTTIPDGISFQAGLKVEVIEKNLSGWWYIQIEDKEGWAPATFID 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: 57.73 E-value: 1.41e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd12077      2 KYVTVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 54

Fourth 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 fourth 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: 212952 Cd Length: 53 Bit Score: 57.30 E-value: 1.78e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYL 303
Cdd:cd12019      2 YMTTSAYQKVQDSEISFPAGVEVEVLEKQESGWWYVRFGELEGWAPSHYL 51

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: 57.38 E-value: 1.79e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11824      2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYL 51

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: 57.27 E-value: 2.06e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755 1060 YVSIADY-RGDEETMGFPEGTSLEVLEKNPNGWWYCQvldgLQGRKGWVPSNYLE 1113
Cdd:cd12021      2 YRAIADYeKSSKSEMALKTGDVVEVVEKSENGWWFCQ----LKAKRGWVPASYLE 52

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: 57.01 E-value: 2.29e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEE--QGWVPATYL 203
Cdd:cd11858      1 TYKALYDFAGSVANELSLKKDDIVYIVQKEDNGWWLAKKLDEskEGWVPAAYL 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: 56.70 E-value: 2.97e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd12016      3 YITTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGKEGWAPATYLK 53

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: 56.66 E-value: 3.24e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755 1060 YVSIADYRGDEET-MGFPEGTSLEVLEKNPNGWWYCQVLDglqgRKGWVPSNYLER 1114
Cdd:cd12015      2 YVVVADYKKQQPNeISLRAGDVVDVIEKNENGWWFVSLED----EQGWVPATYLEP 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: 56.07 E-value: 4.15e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKKL 306
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVEEI 54

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: 56.19 E-value: 4.26e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2551499755 1058 EVYVSIADY--RGDEEtMGFPEGTSLEVLEKNPNGWWYCQvldgLQGRKGWVPSNYLER 1114
Cdd:cd12077      1 EKYVTVQPYtsQGKDE-IGFEKGVTVEVIQKNLEGWWYIR----YLGKEGWAPASYLKK 54

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: 55.93 E-value: 4.57e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYL-GKEGWAPASY 302
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNgGREGLFPANY 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: 55.81 E-value: 5.55e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  152 EQYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd12076      1 EKYTVIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEGWAPASYL 52

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: 55.93 E-value: 6.24e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2551499755 1058 EVYVSIADYRG-DEETMGFPEGTSLEVLEKNPNGWWYCQvldgLQGRKGWVPSNYLER 1114
Cdd:cd12016      1 EKYITTQAYKAeNEDEIGFETGVVVEVIQKNLDGWWKIR----YQGKEGWAPATYLKK 54

First 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 first 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: 213008 Cd Length: 55 Bit Score: 55.47 E-value: 7.56e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYID 503
Cdd:cd12075      2 QYVVVANYQKQESSEISLYVGQVVDIIEKNESGWWFVSTADEQGWVPATCLE 53

Fourth 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 fourth 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: 212952 Cd Length: 53 Bit Score: 55.37 E-value: 8.29e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  453 YYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYID 503
Cdd:cd12019      2 YMTTSAYQKVQDSEISFPAGVEVEVLEKQESGWWYVRFGELEGWAPSHYLE 52

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: 54.77 E-value: 1.20e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd12016      2 KYITTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGKEGWAPATYLKK 54

First 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 first 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: 213008 Cd Length: 55 Bit Score: 55.08 E-value: 1.26e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  252 EKYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd12075      1 DQYVVVANYQKQESSEISLYVGQVVDIIEKNESGWWFVSTADEQGWVPATCLE 53

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: 54.65 E-value: 1.85e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd12077      3 YVTVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 53

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: 54.24 E-value: 1.93e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAE-EQGWVPATYL 203
Cdd:cd11770      2 YEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAENSKgNRGLVPKTYL 52

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: 54.07 E-value: 2.12e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd12022      2 YITIKAYTAVEEDELTLLEGEAIEVIHKLLDGWWVVRKGEVTGYFPSMYL 51

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: 54.07 E-value: 2.25e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  813 LYRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd12022      1 LYITIKAYTAVEEDELTLLEGEAIEVIHKLLDGWWVVRKGEVTGYFPSMYLQ 52

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: 53.75 E-value: 3.21e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAV 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: 53.42 E-value: 3.46e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATY 202
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNY 50

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: 53.36 E-value: 3.46e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIEKSESGWWFV-STAEEQGWVPA 200
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGrNKGGKEGLIPS 47

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: 52.85 E-value: 5.07e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755 1059 VYVSIADYRGDEET-MGFPEGTSLEVLEKNPNGWWYCQVLDglqGRKGWVPSNY 1111
Cdd:cd00174      1 YARALYDYEAQDDDeLSFKKGDIITVLEKDDDGWWEGELNG---GREGLFPANY 51

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: 52.84 E-value: 7.04e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd12017      2 YFTIGEFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKEGWAPSSYIE 52

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

Pssm-ID: 132786 Cd Length: 133 Bit Score: 55.01 E-value: 7.84e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755   25 VYLINVT--YSD--STSHIIYRRYSKFFDLQMQLLDKFPIEGGQKDPKKRIIPFLPGKILFrrshvrdVAMKRLRFiDDY 100
Cdd:cd06876     40 VYLIEVQrlNNDdqSSGWVVARRYSEFLELHKYLKKRYPGVLKLDFPQKRKISLKYSKTLL-------VEERRKAL-EKY 111

                           90       100
                   ....*....|....*....|
gi 2551499755  101 CRALVRLpPQISQSEEVLRF 120
Cdd:cd06876    112 LQELLKI-PEVCEDEEFRKF 130

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: 52.54 E-value: 9.36e-09

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755   812 ALYrttdAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVD-EGWVPTFYLE 864
Cdd:smart00326    7 ALY----DYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGkEGLFPSNYVE 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: 51.77 E-value: 1.80e-08

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755   453 YYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDM-EGWAPCSYI 502
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGkEGLFPSNYV 55

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: 2.53e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2551499755  259 PYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYL-GKEGWAPA 300
Cdd:pfam00018    5 DYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKgGKEGLIPS 47

First 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 first 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: 213007 [Multi-domain] Cd Length: 53 Bit Score: 50.87 E-value: 3.28e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755 1060 YVSIADYRGDEET-MGFPEGTSLEVLEKNPNGWWYCQVLDglqgRKGWVPSNYLE 1113
Cdd:cd12074      2 YVVVSNYEKQENSeISLQAGEVVDVIEKNESGWWFVSTAE----EQGWVPATYLE 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: 50.45 E-value: 4.45e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEK-SESG---WWFVSTAEEQGWVPATYLD 204
Cdd:cd11800      1 YYYALYTFEARSPGELSVTEGQVVTVLEKhDLKGnpeWWLVEDRGKQGYVPSNYLA 56

Fifth (C-terminal) 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 fifth (C-terminal) 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: 212953 Cd Length: 57 Bit Score: 50.34 E-value: 5.36e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2551499755  453 YYTIAEFQScISDGISFRGGQKADVIEKNSGGWWYVQIGD----MEGWAPCSYIDKR 505
Cdd:cd12020      2 YVSIADYEG-DEETAGFQEGVSMEVLEKNPNGWWYCQILDgvkpFKGWVPSNYLEKK 57

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: 49.69 E-value: 8.39e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755  812 ALYrttdAYERAQESELSIPAGVEVEVLEKQESGWWYVRW--GVDEGWVPTFYLEP 865
Cdd:cd11858      4 ALY----DFAGSVANELSLKKDDIVYIVQKEDNGWWLAKKldESKEGWVPAAYLEE 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: 49.31 E-value: 1.05e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755 1065 DYRGDEE-TMGFPEGTSLEVLEKNPNGWWYCQVLDGlqGRKGWVPSNYLER 1114
Cdd:cd11858      7 DFAGSVAnELSLKKDDIVYIVQKEDNGWWLAKKLDE--SKEGWVPAAYLEE 55

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: 49.29 E-value: 1.12e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd11824      1 KYSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYLEK 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: 1.47e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2551499755  164 ENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11828     12 DPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFV 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: 48.80 E-value: 1.58e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASY 302
Cdd:cd11766      8 YEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNY 50

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

Pssm-ID: 132783 Cd Length: 120 Bit Score: 50.73 E-value: 1.87e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755   21 SKHY-VYLINVTYSDST----SHIIYRRYSKFFDLQMQLLDKFpieggqkdPKKRIIPFlPGKILFRRSHvRDVAMKRLR 95
Cdd:cd06873     19 GKTYaVYAISVTRIYPNgqeeSWHVYRRYSDFHDLHMRLKEKF--------PNLSKLSF-PGKKTFNNLD-RAFLEKRRK 88


                   ....*
gi 2551499755   96 FIDDY 100
Cdd:cd06873     89 MLNQY 93

Fourth (C-terminal) 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 fourth (C-terminal) 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: 212951 Cd Length: 56 Bit Score: 48.73 E-value: 2.12e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  154 YVAVANYERQENSEiSLRAGETVDVIEKSESGWWFVSTAEE----QGWVPATYL 203
Cdd:cd12018      2 YVAVADFEGDEDTS-SFKEGTVFEVREKNSSGWWFCKVLSGgpvwEGWIPSNYL 54

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 48.38 E-value: 2.14e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

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: 2.34e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  812 ALYrttdAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVD-EGWVPT 860
Cdd:pfam00018    2 ALY----DYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGGkEGLIPS 47

Third 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 third 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: 213011 Cd Length: 53 Bit Score: 48.53 E-value: 2.53e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755 1060 YVSIADYRGD-EETMGFPEGTSLEVLEKNPNGWWYCQVLDglqgRKGWVPSNYLER 1114
Cdd:cd12078      2 YYTIADFQTTiPDGISFQAGLKVEVIEKNLSGWWYIQIED----KEGWAPATFIDK 53

Third 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 third 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: 213011 Cd Length: 53 Bit Score: 48.15 E-value: 2.66e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd12078      2 YYTIADFQTTIPDGISFQAGLKVEVIEKNLSGWWYIQIEDKEGWAPATFID 52

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: 48.49 E-value: 2.76e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2551499755 1058 EVYVSIADYRG-DEETMGFPEGTSLEVLEKNPNGWWYCQvldgLQGRKGWVPSNYLER 1114
Cdd:cd12076      1 EKYTVIYPYTArDQDEINLEKGAVVEVIQKNLEGWWKIR----YQGKEGWAPASYLKK 54

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: 48.15 E-value: 3.38e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLG--KEGWAPASYLK 304
Cdd:cd11858      8 FAGSVANELSLKKDDIVYIVQKEDNGWWLAKKLDesKEGWVPAAYLE 54

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: 47.98 E-value: 3.47e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755 1059 VYVSIADYRG-DEETMGFPEGTSLEVLEKNPNGWWYCQVldglQGRKGWVPSNYLE 1113
Cdd:pfam07653    1 YGRVIFDYVGtDKNGLTLKKGDVVKVLGKDNDGWWEGET----GGRVGLVPSTAVE 52

Fifth (C-terminal) 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 fifth (C-terminal) 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: 212953 Cd Length: 57 Bit Score: 48.03 E-value: 4.28e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  154 YVAVANYERQENSeISLRAGETVDVIEKSESGWWFVSTAE----EQGWVPATYLD 204
Cdd:cd12020      2 YVSIADYEGDEET-AGFQEGVSMEVLEKNPNGWWYCQILDgvkpFKGWVPSNYLE 55

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: 47.41 E-value: 5.72e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  256 TVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd11827      4 ALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVEK 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: 47.33 E-value: 6.17e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd12076      2 KYTVIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEGWAPASYLKK 54

Fourth 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 fourth 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: 212952 Cd Length: 53 Bit Score: 47.28 E-value: 6.48e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755 1067 RGDEETMGFPEGTSLEVLEKNPNGWWYCQVLDGlqgrKGWVPSNYLE 1113
Cdd:cd12019     10 KVQDSEISFPAGVEVEVLEKQESGWWYVRFGEL----EGWAPSHYLE 52

Third 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 third 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: 213012 Cd Length: 54 Bit Score: 46.96 E-value: 7.21e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd12079      3 YYTIAEFQSCISDGISFRGGQKAEVIEKNSGGWWYVQIGEKEGWAPSSYID 53

Third 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 third 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: 213012 Cd Length: 54 Bit Score: 46.96 E-value: 8.19e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755 1060 YVSIADYRGD-EETMGFPEGTSLEVLEKNPNGWWYCQVLDglqgRKGWVPSNYLER 1114
Cdd:cd12079      3 YYTIAEFQSCiSDGISFRGGQKAEVIEKNSGGWWYVQIGE----KEGWAPSSYIDK 54

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: 46.66 E-value: 8.45e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPAT 201
Cdd:cd11832      1 YFIAVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFPSD 49

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: 46.87 E-value: 8.67e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd12021      2 YRAIADYEKSSKSEMALKTGDVVEVVEKSENGWWFCQLKAKRGWVPASYLE 52

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

Pssm-ID: 132813 Cd Length: 120 Bit Score: 48.86 E-value: 9.48e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    8 DVKVVD---VEKRRHPSKHYVYLINVT--YSDSTSHIIYRRYSKFFDLQMQLLDKFPieggqkDPKKRIIPFLPGKILFr 82
Cdd:cd07280      4 DVNVGDytiVGGDTGGGAYVVWKITIEtkDLIGSSIVAYKRYSEFVQLREALLDEFP------RHKRNEIPQLPPKVPW- 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755   83 rsHVRDVAMKRlRFIDDYCRAL------VRLPPQISQSEEVLRFFET 123
Cdd:cd07280     77 --YDSRVNLNK-AWLEKRRRGLqyflncVLLNPVFGGSPVVKEFLLP 120

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: 46.95 E-value: 9.68e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd12076      3 YTVIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEGWAPASYLK 53

First 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 first 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: 213008 Cd Length: 55 Bit Score: 46.61 E-value: 1.00e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2551499755 1058 EVYVSIADYRGDEET-MGFPEGTSLEVLEKNPNGWWYCQVLDglqgRKGWVPSNYLE 1113
Cdd:cd12075      1 DQYVVVANYQKQESSeISLYVGQVVDIIEKNESGWWFVSTAD----EQGWVPATCLE 53

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

Pssm-ID: 132823 Cd Length: 109 Bit Score: 48.38 E-value: 1.14e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    8 DVKVVDVEKRRHPSKHYVYLINVTySDSTSHIIY--RRYSKFFDLQMQLLDKFPieggqkdpkKRIIPFLPGKILFRRSH 85
Cdd:cd07290      1 DVFLCRHESTFNPSKGYAYVVKVQ-REGHKEATFvqRTFEEFQELHNKLRLLFP---------SSKLPSFPSRFVIGRSR 70

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2551499755   86 VRDVAMKRLRFIDDYCRALVRLPPQISQSEEVLRFF 121
Cdd:cd07290     71 GEAVAERRKEELNGYIWHLIHAPPEVAECDLVYTFF 106

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: 46.12 E-value: 1.43e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755 1059 VYVSIADYRGDEET-MGFPEGTSLEVLEKNPNGWWycqvlDGL------QGRKGWVPSNY 1111
Cdd:cd11883      1 VVVALYDFTPKSKNqLSFKAGDIIYVLNKDPSGWW-----DGViisssgKVKRGWFPSNY 55

Fourth (C-terminal) 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 fourth (C-terminal) 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: 212951 Cd Length: 56 Bit Score: 46.42 E-value: 1.45e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755  453 YYTIAEFQScISDGISFRGGQKADVIEKNSGGWWYVQI----GDMEGWAPCSYIDK 504
Cdd:cd12018      2 YVAVADFEG-DEDTSSFKEGTVFEVREKNSSGWWFCKVlsggPVWEGWIPSNYLRK 56

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: 46.18 E-value: 1.59e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYL 303
Cdd:cd11901     10 YTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYV 53

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: 46.13 E-value: 1.84e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVS--TAEEQGWVPATYL 203
Cdd:cd11857      2 YTVVADYEKGGPDDLTVKSGDLVQLIHEGDEGQWLVKnlSTRKEGWVPAANL 53

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: 46.08 E-value: 1.99e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEG--WWYIRYLGKEGWAPASYL 303
Cdd:cd11952      9 YSAEFPDELSFKEGDMVTVLRKDGEGtdWWWASLCGREGYVPRNYF 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: 45.72 E-value: 2.20e-06

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2551499755 1078 GTSLEVLEKNPNGWWYCQVldglQGRKGWVPSNYLER 1114
Cdd:cd11766     21 GDRVLVLEKSSDGWWRGEC----NGQVGWFPSNYVTE 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: 45.53 E-value: 2.51e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755  812 ALYrttdAYERAQESELSIPAGVEVEVLEKQESGWWYVRW-GVDEGWVP 859
Cdd:cd00174      4 ALY----DYEAQDDDELSFKKGDIITVLEKDDDGWWEGELnGGREGLFP 48

Fifth (C-terminal) 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 fifth (C-terminal) 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: 212953 Cd Length: 57 Bit Score: 45.34 E-value: 2.99e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  807 SDYEGalyrttdayeraQESELSIPAGVEVEVLEKQESGWWYVRW--GVD--EGWVPTFYLE 864
Cdd:cd12020      6 ADYEG------------DEETAGFQEGVSMEVLEKNPNGWWYCQIldGVKpfKGWVPSNYLE 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: 45.27 E-value: 3.02e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFV---STAEEqGWVPATY 202
Cdd:cd11845      1 IYVALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLArhlSTGKE-GYIPSNY 52

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 44.91 E-value: 3.54e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  257 VQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:pfam14604    2 LYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

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: 44.80 E-value: 4.90e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11833      2 YVALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIEDRVGFFPANFV 51

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: 44.58 E-value: 5.08e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIEKSESGWW--FV---STAEEQGWVPATY 202
Cdd:cd11883      3 VALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWdgVIissSGKVKRGWFPSNY 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: 44.33 E-value: 6.26e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11840      1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVE 52

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: 44.18 E-value: 7.44e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  453 YYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYID 503
Cdd:cd12021      2 YRAIADYEKSSKSEMALKTGDVVEVVEKSENGWWFCQLKAKRGWVPASYLE 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: 43.92 E-value: 8.39e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11806      2 YVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIPASHL 51

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: 43.90 E-value: 8.75e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2551499755  823 AQES-ELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd11824     10 AQEDdELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYLE 52

Fourth (C-terminal) 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 fourth (C-terminal) 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: 212951 Cd Length: 56 Bit Score: 44.11 E-value: 8.83e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755  265 KDEIGFEKGVTVEVIQKNLEGWWYIRYLGK----EGWAPASYLKK 305
Cdd:cd12018     12 EDTSSFKEGTVFEVREKNSSGWWFCKVLSGgpvwEGWIPSNYLRK 56

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: 8.99e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755 1059 VYVSIADYRG-DEETMGFPEGTSLEVLEKNPNGWWYCQvldgLQGRKGWVPSNYL 1112
Cdd:cd11806      1 EYVAIADFVAtDDSQLSFESGDKLLVLRKPSVDWWWAE----HNGCCGYIPASHL 51

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: 44.01 E-value: 9.38e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11808      3 VALYDYQEKSPREVSMKKGDILTLLNSSNKDWWKVEVNDRQGFVPAAYV 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: 43.79 E-value: 9.52e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2551499755  820 YERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLEP 865
Cdd:cd11766      8 YEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYVTE 53

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: 43.87 E-value: 1.07e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd11823      1 RCKALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVE 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: 43.86 E-value: 1.10e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755 1060 YVSIADY---RGDEetMGFPEGTSLEVLEKNPNGWWYCQvldgLQGRKGWVPSNYL 1112
Cdd:cd12024      2 YYATRAYeaqKEDE--LSVPAGVVVEVLQKSDNGWWLIR----YNGRAGYVPSMYL 51

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: 43.83 E-value: 1.11e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLDA 205
Cdd:cd11772      2 FRALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYVEE 53

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: 43.82 E-value: 1.26e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755  266 DEIGFEKGVTVEVIQKN---LEGWWYIRYLGKEGWAPASYLKKL 306
Cdd:cd12002     14 EELAFRKGDILTVIEQNtggLEGWWLCSLHGRQGIAPGNRLKLL 57

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: 43.46 E-value: 1.50e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAE-EQGWVPATYL 203
Cdd:cd11908      4 IALYDYQTNDPQELALRYNEEYHLLDSSEIHWWRVQDKNgHEGYVPSSYL 53

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: 43.49 E-value: 1.54e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2551499755  266 DEIGFEKGVTVEVIQKN---LEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11844     14 DELAFRRGDILTVLEQNtagLEGWWLCSLRGRQGIAPGNRLK 55

The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles.

Pssm-ID: 132776 Cd Length: 105 Bit Score: 44.91 E-value: 1.73e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755   22 KHYVYLInvtYSDSTSHIIYRRYSKFFDLQMQLLDKFPIeggqkdpkkRIIPFLPGKILFrrshvrdVAMKRlRFIDDYC 101
Cdd:cd06866     17 KHVEYEV---SSKRFKSTVYRRYSDFVWLHEYLLKRYPY---------RMVPALPPKRIG-------GSADR-EFLEARR 76

                           90       100
                   ....*....|....*....|....*....
gi 2551499755  102 RALVRLPPQIS-----QSEEVLRFFETKP 125
Cdd:cd06866     77 RGLSRFLNLVArhpvlSEDELVRTFLTEP 105

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: 42.81 E-value: 2.18e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPA 300
Cdd:cd11832      1 YFIAVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFPS 48

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: 43.02 E-value: 2.29e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  812 ALYrttdAYERAQESELSIPAGVEVEVLEK-QESGWWYVRWG-VDEGWVPTFYLE 864
Cdd:cd11911      4 ALY----DFDGTSEGTLSMEEGEILLVLEEdGGDGWTRVRKNnGDEGYVPTSYIE 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: 42.67 E-value: 2.32e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2551499755 1059 VYVSIADYRG---DEetMGFPEGTSLEVLEKNPNGWWYCQvldgLQGRKGWVPSNYLE 1113
Cdd:cd11772      1 VFRALYDYEAqhpDE--LSFEEGDLLYISDKSDPNWWKAT----CGGKTGLIPSNYVE 52

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: 42.58 E-value: 2.47e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755 1061 VSIADYRG-DEETMGFPEGTSLEVLEKNPNGWWYCQVLDglqGRKGWVPS 1109
Cdd:pfam00018    1 VALYDYTAqEPDELSFKKGDIIIVLEKSEDGWWKGRNKG---GKEGLIPS 47

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: 42.76 E-value: 2.55e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYL 303
Cdd:cd11806      2 YVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIPASHL 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: 42.71 E-value: 2.56e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755  259 PYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASY 302
Cdd:cd11823      7 SYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATY 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: 43.06 E-value: 2.62e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGwWFVSTAEEQ---GWVPATYL 203
Cdd:cd11916      4 YQALYSYAPQNDDELELRDGDIVDVMEKCDDG-WFVGTSRRTkqfGTFPGNYV 55

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: 42.60 E-value: 2.92e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  160 YERQENSEISLRAGETVDVIEKSE-SGWWFV-STAEEQGWVPATYLD 204
Cdd:cd11912      8 YTASGDDEVSISEGEEVTVLEPDDgSGWTKVrNGSGEEGLVPTSYIE 54

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: 42.68 E-value: 2.94e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYL 303
Cdd:cd11902      9 YVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIGWFPSNYV 52

Src homology 3 domain of Obscurin and similar proteins; Obscurin is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212958 Cd Length: 63 Bit Score: 42.95 E-value: 3.02e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2551499755  154 YVAVANY--ERQENSEISLRAGETVDVIEKSESGWWFVST------AEEQGWVPATYLD 204
Cdd:cd12025      4 YIVTADYtpDGADTEAIPLEEGQYVEVLDSAHPLKWLVRTkptkssPPRQGWVSPAYLE 62

First or N-terminal Src homology 3 domain of 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 first SH3 domain (or N-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: 212956 Cd Length: 56 Bit Score: 42.55 E-value: 3.09e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  154 YVAVANYERQE--NSEISLRAGETVDVIEKSESGWWFVSTAEEQ-GWVPATYLDA 205
Cdd:cd12023      2 YRCLAPFETKDtkNKPFKAAAQESLDVLLKDPTGWWLVENEDRQiAWFPAPYLEE 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: 42.29 E-value: 3.24e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGwWFVSTAEEQG 196
Cdd:cd11780      2 YRALYSYTPQNEDELELREGDIVYVMEKCDDG-WFVGTSERTG 43

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: 42.55 E-value: 3.32e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNL--EGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd11988      4 YRALYPFEARNHDEMSFNAGDIIQVDEKTVgePGWLYGSFQGNFGWFPCNYVEK 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: 42.18 E-value: 3.45e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYL--GKEGWAPASY 302
Cdd:cd11845      2 YVALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARHLstGKEGYIPSNY 52

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: 42.06 E-value: 3.52e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  453 YYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDM-EGWAPCSY 501
Cdd:cd00174      2 ARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNGGrEGLFPANY 51

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: 42.22 E-value: 3.54e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEK--SESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11952      5 ALWDYSAEFPDELSFKEGDMVTVLRKdgEGTDWWWASLCGREGYVPRNYF 54

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: 42.31 E-value: 3.69e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEK---SESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11954      5 ALWDYEAQNADELSFQEGDAITILRRkddSETEWWWARLNDKEGYVPKNLL 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: 42.35 E-value: 3.76e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKnLEGWWYIRYL-GKEGWAPASYLK 304
Cdd:cd11837      1 TATALYPWRAKKENHLSFAKGDIITVLEQ-QEMWWFGELEgGEEGWFPKSYVK 52

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: 42.25 E-value: 3.91e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGwWFVSTAEEQ---GWVPATYL 203
Cdd:cd11918      4 YKAVYQYRPQNEDELELREGDRVDVMQQCDDG-WFVGVSRRTqkfGTFPGNYV 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: 42.39 E-value: 4.35e-05

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                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11975      9 AVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDDEEGWFPASFV 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: 42.30 E-value: 4.44e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKKLK 307
Cdd:cd12060     10 FKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYVREIK 57

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 41.83 E-value: 4.46e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755 1065 DYRGDEEtMGFPEGTSLEVLEKNPNGWWYCQvldgLQGRKGWVPSNYLE 1113
Cdd:pfam14604    6 EPKDDDE-LSLQRGDVITVIEESEDGWWEGI----NTGRTGLVPANYVE 49

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: 42.02 E-value: 4.70e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755 1062 SIADYRG-DEETMGFPEGTSLEVLEKNPNGWWycqvLDGLQGRKGWVPSNYLER 1114
Cdd:cd11827      4 ALYAYDAqDTDELSFNEGDIIEILKEDPSGWW----TGRLRGKEGLFPGNYVEK 53

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: 42.03 E-value: 4.87e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFV-------STAEEQGWVPATY 202
Cdd:cd11773      2 YKALYDYEPQTEDELTIQEDDILYLLEKSDDDWWKVklkvnssDDDEPVGLVPATY 57

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: 41.95 E-value: 5.58e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755 1057 REVYVSIADYrgdEETMGFPEGTSLEVLEKNP---NGWWYCQvldgLQGRKGWVPSNYLE 1113
Cdd:cd11844      3 RALYDNVAES---PDELAFRRGDILTVLEQNTaglEGWWLCS----LRGRQGIAPGNRLK 55

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: 5.64e-05

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                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAE-EQGWVPATYL 203
Cdd:cd11768      3 VALYDFQPIEPGDLPLEKGEEYVVLDDSNEHWWRARDKNgNEGYIPSNYV 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: 41.94 E-value: 5.67e-05

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                   ....*....|....*....|....*....|....*....|....*
gi 2551499755  159 NYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11901      9 NYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYV 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: 41.54 E-value: 6.75e-05

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                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPA 200
Cdd:cd11982      3 FMAVKPYQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVGWFPS 49

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: 41.52 E-value: 7.03e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755  259 PYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYL 303
Cdd:cd11772      7 DYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYV 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: 41.53 E-value: 7.44e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755 1060 YVSIADYRGDEET-MGFPEGTSLEVLEKNPNGWWYCQvldGLQGRKGWVPSNYLE 1113
Cdd:cd11770      2 YEALSDFQAEQEGdLSFKKGEVLRIISKRADGWWLAE---NSKGNRGLVPKTYLK 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: 41.20 E-value: 7.87e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11974      5 ALWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNEDREAWFPASFV 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: 41.49 E-value: 8.06e-05

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                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755 1069 DEETMGFPEGTSLEVLEK-----NPNGWWYCQVLDGlqgRKGWVPSNYLE 1113
Cdd:cd11771     13 PEMELSLKKGDIVAVLSKtdplgRDSEWWKGRTRDG---RIGWFPSNYVE 59

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: 41.93 E-value: 8.51e-05

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2551499755  267 EIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11973     33 ELGFKAGDVIEVMDATNKEWWWGRVLDSEGWFPASFVR 70

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: 41.15 E-value: 8.72e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPA 300
Cdd:cd11982      3 FMAVKPYQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVGWFPS 49

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: 41.15 E-value: 8.90e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2551499755  259 PYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11877      7 NFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVK 52

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: 41.12 E-value: 9.18e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYL--GKEGWAPASYL 303
Cdd:cd11857      1 KYTVVADYEKGGPDDLTVKSGDLVQLIHEGDEGQWLVKNLstRKEGWVPAANL 53

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: 41.14 E-value: 9.23e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYI-RYLGKEGWAPASYLKK 305
Cdd:cd11770      2 YEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAeNSKGNRGLVPKTYLKV 54

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: 41.09 E-value: 9.27e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLDA 205
Cdd:cd11964      5 AIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGLFPSNFVTA 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: 41.32 E-value: 9.38e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAE-EQGWVPATYLD 204
Cdd:cd11962      3 VVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGTNSKgESGLFPSNYVE 53

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: 41.17 E-value: 9.51e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755 1068 GDEETMGFPEGTSLEVLEKNPNG--WWYCQVLDGLQgrkGWVPSNYL 1112
Cdd:cd11904     12 SNDEELNFEKGEVMDVIEKPENDpeWWKCRKANGQV---GLVPKNYV 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: 41.15 E-value: 1.12e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  252 EKYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKKL 306
Cdd:cd11972      3 EKVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVESI 57

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: 41.04 E-value: 1.14e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLEPI 866
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVEEI 54

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: 40.82 E-value: 1.16e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKKL 306
Cdd:cd12061      8 FQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVREI 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: 40.78 E-value: 1.17e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  257 VQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYL--GKEGWAPASY 302
Cdd:cd11793      5 VHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGERLrdGERGWFPSSY 52

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: 40.70 E-value: 1.25e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPA 300
Cdd:cd11984      2 TFIAVKAYSPQGEGEIQLNRGERVKVLSIGEGGFWEGTVKGRTGWFPA 49

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: 40.70 E-value: 1.25e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPA 200
Cdd:cd11984      3 FIAVKAYSPQGEGEIQLNRGERVKVLSIGEGGFWEGTVKGRTGWFPA 49

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: 40.48 E-value: 1.33e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd11827      4 ALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVE 52

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: 40.83 E-value: 1.42e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEK---SESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11807      5 ALFDYEAENGDELSFREGDELTVLRKgddDETEWWWARLNDKEGYVPRNLL 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: 40.75 E-value: 1.52e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2551499755  252 EKYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWY--IRYLGKEGWAPASYLKKL 306
Cdd:cd11934      3 KRYRAVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYgtVERTGDTGMLPANYVEAI 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: 40.81 E-value: 1.64e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  256 TVQPYTSQGKDEIGFEKGVTVEVIQK--NLEGWWYIR-YLGKEGWAPASYL 303
Cdd:cd11903      5 TLYPFSSVTEEELNFEKGETMEVIEKpeNDPEWWKCKnSRGQVGLVPKNYV 55

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: 40.42 E-value: 1.65e-04

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVS--TAEEQGWVPATYL 203
Cdd:cd12006      3 FVALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARslTTGETGYIPSNYV 54

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: 40.36 E-value: 1.71e-04

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  255 ITVQPYTSQGKDEIGFEKGVTVEVIQKNLEgWWYIRYLG--KEGWAPASYLKKL 306
Cdd:cd12004      3 VALYPYDGIHEDDLSFKKGEKLKVIEEHGE-WWKARSLTtkKEGFIPSNYVAKV 55

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: 40.38 E-value: 1.74e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755 1061 VSIADYRGD-EETMGFPEGTSLEVLEKNPNGWWycqvlDG-LQGRKGWVPSNYLE 1113
Cdd:cd11826      3 VALYDYTADkDDELSFQEGDIIYVTKKNDDGWY-----EGvLNGVTGLFPGNYVE 52

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

Pssm-ID: 132806 Cd Length: 101 Bit Score: 41.82 E-value: 1.77e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755   24 YVYLINVTYSDSTSHIIYRRYSKFFDLQMQLLDKFPIEGGQKDPKKRIIPFlpgkilfrrshvRDVAMKRLRFIDDYCRA 103
Cdd:cd06896     13 NLYLVQVTQSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPF------------TDSDHKRVRDLNHYLEQ 80

                           90
                   ....*....|....*...
gi 2551499755  104 LVRLPPQISQSEEVLRFF 121
Cdd:cd06896     81 LLSGSREVANSDCVLSFF 98

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: 40.43 E-value: 1.77e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755 1070 EETMGFPEGTSLEVLEKNPNG--WWYCQvldGLQGRKGWVPSNYL 1112
Cdd:cd11903     14 EEELNFEKGETMEVIEKPENDpeWWKCK---NSRGQVGLVPKNYV 55

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: 40.38 E-value: 1.88e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2551499755 1056 LREVYvsiaDYRGDEE-TMGFPEGTSLEVLEKNPNGWWycQVLDgLQGRKGWVPSNYLE 1113
Cdd:cd11849      2 YRALY----DFKSAEPnTLSFSEGETFLLLERSNAHWW--LVTN-HSGETGYVPANYVK 53

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: 40.14 E-value: 2.17e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFV-STAEEQGWVPATYL 203
Cdd:cd11774      4 ALYDYDKQTEEELSFNEGDTLDVYDDSDSDWILVgFNGTQFGFVPANYI 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: 39.94 E-value: 2.20e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  155 VAVANYERQENSE--ISLRAGETVDVIEKSE-SGWWFVSTAE-EQGWVPATYLD 204
Cdd:cd11911      1 TCTALYDFDGTSEgtLSMEEGEILLVLEEDGgDGWTRVRKNNgDEGYVPTSYIE 54

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: 40.06 E-value: 2.27e-04

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2551499755  464 SDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYI 502
Cdd:cd11828     13 PEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFV 51

SH3 domain protein; Members of this protein family have a signal peptide, a strongly conserved SH3 domain, a variable region, and then a C-terminal hydrophobic transmembrane alpha helix region.

Pssm-ID: 275056 [Multi-domain] Cd Length: 198 Bit Score: 43.46 E-value: 2.29e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755  829 SIPAGVEVEVLEKQESGWWYVRWGVD-EGWVPTFYLepIRQPSDAGISESHDGSLAELsnTSKSNSL-EKNEQRVQALNN 906
Cdd:TIGR04211   23 SLKSGTPVTVLERSEDGYSRVRTPKGrEGWVLSRYL--SDTPSARERLPELQQELAEL--QEELAELqEQLAELRQENQE 98


                   ....*
gi 2551499755  907 LNQQN 911
Cdd:TIGR04211   99 LKQQL 103

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: 39.95 E-value: 2.40e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755  160 YERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd12054      9 YVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFV 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: 39.95 E-value: 2.40e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  158 ANYE---RQENSEISLRAGETVDVIEKS-----ESGWWFVSTAE-EQGWVPATYL 203
Cdd:cd11771      4 ALYDftpENPEMELSLKKGDIVAVLSKTdplgrDSEWWKGRTRDgRIGWFPSNYV 58

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: 2.66e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  255 ITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd12073      4 VALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGLFPANYVE 53

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: 39.59 E-value: 2.71e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  814 YRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLEP 865
Cdd:cd11772      2 FRALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYVEE 53

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: 40.02 E-value: 2.79e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755  820 YERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYL 863
Cdd:cd11901     10 YTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYV 53

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

Pssm-ID: 132779 Cd Length: 119 Bit Score: 41.50 E-value: 2.80e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    2 QLRTVLDVKVVDVEKRRHpskHYVYLINVTYSDSTSHIIY--RRYSKFFDLQMQLLDKFPieggqkdpkKRIIPFLPGKi 79
Cdd:cd06869     15 TAGRLSSKKAYFVNRSKH---HYEFIIRVRREGEEYRTIYvaRRYSDFKKLHHDLKKEFP---------GKKLPKLPHK- 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2551499755   80 lfrrshvRDVAMKRLR-FIDDYCRALVRlPPQISQSEEVLRFF 121
Cdd:cd06869     82 -------DKLPREKLRlSLRQYLRSLLK-DPEVAHSSILQEFL 116

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: 39.65 E-value: 2.99e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKG--VTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd11836      1 KYRALYAFEARNPDEISFQPGdiIQVDESQVAEPGWLAGELKGKTGWFPANYVEK 55

Uncharacterized conserved protein YraI [Function unknown];

Pssm-ID: 444015 [Multi-domain] Cd Length: 92 Bit Score: 40.82 E-value: 3.26e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2551499755  169 SLRAGETVDVIE-KSESGWWFVSTAEEQGWVPATYLDAQTGTR 210
Cdd:COG4991     46 TLPAGATVTVLGcTSGGGWCKVSYGGQRGWVSARYLQVSYDGQ 88

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: 39.68 E-value: 3.35e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  452 EYYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYI 502
Cdd:cd11806      1 EYVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIPASHL 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: 39.56 E-value: 3.44e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2551499755  459 FQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd11766      8 YEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYVTE 53

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: 39.63 E-value: 3.54e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  257 VQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWY--IRYLGKE---GWAPASYLKK 305
Cdd:cd11839      5 IAPFTATAENQLSLAVGQLVLVRKKSPSGWWEgeLQARGKKrqiGWFPANYVKL 58

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: 39.66 E-value: 3.56e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2551499755  159 NYERQENSEISLRAGETVDVIEKSESGWWFV--STAEEQGWVPATY 202
Cdd:cd11888      9 EYTGKDGRKVSIKEGERFLLLKKSNDDWWQVrrPGDSKPFYVPAQY 54

Uncharacterized conserved protein YraI [Function unknown];

Pssm-ID: 444015 [Multi-domain] Cd Length: 92 Bit Score: 40.43 E-value: 3.74e-04

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2551499755 1076 PEGTSLEVLEKNPNGWWyCQVldGLQGRKGWVPSNYL 1112
Cdd:COG4991     48 PAGATVTVLGCTSGGGW-CKV--SYGGQRGWVSARYL 81

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: 39.21 E-value: 4.03e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKK 305
Cdd:cd12055      8 YLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIKE 53

Uncharacterized conserved protein YraI [Function unknown];

Pssm-ID: 444015 [Multi-domain] Cd Length: 92 Bit Score: 40.43 E-value: 4.04e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2551499755  829 SIPAGVEVEVLE-KQESGWWYVRWGVDEGWVPTFYLEPIRQ 868
Cdd:COG4991     46 TLPAGATVTVLGcTSGGGWCKVSYGGQRGWVSARYLQVSYD 86

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: 39.15 E-value: 4.19e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  155 VAVANYE--RQENSEISLRAGETVDVIEK-SESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd11830      1 TAKARYDfcARDMRELSLKEGDVVKIYNKkGQQGWWRGEINGRIGWFPSTYVE 53

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: 39.25 E-value: 4.26e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2551499755 1070 EETMGFPEGTSLEVLEKNPNGWWYcqvlDGLQGRKGWVPSNYL 1112
Cdd:cd11901     15 EDELSLVKGTKVIVMEKCSDGWWR----GSYNGQVGWFPSNYV 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: 39.28 E-value: 4.67e-04

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2551499755  267 EIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11974     16 ELAFKAGDVIRVLEASNKDWWWGRNEDREAWFPASFVR 53

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: 39.21 E-value: 4.81e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  152 EQYVAVANYERQENSEISLRAGETVDVIEKSESGwWFVSTAEEQ---GWVPATYL 203
Cdd:cd11917      5 EPFQALYNYMPRNEDELELREGDVIDVMEKCDDG-WFVGTSRRTkffGTFPGNYV 58

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.

Pssm-ID: 132810 Cd Length: 118 Bit Score: 41.18 E-value: 4.82e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755   18 RHPSKHYVYLINVTYSDsTSHIIYRRYSKFFDLQMQLLDKFPIEGGQKDPKKRII 72
Cdd:cd07277     13 KGSDAHHVYQVYIRIRD-DEWNVYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAI 66

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: 39.04 E-value: 4.85e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLDAQ 206
Cdd:cd12073      4 VALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGLFPANYVELL 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: 39.21 E-value: 4.98e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755  152 EQYVAVANYERQENSEISLRAGETVDVIEKSESGWWF--VSTAEEQGWVPATYLDA 205
Cdd:cd11934      3 KRYRAVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYgtVERTGDTGMLPANYVEA 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: 39.17 E-value: 4.99e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  255 ITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11995      4 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQVGLFPSNYVK 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: 38.90 E-value: 4.99e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  254 YITVQPytsqgkDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11828      8 HVTMDP------EELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVR 52

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: 39.08 E-value: 5.02e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755 1059 VYVSIADY--RGDEEtMGFPEGTSLEVLEKNPNgWWYCQVLDGLQGR--KGWVPSNYLER 1114
Cdd:cd11847      1 IYKALWDFkaRGDEE-LSFQAGDQFRIAERSGD-WWTALKLDRAGGVvaQGFVPNNYLAR 58

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: 38.99 E-value: 5.18e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLDA 205
Cdd:cd11820      5 ALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGLFPANFVTA 54

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: 39.13 E-value: 5.36e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  812 ALYrttdAYERAQESELSIPAGVEVEVLEKQE-SGWWYVRWG-VDEGWVPTFYLE 864
Cdd:cd11912      4 VLY----DYTASGDDEVSISEGEEVTVLEPDDgSGWTKVRNGsGEEGLVPTSYIE 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: 38.84 E-value: 5.38e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  253 KYITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASY 302
Cdd:cd11826      1 KVVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNY 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: 38.90 E-value: 5.44e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755  159 NYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd12061      7 NFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYV 51

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: 39.25 E-value: 5.65e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAE--EQGWVPATYL 203
Cdd:cd12007      3 FVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIAtgKNGYIPSNYV 54

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: 38.83 E-value: 5.73e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755  819 AYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYL 863
Cdd:cd11902      8 AYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIGWFPSNYV 52

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: 38.72 E-value: 6.16e-04

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2551499755  464 SDGISFRGGQKADVIEKNSGGWWYVQ-IGDMEGWAPC 499
Cdd:pfam00018   11 PDELSFKKGDIIIVLEKSEDGWWKGRnKGGKEGLIPS 47

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: 38.84 E-value: 6.33e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIEK--SESGWWFVSTAEEQGWVPATYLDAQ 206
Cdd:cd11977      4 VARYNFAARDMRELSLREGDVVRIYSRigGDQGWWKGETNGRIGWFPSTYVEEE 57

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: 38.76 E-value: 6.43e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATY 202
Cdd:cd11805      4 ALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANY 50

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: 38.86 E-value: 6.56e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  812 ALYrttdAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd11823      4 ALY----SYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVE 52

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: 38.79 E-value: 6.75e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLKKL 306
Cdd:cd12054      9 YVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVKEL 55

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: 38.76 E-value: 6.75e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPA 200
Cdd:cd11983      3 FVVVKSYQPQVEGEIPLHKGDRVKVLSIGEGGFWEGSARGHVGWFPA 49

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: 38.77 E-value: 7.13e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKS-----ESGWWFVSTAEEQGWVPATYL 203
Cdd:cd12058      2 WTALYDYEASGEDELSLRRGDVVEVLSQDaavsgDDGWWAGKIRHRLGIFPANYV 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: 38.47 E-value: 7.50e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2551499755  259 PYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11874      7 SYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVK 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: 38.45 E-value: 7.53e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATY 202
Cdd:cd11877      4 AKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNY 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: 38.46 E-value: 7.55e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVI-EKSESGWWF-VSTAEEQGWVPATY 202
Cdd:cd11763      1 KVRALYDFDSQPSGELSLRAGEVLTITrQDVGDGWLEgRNSRGEVGLFPSSY 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: 38.84 E-value: 7.94e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2551499755 1058 EVYVSIADYRGD-EETMGFPEGTSLEVLEKNPNGwWYCQVLDGLqgrKGWVPSNYLE 1113
Cdd:cd11972      3 EKVVAIYDYTKDkEDELSFQEGAIIYVIKKNDDG-WYEGVMNGV---TGLFPGNYVE 55

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: 38.55 E-value: 8.01e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVS--TAEEQGWVPATYL 203
Cdd:cd12008      2 FVALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHslTTGQTGYIPSNYV 53

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: 39.23 E-value: 8.46e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11973     22 ALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRVLDSEGWFPASFV 69

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: 38.51 E-value: 8.67e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQK-NLEG---WWYIRYLGKEGWAPASYLKK 305
Cdd:cd11800      2 YYALYTFEARSPGELSVTEGQVVTVLEKhDLKGnpeWWLVEDRGKQGYVPSNYLAK 57

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: 38.45 E-value: 8.73e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755  152 EQYVAVANYERQENSEISLRAGETVDVIEKSESG-WWFVSTAE--EQGWVPATYLD 204
Cdd:cd11775      1 KRGKVLYDFDAQSDDELTVKEGDVVYILDDKKSKdWWMVENVStgKEGVVPASYIE 56

Uncharacterized conserved protein YraI [Function unknown];

Pssm-ID: 444015 [Multi-domain] Cd Length: 92 Bit Score: 39.66 E-value: 8.82e-04

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2551499755  272 KGVTVEVI-QKNLEGWWYIRYLGKEGWAPASYLKKLKD 308
Cdd:COG4991     49 AGATVTVLgCTSGGGWCKVSYGGQRGWVSARYLQVSYD 86

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: 38.45 E-value: 9.05e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQ-GWVPATY 202
Cdd:cd11819      3 KALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNAKGQkGLFPANY 51

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: 38.47 E-value: 9.20e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  256 TVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGK-EGWAPASYLKK 305
Cdd:cd11825      4 ALYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKkQKWFPANYVEE 54

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: 9.23e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  256 TVQ---PYTSQGKDEIGFEKGVTVEVIQK--NLEGWWYIRYL-GKEGWAPASYL 303
Cdd:cd11904      2 VVQalyPFSSSNDEELNFEKGEVMDVIEKpeNDPEWWKCRKAnGQVGLVPKNYV 55

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: 38.38 E-value: 9.39e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIE-KSESGW-WFVSTAEEQGWVPATYLD 204
Cdd:cd11999      6 AVYDYTGQEPDELSFKAGEELLKVEdEDEQGWcKGVTDGGAVGLYPANYVE 56

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: 38.45 E-value: 9.56e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755  160 YERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11902      9 YVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIGWFPSNYV 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: 38.39 E-value: 9.62e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  159 NYERQENSEISLRAGETVDVI-EKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd11976      7 DFCARDRSELSLKEGDIIKILnKKGQQGWWRGEIYGRVGWFPANYVE 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: 38.16 E-value: 9.63e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  812 ALYrttdAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYLE 864
Cdd:cd11827      4 ALY----AYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVE 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: 38.43 E-value: 1.00e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEG-WAPASYLKKL 306
Cdd:cd11970     12 YKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEEI 59

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

Pssm-ID: 132780 Cd Length: 109 Bit Score: 39.70 E-value: 1.01e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755    8 DVKVVDVEKRRHPSKHYVYLINVTySDSTSHIIYRRYSKFFDLQMQLLDKFPIEGGQkdpkkriipfLPGKILFRRSHVR 87
Cdd:cd06870      5 VSIPSSDEDREKKKRFTVYKVVVS-VGRSSWFVFRRYAEFDKLYESLKKQFPASNLK----------IPGKRLFGNNFDP 73

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2551499755   88 DVAMKRLRFIDDYCRALVRlPPQISQSEEVLRFF 121
Cdd:cd06870     74 DFIKQRRAGLDEFIQRLVS-DPKLLNHPDVRAFL 106

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: 38.06 E-value: 1.01e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755 1065 DYRG-DEETMGFPEGTSLEVLEKNPNGWWycqvlDG-LQGRKGWVPSNYLE 1113
Cdd:cd11877      7 NFEGtNEDELSFDKGDIITVTQVVEGGWW-----EGtLNGKTGWFPSNYVK 52

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

Pssm-ID: 132784 Cd Length: 127 Bit Score: 40.06 E-value: 1.08e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755   23 HYVYLINVTYSDSTsHIIYRRYSKFFDLQMQLLDKFPIEGGqkdpkkriIPFLPGKILFRRShvRDVAMKRLRFIDDYCR 102
Cdd:cd06874     18 HFEFEVKITVLDET-WTVFRRYSRFRELHKTMKLKYPEVAA--------LEFPPKKLFGNKS--ERVAKERRRQLETYLR 86

                           90
                   ....*....|..
gi 2551499755  103 ALVRLPPQISQS 114
Cdd:cd06874     87 NFFSVCLKLPAC 98

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: 38.09 E-value: 1.09e-03

                           10        20        30
                   ....*....|....*....|....*....|...
gi 2551499755 1083 VLEKNPNGWWY--CQVlDGLQGRKGWVPSNYLE 1113
Cdd:cd11839     26 VRKKSPSGWWEgeLQA-RGKKRQIGWFPANYVK 57

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: 38.02 E-value: 1.10e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  255 ITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIR-YLGKEGWAPASYLKK 305
Cdd:cd11768      3 VALYDFQPIEPGDLPLEKGEEYVVLDDSNEHWWRARdKNGNEGYIPSNYVTE 54

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: 37.97 E-value: 1.10e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11986      2 FVALYRFKALEKDDLDFHPGERITVIDDSNEEWWRGKIGEKTGYFPMNFI 51

SH3 domain protein; Members of this protein family have a signal peptide, a strongly conserved SH3 domain, a variable region, and then a C-terminal hydrophobic transmembrane alpha helix region.

Pssm-ID: 275056 [Multi-domain] Cd Length: 198 Bit Score: 41.53 E-value: 1.11e-03

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 2551499755 1078 GTSLEVLEKNPNGWwyCQVLDGlQGRKGWVPSNYL 1112
Cdd:TIGR04211   27 GTPVTVLERSEDGY--SRVRTP-KGREGWVLSRYL 58

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: 37.90 E-value: 1.16e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2551499755  453 YYTIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd12022      2 YITIKAYTAVEEDELTLLEGEAIEVIHKLLDGWWVVRKGEVTGYFPSMYLQK 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: 38.26 E-value: 1.21e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKS-----ESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11876      2 WTALFDYDARGEDELTLRRGQPVEVLSKDaavsgDEGWWTGKIGDKVGIFPSNYV 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: 38.08 E-value: 1.22e-03

                           10        20
                   ....*....|....*....|....*...
gi 2551499755  160 YERQENSEISLRAGETVDVIEKSESGWW 187
Cdd:cd11874      8 YTPQNEDELELKVGDTIEVLGEVEEGWW 35

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: 38.06 E-value: 1.31e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755  159 NYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd12060      9 NFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYV 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: 38.00 E-value: 1.35e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11985      2 YVALYKFLPQENNDLPLQPGDRVMVVDDSNEDWWKGKSGDRVGFFPANFV 51

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: 37.88 E-value: 1.35e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYL-GKEGWAPASYL 303
Cdd:cd11812      8 YTANRSDELTIHRGDIIRVLYKDNDNWWFGSLVnGQQGYFPANYV 52

The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of fungal proteins similar to Saccharomyces cerevisiae Vam7p. They contain an N-terminal PX domain and a C-terminal SNARE domain. The SNARE (Soluble NSF attachment protein receptor) family of proteins are integral membrane proteins that serve as key factors for vesicular trafficking. Vam7p is anchored at the vacuolar membrane through the specific interaction of its PX domain with phosphatidylinositol-3-phosphate (PI3P) present in bilayers. It plays an essential role in vacuole fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

Pssm-ID: 132807 Cd Length: 108 Bit Score: 39.56 E-value: 1.37e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755    7 LDVKVVDVEkrRHPSKHYVYLINVTYSDStSHIIYRRYSKFFDLQMQLLDKFPIEGGQKDPKKRII 72
Cdd:cd06897      1 LEISIPTTS--VSPKPYTVYNIQVRLPLR-SYTVSRRYSEFVALHKQLESEVGIEPPYPLPPKSWF 63

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: 37.71 E-value: 1.37e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755 1064 ADY-----RGDEETMGfpEGTSLEVLEKNPNGWWYCQvldgLQGRKGWVPSNYLE 1113
Cdd:cd11823      4 ALYsytanREDELSLQ--PGDIIEVHEKQDDGWWLGE----LNGKKGIFPATYVE 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: 37.78 E-value: 1.42e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKsESGWWFVSTAEEQGWVPATY 202
Cdd:cd11838      1 EYIALYPYESNEPGDLTFNAGDVILVTKK-DGEWWTGTIGDRTGIFPSNY 49

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: 37.92 E-value: 1.45e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEE-----QGWVPATYL 203
Cdd:cd11847      2 YKALWDFKARGDEELSFQAGDQFRIAERSGDWWTALKLDRAggvvaQGFVPNNYL 56

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: 37.90 E-value: 1.45e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLDA 205
Cdd:cd11949      4 ALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVTP 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: 37.68 E-value: 1.47e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAE-EQGWVPATYL 203
Cdd:cd11849      2 YRALYDFKSAEPNTLSFSEGETFLLLERSNAHWWLVTNHSgETGYVPANYV 52

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: 37.73 E-value: 1.48e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755 1066 YRGDEE-TMGFPEGTSLEVLEKNPNgWWYCQVLDglqGRKGWVPSNY 1111
Cdd:cd11837      8 WRAKKEnHLSFAKGDIITVLEQQEM-WWFGELEG---GEEGWFPKSY 50

Uncharacterized conserved protein YgiM, contains N-terminal SH3 domain, DUF1202 family [General function prediction only];

Pssm-ID: 442337 [Multi-domain] Cd Length: 119 Bit Score: 39.72 E-value: 1.52e-03

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 2551499755  271 EKGVTVEVIQKNlEGWWYIRYL-GKEGWAPASYLKK 305
Cdd:COG3103     31 PKGEKVTVLGRS-GGWYKVRYSnGKTGWVSSRYLTV 65

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: 37.44 E-value: 1.75e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLE--GWWYIRYLGKEGWAP 299
Cdd:cd12142      8 YNPVAPDELALKKGDVIEVISKETEdeGWWEGELNGRRGFFP 49

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: 37.48 E-value: 1.88e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  156 AVANYERQENSEISLRAGETVDVIEKSE-SGWWFVSTAEEQGWVPATY 202
Cdd:cd11778      4 ALYDYEAQGDDEISIRVGDRIAVIRGDDgSGWTYGEINGVKGLFPTSY 51

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: 37.65 E-value: 1.91e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  255 ITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11996      4 IAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 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: 37.19 E-value: 1.95e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  455 TIAEFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYI 502
Cdd:pfam07653    4 VIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAV 51

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: 38.07 E-value: 1.99e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755 1069 DEETMGFPEGTSLEVLEKNPNGWWYCQVLDGlqgrKGWVPSNYL 1112
Cdd:cd11973     30 DDQELGFKAGDVIEVMDATNKEWWWGRVLDS----EGWFPASFV 69

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: 37.36 E-value: 2.04e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755 1069 DEETMGFPEGTSLEVLEKNPNGWWycqvlDG-LQGRKGWVPSNYL 1112
Cdd:cd12061     12 NEDELSFSKGDVIHVTRVEEGGWW-----EGtHNGRTGWFPSNYV 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: 37.35 E-value: 2.04e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2551499755 1059 VYVSIADYRGDEE-TMGFPEGTSLEVLEK-----NPNgWWYCQVldglQGRKGWVPSNYLER 1114
Cdd:cd11800      1 YYYALYTFEARSPgELSVTEGQVVTVLEKhdlkgNPE-WWLVED----RGKQGYVPSNYLAK 57

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: 37.27 E-value: 2.06e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  813 LYRTTDAYERAQESELSIPAGVEVEVLEKQESGWWYVRWGV--DEGWVPTFYLEP 865
Cdd:cd11857      1 KYTVVADYEKGGPDDLTVKSGDLVQLIHEGDEGQWLVKNLStrKEGWVPAANLQP 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: 37.38 E-value: 2.22e-03

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 2551499755  467 ISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYI 502
Cdd:cd11975     21 LAFKAGDVIKVLDASNKDWWWGQIDDEEGWFPASFV 56

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: 37.23 E-value: 2.24e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2551499755 1069 DEETMGFPEGTSLEVL-EKNPNGWWYCQVLdglqGRKGWVPSNYLE 1113
Cdd:cd11976     12 DRSELSLKEGDIIKILnKKGQQGWWRGEIY----GRVGWFPANYVE 53

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: 37.04 E-value: 2.27e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIE---KSESGWWFVSTAEEQGWVP 199
Cdd:cd11835      3 HVIKRYTAQAPDELSLEVGDIVSVIDmppPEESTWWRGKKGFQVGFFP 50

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: 37.40 E-value: 2.32e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755 1060 YVSIADYRGDEET-MGFPEGTSLEVLEKNPNGWWYCQVLDglQGRKGWVPSNYL 1112
Cdd:cd12008      2 FVALYDYESRTETdLSFKKGERLQIVNNTEGDWWLAHSLT--TGQTGYIPSNYV 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: 37.29 E-value: 2.38e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWY--IRYLGKEGWAPASYLK 304
Cdd:cd11935      3 YRAMYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYgtVQRTGRTGMLPANYIE 55

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: 37.23 E-value: 2.42e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTA--EEQGWVPAT 201
Cdd:cd11939      1 QVQCVHPYVSQEPDELSLELADVLNILDKTDDGWIFGERLhdQERGWFPSS 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: 37.11 E-value: 2.51e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755  256 TVQPYT-SQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYL 303
Cdd:cd11829      4 TLYAFTgEQHQQGLSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 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: 37.17 E-value: 3.05e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  261 TSQGKDEIGFEKGVTVEVIQKNL---EGWWYIRYLGKEGWAPASYLK 304
Cdd:cd12000     10 KADCSDELAFRRGDILTVLEQNVpgsEGWWKCLLHGRQGLAPANRLQ 56

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: 36.74 E-value: 3.10e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755 1060 YVSIADYRGDEE-TMGFPEGTSLEVLEKNPNGWWYCqvldglqgRK----GWVPSNYLER 1114
Cdd:cd12022      2 YITIKAYTAVEEdELTLLEGEAIEVIHKLLDGWWVV--------RKgevtGYFPSMYLQK 53

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: 36.96 E-value: 3.20e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755 1065 DYRG-DEETMGFPEGTSLEVLEKNPNGWWYCQvldGLQGRKGWVPSNYLER 1114
Cdd:cd11758      8 DFPGnDDEDLPFKKGEILTVIRKPEEQWWNAR---NSEGKTGMIPVPYVEK 55

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: 3.24e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755 1068 GDEetMGFPEGTSLEVLEKNPNG--WWYCqvldGLQGRKGWVPSNYL 1112
Cdd:cd11952     14 PDE--LSFKEGDMVTVLRKDGEGtdWWWA----SLCGREGYVPRNYF 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: 36.63 E-value: 3.25e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESG--WWFVSTAEEQGWVPATYLDA 205
Cdd:cd11842      1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSQndWWTGRIGGREGIFPANYVEL 55

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: 36.50 E-value: 3.54e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKsESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11991      1 EYVAMYTYESNEQGDLTFQQGDVILVTKK-DGDWWTGTVGDKTGVFPSNYV 50

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: 36.53 E-value: 3.60e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  155 VAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd11826      3 VALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNYVE 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: 36.54 E-value: 3.84e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2551499755  155 VAVANYE--RQENSEISLRAGETVDV-IEKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd11978      2 IAIARYDfcARDMRELSLLKGDVVKIyTKMSTNGWWRGEVNGRVGWFPSTYVE 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: 36.72 E-value: 3.84e-03

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2551499755  466 GISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYI 502
Cdd:cd11829     16 GLSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 52

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: 36.57 E-value: 3.89e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755  259 PYTSQGKDEIGFEKGVTVEVIQK-NLEGWWYIR-YLGKEGWAPASYLKK 305
Cdd:cd11761      9 SYEAQRPDELTITEGEELEVIEDgDGDGWVKARnKSGEVGYVPENYLQF 57

Src homology 3 domain of Obscurin and similar proteins; Obscurin is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212958 Cd Length: 63 Bit Score: 36.78 E-value: 3.92e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755  254 YITVQPYTSQG--KDEIGFEKGVTVEVIQKNLEGWWYIR------YLGKEGWAPASYLKK 305
Cdd:cd12025      4 YIVTADYTPDGadTEAIPLEEGQYVEVLDSAHPLKWLVRtkptksSPPRQGWVSPAYLEK 63

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: 36.54 E-value: 3.97e-03

                           10        20
                   ....*....|....*....|....*...
gi 2551499755  820 YERAQESELSIPAGVEVEVLEKQESGWW 847
Cdd:cd11874      8 YTPQNEDELELKVGDTIEVLGEVEEGWW 35

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: 36.56 E-value: 4.02e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNlEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11990      8 WTAKKDNHLNFSKNDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVK 51

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: 36.40 E-value: 4.31e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755 1070 EETMGFPEGTSLEVLEKN---PNGWWYCQvldgLQGRKGWVPSNYLE 1113
Cdd:cd12000     14 SDELAFRRGDILTVLEQNvpgSEGWWKCL----LHGRQGLAPANRLQ 56

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: 36.51 E-value: 4.43e-03

                           10        20        30
                   ....*....|....*....|....*....|....
gi 2551499755  154 YVAVANYERQENSEISLRAGETVDVIEKSESGWW 187
Cdd:cd11925      3 YLALYAYKPQKNDELELRKGEMYRVIEKCQDGWF 36

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: 36.52 E-value: 4.48e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2551499755 1069 DEETMGFPEGTSLEVLEKNPNGWWycqvlDG-LQGRKGWVPSNYLERKK 1116
Cdd:cd12060     14 NEDELSVCKGDIIYVTRVEEGGWW-----EGtLNGKTGWFPSNYVREIK 57

Src homology 3 domain of yeast cell fusion protein Fus1p; Fus1p is required at the cell surface for cell fusion during the mating response in yeast. It requires Bch1p and Bud7p, which are Chs5p-Arf1p binding proteins, for localization to the plasma membrane. It acts as a scaffold protein to assemble a cell surface complex which is involved in septum degradation and inhibition of the NOG pathway to promote cell fusion. The SH3 domain of Fus1p interacts with Bin1p, a formin that controls the assembly of actin cables in response to Cdc42 signaling. It has been shown to bind the motif, R(S/T)(S/T)SL, instead of PxxP motifs. 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: 212788 [Multi-domain] Cd Length: 56 Bit Score: 36.53 E-value: 4.58e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFV----STAEEQGWVPATYLD 204
Cdd:cd11854      1 LMTVISTFEPSLDDELLIKVGETVRVLAEYDDGWCLVeradGLNGDRGMVPGECLQ 56

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: 36.39 E-value: 4.69e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755  151 LEQYVAVANYERQENSEISLRAGETVDVIEKS--ESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd11988      1 LVNYRALYPFEARNHDEMSFNAGDIIQVDEKTvgEPGWLYGSFQGNFGWFPCNYVE 56

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: 36.21 E-value: 4.71e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  458 EFQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDM--EGWAPCSYI 502
Cdd:cd11858      7 DFAGSVANELSLKKDDIVYIVQKEDNGWWLAKKLDEskEGWVPAAYL 53

Uncharacterized conserved protein YgiM, contains N-terminal SH3 domain, DUF1202 family [General function prediction only];

Pssm-ID: 442337 [Multi-domain] Cd Length: 119 Bit Score: 38.18 E-value: 4.75e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755  169 SLRAGETVDVIEKSeSGWWFVSTAEEQ-GWVPATYLDAQTGTRDDLDLGTSrsgevtkrrkahlkrldrrwtlggiVNRQ 247
Cdd:COG3103     29 TLPKGEKVTVLGRS-GGWYKVRYSNGKtGWVSSRYLTVTPSARERLPDELN-------------------------LRAG 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2551499755  248 QSREEKYITVQPytsqgkdeigfeKGVTVEVIQKNlEGWWYIRYlGKEGWA 298
Cdd:COG3103     83 PSTSSEVLGLLP------------KGETVTVLKKS-GGWFKVGY-RGTGWV 119

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: 36.52 E-value: 4.84e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755 1067 RGDEETMGFPEGTSLEVLEKNPN--GWWYCQvldGLQGRKGWVPSNYLER 1114
Cdd:cd11767     10 GENDEELSFEKGERLEIIEKPEDdpDWWKAR---NALGTTGLVPRNYVEV 56

Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (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: 212784 Cd Length: 56 Bit Score: 36.24 E-value: 4.93e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755 1068 GDEETMGFPEGTSLEVLEKNPNGWWyCQVLDGLQGRKGWVPSNY 1111
Cdd:cd11850     11 SGENQLSIKKGEQLRVLGYNKNGEW-CEAESKSTGGQGWVPSNY 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: 36.18 E-value: 4.97e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYL-GKEGWAPASYL 303
Cdd:cd11804      8 FKATAEDELSFKKGSILKVLNMEDDPNWYKAELdGKEGLIPKNYI 52

The phosphoinositide binding Phox Homology domain of Sorting Nexin 21; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

Pssm-ID: 132834 Cd Length: 112 Bit Score: 37.86 E-value: 5.29e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2551499755   20 PSKHYVYLINVTYS---DSTSHIIYRRYSKFFDLQMQLLDKFPIE-GGQKDPKKRIipflpgkilfRRSHVRDVAMKRLR 95
Cdd:cd07301     15 HSKYVLYTIYVIQTgqyDPSPAYISRRYSDFERLHRRLRRLFGGEmAGVSFPRKRL----------RKNFTAETIAKRSR 84

                           90       100
                   ....*....|....*....|....*.
gi 2551499755   96 FIDDYCRALVRLpPQISQSEEVLRFF 121
Cdd:cd07301     85 AFEQFLCHLHSL-PELRASPAFLEFF 109

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: 36.21 E-value: 5.42e-03

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2551499755  827 ELSIPAGVEVEVLEKQESGWWYVRWGVDEGWVPTFYL 863
Cdd:cd11828     15 ELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFV 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: 36.20 E-value: 5.46e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755  459 FQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYI 502
Cdd:cd12061      8 FQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYV 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: 36.24 E-value: 5.49e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  156 AVANYERQENSEISLRAGETVDVI-EKSESGWWFVSTAEEQGWVPATYLD 204
Cdd:cd11843      4 ALYDYEGQESDELSFKAGDILTKLeEEDEQGWCKGRLDGRVGLYPANYVE 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: 36.20 E-value: 5.60e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  812 ALYrttdAYERAQESELSIPAGVEVEVLEK---QESGWWYVRWGVDEGWVPTFYL 863
Cdd:cd11807      5 ALF----DYEAENGDELSFREGDELTVLRKgddDETEWWWARLNDKEGYVPRNLL 55

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: 36.20 E-value: 5.78e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755 1060 YVSIADYRGDEET-MGFPEGTSLEVLEKNPNGWWycqvLDGLQGRKGWVPSNYLE 1113
Cdd:cd11824      2 YSVLYDYTAQEDDeLSISKGDVVAVIEKGEDGWW----TVERNGQKGLVPGTYLE 52

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: 36.14 E-value: 6.10e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2551499755 1070 EETMGFPEGTSLEVLEKNPNGWWYcqvlDGLQGRKGWVPSNYL 1112
Cdd:cd11902     14 EDELSLVKGSRVTVMEKCSDGWWR----GSYNGQIGWFPSNYV 52

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: 35.67 E-value: 6.77e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2551499755  254 YITVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPA 300
Cdd:cd11983      3 FVVVKSYQPQVEGEIPLHKGDRVKVLSIGEGGFWEGSARGHVGWFPA 49

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: 36.04 E-value: 7.04e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIE----KSESGWWFVSTAEEQGWVPATYL 203
Cdd:cd11941      1 QVVAAYPFTARSKHEVSLQAGQPVTVLEphdkKGSPEWSLVEVNGQRGYVPSSYL 55

Uncharacterized conserved protein YgiM, contains N-terminal SH3 domain, DUF1202 family [General function prediction only];

Pssm-ID: 442337 [Multi-domain] Cd Length: 119 Bit Score: 37.80 E-value: 7.13e-03

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2551499755  829 SIPAGVEVEVLEKQeSGWWYVR-WGVDEGWVPTFYLEP 865
Cdd:COG3103     29 TLPKGEKVTVLGRS-GGWYKVRySNGKTGWVSSRYLTV 65

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: 36.00 E-value: 7.45e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2551499755  451 TEYYTIAEFQSCISDGISFRGGQKADVIEKNSG--GWWYVQIGDMEGWAPCSYIDK 504
Cdd:cd11988      2 VNYRALYPFEARNHDEMSFNAGDIIQVDEKTVGepGWLYGSFQGNFGWFPCNYVEK 57

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: 36.03 E-value: 7.57e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2551499755  259 PYTSQGKDEIGFEKGVTVEVIQKNL--EGWWYIRYLGKEGWAPASYLKKL 306
Cdd:cd12057      7 PYEAQNEDELTIKEGDIVTLISKDCidAGWWEGELNGRRGVFPDNFVKLL 56

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: 35.58 E-value: 7.61e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2551499755  260 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 304
Cdd:cd11949      8 FDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVT 52

Fourth (C-terminal) 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 fourth (C-terminal) 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: 212951 Cd Length: 56 Bit Score: 35.64 E-value: 7.84e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2551499755  825 ESELSIPAGVEVEVLEKQESGWWYVRWGVD----EGWVPTFYL 863
Cdd:cd12018     12 EDTSSFKEGTVFEVREKNSSGWWFCKVLSGgpvwEGWIPSNYL 54

Uncharacterized conserved protein YgiM, contains N-terminal SH3 domain, DUF1202 family [General function prediction only];

Pssm-ID: 442337 [Multi-domain] Cd Length: 119 Bit Score: 37.41 E-value: 7.85e-03

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2551499755 1076 PEGTSLEVLEKNpNGWWycQVLDGlQGRKGWVPSNYLE 1113
Cdd:COG3103     31 PKGEKVTVLGRS-GGWY--KVRYS-NGKTGWVSSRYLT 64

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: 36.15 E-value: 8.52e-03

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2551499755  467 ISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYIDKR 505
Cdd:cd11973     34 LGFKAGDVIEVMDATNKEWWWGRVLDSEGWFPASFVRLR 72

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: 35.35 E-value: 9.11e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2551499755  459 FQSCISDGISFRGGQKADVIEKNSGGWWYVQIGDMEGWAPCSYI 502
Cdd:cd11772      8 YEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYV 51

Src Homology 3 domain of SH3 domain and tetratricopeptide repeat-containing (SH3TC) proteins and similar domains; This subfamily is composed of vertebrate SH3TC proteins and hypothetical fungal proteins containing BAR and SH3 domains. Mammals contain two SH3TC proteins, SH3TC1 and SH3TC2. The function of SH3TC1 is unknown. SH3TC2 is localized in Schwann cells in the peripheral nervous system, where it interacts with Rab11 and plays a role in peripheral nerve myelination. Mutations in SH3TC2 are associated with Charcot-Marie-Tooth disease type 4C, a severe hereditary peripheral neuropathy with symptoms that include progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. 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: 212818 Cd Length: 55 Bit Score: 35.37 E-value: 9.20e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVI-EKSESGWWFVSTAE---EQGWVPATY 202
Cdd:cd11885      1 SCTAKMDFEGVEPGELSFRQGDSIEIIgDLIPGLQWFVGRSKssgRVGFVPTNH 54

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: 35.57 E-value: 9.92e-03

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gi 2551499755  153 QYVAVANYERQENSEISLRAGETVDVIEKSESGWWFVSTAEEQGWVPATY 202
Cdd:cd11950      1 QVRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANY 50