Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 626 QYWQHHPEKLIFQSCDYKAFYLGSMLIKELRGTESTQDACAKMRancqKSTEQMKKVPTIILSVSYKGVKFIDATNKNII 705
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLK----KSTREMKKIPTIILSISYKGVKFIDATTKNLI 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 706 AEHEIRNISCAAQDPEDLSTFAYITKDLKSNHHYCHVFTAFDVNLAYEIILTLGQAFEVAYQLALQARKG 775
Cdd:cd01274    77 CEHEIRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370462393 462 DGYHPTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVELINVLKINLIGHRKRILASLGDR 526
Cdd:cd09500     1 DGNSPASVSEWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTNVLEINKLGHRKRILASLADR 65

Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 626 QYWQHHPEKLIFQSCDYKAFYLGSMLIKELRGTESTQDACAKMRancqKSTEQMKKVPTIILSVSYKGVKFIDATNKNII 705
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLK----KSTREMKKIPTIILSISYKGVKFIDATTKNLI 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 706 AEHEIRNISCAAQDPEDLSTFAYITKDLKSNHHYCHVFTAFDVNLAYEIILTLGQAFEVAYQLALQARKG 775
Cdd:cd01274    77 CEHEIRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370462393 462 DGYHPTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVELINVLKINLIGHRKRILASLGDR 526
Cdd:cd09500     1 DGNSPASVSEWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTNVLEINKLGHRKRILASLADR 65

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370462393  388 PRCPVQTVGQWLESIGLPQYENHLMANGFDNVQFMgsNVMEDQDLLEIGILNSGHRQRILQAIQLL 453
Cdd:smart00454   2 SQWSPESVADWLESIGLEQYADNFRKNGIDGALLL--LLTSEEDLKELGITKLGHRKKILKAIQKL 65

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370462393 462 DGYHPTSVAEWLDSIELGDYTKAFLiNGYTSMDLLKKIWEVELINvLKINLIGHRKRILASL 523
Cdd:pfam00536   1 DGWSVEDVGEWLESIGLGQYIDSFR-AGYIDGDALLQLTEDDLLK-LGVTLLGHRKKILYAI 60

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370462393  462 DGYHPTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEvELINVLKINLIGHRKRILASL 523
Cdd:smart00454   2 SQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSE-EDLKELGITKLGHRKKILKAI 62

Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 626 QYWQHHPEKLIFQSCDYKAFYLGSMLIKELRGTESTQDACAKMRancqKSTEQMKKVPTIILSVSYKGVKFIDATNKNII 705
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLK----KSTREMKKIPTIILSISYKGVKFIDATTKNLI 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 706 AEHEIRNISCAAQDPEDLSTFAYITKDLKSNHHYCHVFTAFDVNLAYEIILTLGQAFEVAYQLALQARKG 775
Cdd:cd01274    77 CEHEIRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370462393 462 DGYHPTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVELINVLKINLIGHRKRILASLGDR 526
Cdd:cd09500     1 DGNSPASVSEWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTNVLEINKLGHRKRILASLADR 65

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 642 YKAFYLGSMLIKELRGTESTQDACAKMRANCQKSTEQMKKVptiILSVSYKGVKFIDATNKNIIAEHEIRNISCAAQDPE 721
Cdd:cd00934     3 FQVKYLGSVEVGSSRGVDVVEEALKALAAALKSSKRKPGPV---LLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPD 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1370462393 722 DLSTFAYITKDLKSNHHYCHVFTAFDVNLAYEIILTLGQAF 762
Cdd:cd00934    80 NPNVFAFIAGEEGGSGFRCHVFQCEDEEEAEEILQAIGQAF 120

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370462393  388 PRCPVQTVGQWLESIGLPQYENHLMANGFDNVQFMgsNVMEDQDLLEIGILNSGHRQRILQAIQLL 453
Cdd:smart00454   2 SQWSPESVADWLESIGLEQYADNFRKNGIDGALLL--LLTSEEDLKELGITKLGHRKKILKAIQKL 65

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370462393 391 PVQTVGQWLESIGLPQYENHLMAnGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQLL 453
Cdd:pfam00536   4 SVEDVGEWLESIGLGQYIDSFRA-GYIDGDALLQ--LTEDDLLKLGVTLLGHRKKILYAIQRL 63

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 642 YKAFYLGSMLIKELR------GTESTQDA--CAKMRANCQKSTEQMKKVP--TIILSVSYKGVKFIDATNKNIIAEHEIR 711
Cdd:pfam00640   1 FAVRYLGSVEVPEERapdkntRMQQAREAirRVKAAKINKIRGLSGETGPgtKVDLFISTDGLKLLNPDTQELIHDHPLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370462393 712 NIS-CAAQDPEDLSTFAYITKDLKSNHHYCHVFTAFDvnLAYEIILTLGQAFEVA 765
Cdd:pfam00640  81 SISfCADGDPDLMRYFAYIARDKATNKFACHVFESED--GAQDIAQSIGQAFALA 133

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370462393  462 DGYHPTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEvELINVLKINLIGHRKRILASL 523
Cdd:smart00454   2 SQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSE-EDLKELGITKLGHRKKILKAI 62

Shc-like phosphotyrosine-binding (PTB) domain; Shc is a substrate for receptor tyrosine kinases, which can interact with phosphoproteins at NPXY motifs. Shc contains an PTB domain followed by an SH2 domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Shc-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 684 TIILSVSYKGVKFIDATNKNIIAEHEIRNISCAA-QDPEDLSTFAYITKDlKSNHHYCHVFTAFDvNLAYEIILTLGQAF 762
Cdd:cd01209    84 NISLTISTDGLNLVTPDTGQIIANHHMQSISFASgGDPDTYDYVAYVAKD-PVNQRACHVLECGD-GLAQDVIATIGQAF 161

                  ....*....
gi 1370462393 763 EVAYQLALQ 771
Cdd:cd01209   162 ELRFKQYLK 170

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370462393 395 VGQWLESIGLPQYENHLMANGFDNVQFMgsnVMEDQDLLEIGILNSGHRQRILQAIQ 451
Cdd:cd09487     2 VAEWLESLGLEQYADLFRKNEIDGDALL---LLTDEDLKELGITSPGHRKKILRAIQ 55

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370462393 468 SVAEWLDSIELGDYTKAFLINGYTSMDLLKKIwEVELINVLKINLIGHRKRILASL 523
Cdd:cd09546     5 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQV-TLEDLRRLGVTLVGHQKKIMNSI 59

Disabled (Dab) Phosphotyrosine-binding domain; Dab is a cystosolic adaptor protein, which binds to the cytoplasmic tails of lipoprotein receptors, such as ApoER2 and VLDLR, via its PTB domain. The dab PTB domain has a preference for unphosphorylated tyrosine within an NPxY motif. Additionally, the Dab PTB domain, which is structurally similar to PH domains, binds to phosphatidlyinositol phosphate 4,5 bisphosphate in a manner characteristic of phosphoinositide binding PH domains. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 641 DYKAFYLGSMLIKELRGTESTQDACAKMRaNCQKSTEQMKKvpTIILSVSYKGVKFIDATNKNIIAEHEIRNISCAAQDP 720
Cdd:cd01215    17 RFKAKLIGIDEVPAARGDKMCQDAMMKLK-GAVKAAGEHKQ--RIWLNISLEGIKILDEKTGALLHHHPVHKISFIARDT 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1370462393 721 EDLSTFAYITKdLKSNHHYCHVFTAfdvNLAYEIILTLGQAFEVAYQL 768
Cdd:cd01215    94 TDNRAFGYVCG-LDGGHRFFAIKTA---KAAEPVVLDLRDLFQVVFEL 137

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370462393 391 PVQTVGQWLESIGLPQYENHLMANGFDNvqfMGSNV-MEDQDLLEIGILNSGHRQRILQAIQLL 453
Cdd:cd09488     1 AFRSVGEWLESIKMGRYKENFTAAGYTS---LDAVAqMTAEDLTRLGVTLVGHQKKILNSIQAL 61

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370462393 468 SVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVELINvLKINLIGHRKRILASL 523
Cdd:cd09554     5 SVGEWLRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLR-MGVTLAGHQKKILSSI 59

Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal function, muscle regeneration, and cell migration. It binds to actin filaments and interacts with the cytoplasmic tails of beta-integrin via its PTB domain, allowing tensin to link actin filaments to integrin receptors. Tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins. In addition to its PTB domain, it contains a C-terminal SH2 domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 642 YKAFYLGSMLIKELRGTESTQdacakmraNCQKSTEQMKKVPT----IILSVSYKGVKFIDATNKNIIAEHEIRNISCAA 717
Cdd:cd13157     4 RNAQYIGSFPVSGLDVADRAD--------SVRKQLESLKESGSrgrpVILSVSLSGIKICSEDGKVVLMAHALRRVSYST 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370462393 718 QDPEDlSTFAYITKDLKS--NHHYCHVFTAFDVNLAYEIILTLGQAFEVAY 766
Cdd:cd13157    76 CRPAH-AQFAFVARNPGGptNRQYCHVFVTRSPREAQELNLLLCRAFQLAY 125

SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A8 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A8 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A8 receptors are involved in ligand dependent (ephirin A2, A3, A5) regulation of cell adhesion and migration, and in ligand independent regulation of neurite outgrowth in neuronal cells. They perform signaling in kinase dependent and kinase independent manner. EPH-A8 receptors are known to interact with a number of different proteins including PI 3-kinase and AIDA1-like subfamily SAM repeat domain containing proteins. However other domains (not SAM) of EPH-A8 receptors are involved in these interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370462393 468 SVAEWLDSIELGDYTKAFLINGYTSMDLLKKIwEVELINVLKINLIGHRKRILASL 523
Cdd:cd09550     4 SVDDWLDSIKMGRYKDHFAAGGYSSLGMVMRM-NIEDIRRLGITLMGHQKKILTSI 58

SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a putative protein-protein interaction domain. Proteins of this subfamily have a SAM domain at the N-terminus. SAM is a widespread domain in signaling and regulatory proteins. In many cases SAM mediates dimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 394 TVGQWLESIGLPQYENHLMANGFDNVQFmgSNVMEDQDLLEIGILNSGHRQRILQAIQLL 453
Cdd:cd09527     4 IVYDWLRTLQLEQYAEKFVDNGYDDLEV--CKQIGDPDLDAIGVMNPAHRKRILEAVRRL 61

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370462393 394 TVGQWLESIGLPQYENHLMANGFDNVQFMGSNVMEdqDLLEIGILNSGHRQRILQAI 450
Cdd:cd09498     9 DLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLTWE--DLQDIGITKLGHQKKLMLAI 63

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370462393 463 GYHPTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKI-WEvELiNVLKINLIGHRKRIL 520
Cdd:cd09498     4 DYPPNDLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLtWE-DL-QDIGITKLGHQKKLM 60

SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B3 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B3 receptor protein kinase performs kinase-dependent and kinase-independent functions. It is known to be involved in thymus morphogenesis, in regulation of cell adhesion and migration. Also EphB3 controls cell positioning and ordered migration in the intestinal epithelium and plays a role in the regulation of adult retinal ganglion cell axon plasticity after optic nerve injury. In some experimental models overexpression of EphB3 enhances cell/cell contacts and suppresses colon tumor growth.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370462393 394 TVGQWLESIGLPQYENHLMANGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQ 451
Cdd:cd09553     8 TVGDWLDAIKMGRYKENFVSAGFASFDLVAQ--MTAEDLLRIGVTLAGHQKKILSSIQ 63

SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a putative protein-protein interaction domain. Proteins of this subfamily have a SAM domain at the N-terminus. SAM is a widespread domain in signaling and regulatory proteins. In many cases SAM mediates dimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370462393 466 PTSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVELInVLKINLIGHRKRIL 520
Cdd:cd09527     2 SNIVYDWLRTLQLEQYAEKFVDNGYDDLEVCKQIGDPDLD-AIGVMNPAHRKRIL 55

SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B2 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B2 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of this subfamily form homodimers/oligomers (in head-to-head/tail-to-tail orientation); apparently such clustering is necessary for signaling. EPH-B2 receptor is involved in regulation of synaptic function; it is needed for normal vestibular function, proper formation of anterior commissure, control of cell positioning, and ordered migration in the intestinal epithelium. EPH-B2 plays a tumor suppressor role in colorectal cancer. It was found to be downregulated in gastric cancer and thus may be a negative biomarker for it.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370462393 467 TSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIwEVELINVLKINLIGHRKRILASL 523
Cdd:cd09552     7 STVDEWLDAIKMGQYKESFANAGFTSFDVVSQM-TMEDILRVGVTLAGHQKKILNSI 62

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370462393 467 TSVAEWLDSIELGDYTKAFLINGYTSMDLLKKIWEVELiNVLKINLIGHRKRILASL 523
Cdd:cd09490     4 LDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRL-KQIGISPTGHRRRILKQL 59

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370462393 391 PVQTVGQWLESIGLPQYENHLMANGFDNVQ-FMGSNvmeDQDLLEIGILNSGHRQRILQAIQ 451
Cdd:cd09490     2 ADLDIAEWLASIHLEQYLDLFREHGYVTATdCQGIN---DSRLKQIGISPTGHRRRILKQLP 60

SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A1 subfamily of the receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A1 receptors and appears to mediate cell-cell initiated signal transduction. Activation of these receptors leads to inhibition of cell spreading and migration in a RhoA-ROCK-dependent manner. EPH-A1 receptors are known to bind ILK (integrin-linked kinase) which is the mediator of interactions between integrin and the actin cytoskeleton. However SAM is not sufficient for this interaction; it rather plays an ancillary role. SAM domains of Eph-A1 receptors do not form homo/hetero dimers/oligomers. EphA1 gene was found expressed widely in differentiated epithelial cells. In a number of different malignant tumors EphA1 genes are downregulated. In breast carcinoma the downregulation is associated with invasive behavior of the cell.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370462393 391 PVQTVGQWLESIGLPQYENHLMANGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQ 451
Cdd:cd09542     3 PYRSVSEWLESIRMKRYILHFRSAGLDTMECVLE--LTAEDLTQMGITLPGHQKRILCSIQ 61

SAM domain of diacylglycerol kinase delta and eta subunits; SAM (sterile alpha motif) domain of DGK-eta-delta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases with a SAM domain located at the C-terminus. DGK proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. The SAM domain of DGK proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers between the SAM domains of DGK delta and eta proteins. The oligomerization plays a role in the regulation of DGK intracellular localization.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370462393 392 VQTVGQWLESIGLPQYENHLMANGFDNVQFMGsnvMEDQDLLEIGILNSGHRQRILQAIQLL 453
Cdd:cd09507     7 TEEVGAWLESLQLGEYRDIFARNDIRGSELLH---LERRDLKDLGITKVGHVKRILQAIKDL 65

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370462393 468 SVAEWLDSIELGDYTKAFLINgYTSMDLLKKIWEVELINvLKINLIGHRKRILASL 523
Cdd:cd09487     1 DVAEWLESLGLEQYADLFRKN-EIDGDALLLLTDEDLKE-LGITSPGHRKKILRAI 54

SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A8 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A8 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A8 receptors are involved in ligand dependent (ephirin A2, A3, A5) regulation of cell adhesion and migration, and in ligand independent regulation of neurite outgrowth in neuronal cells. They perform signaling in kinase dependent and kinase independent manner. EPH-A8 receptors are known to interact with a number of different proteins including PI 3-kinase and AIDA1-like subfamily SAM repeat domain containing proteins. However other domains (not SAM) of EPH-A8 receptors are involved in these interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 394 TVGQWLESIGLPQYENHLMANGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQLL 453
Cdd:cd09550     4 SVDDWLDSIKMGRYKDHFAAGGYSSLGMVMR--MNIEDIRRLGITLMGHQKKILTSIQVM 61

SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A7 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A7 receptors and appears to mediate cell-cell initiated signal transduction. EphA7 was found expressed in human embryonic stem (ES) cells, neural tissues, kidney vasculature. EphA7 knockout mice show decrease in cortical progenitor cell death at mid-neurogenesis and significant increase in cortical size. EphA7 may be involved in the pathogenesis and development of different cancers; in particular, EphA7 was found upregulated in glioblastoma and downregulated in colorectal cancer and gastric cancer. Thus, it is a potential molecular marker and/or therapy target for these types of cancers.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370462393 394 TVGQWLESIGLPQYENHLMANGFDNVQFMGSnvMEDQDLLEIGILNSGHRQRILQAIQ 451
Cdd:cd09548     9 SVGEWLEAIKMERYKDNFTAAGYNSLESVAR--MTIEDVMSLGITLVGHQKKIMSSIQ 64

SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM1 domain has a potential phosphorylation site for CMGC group of serine/threonine kinases. SAM domains of the AIDA1-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370462393 466 PTSVAEWLDSIELGDYTKAFLINGYTSMDLLKK--IWEVELINVlKINLIGHRKRIL 520
Cdd:cd09499     2 VQSVGQWLESIGLPQYESKLLLNGFDDVDFLGSgvMEDQDLKEI-GITDEQHRQIIL 57

GTPase activating protein for Rab 6 Phosphotyrosine-binding (PTB) domain; GAPCenA is a centrosome-associated GTPase activating protein (GAP) for Rab 6. It consists of an N-terminal PTB domain and a C-terminal TBC domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370462393 646 YLGSMLIKELRGTESTQDACAKMRANCQKSTEqmkkvptIILSV--SYKG-VKFIDATNKNIIAEHEIRNIS-CA--AQD 719
Cdd:cd01211     8 YLGCAKVNAPRSETEALRIMAILREQSAQPIK-------VTLSVpnSSEGsVRLYDPTSNTEIASYPIYRILfCArgPDG 80

                          90       100
                  ....*....|....*....|....
gi 1370462393 720 PEDLSTFAYITKDLKSNHHYCHVF 743
Cdd:cd01211    81 TSESDCFAFTWSHGETAIFQCHVF 104

SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 family proteins is a protein-protein interaction domain. Shank1,2,3 proteins are scaffold proteins that are known to interact with a variety of cytoplasmic and membrane proteins. SAM domains of the Shank1,2,3 family are prone to homooligomerization. They are highly enriched in the postsynaptic density, acting as scaffolds to organize assembly of postsynaptic proteins. SAM domains of Shank3 proteins can form large sheets of helical fibers. Shank genes show distinct patterns of expression, in rat Shank1 mRNA is found almost exclusively in brain, Shank2 in brain, kidney and liver, and Shank3 in heart, brain and spleen.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370462393 392 VQTVGQWLESIGLPQYENHLMANGFDnvqfmGSNV--MEDQDLLEIGILNSGHRQRILQAIQLL 453
Cdd:cd09506     7 VDDVGDWLESLNLGEHRERFMDNEID-----GSHLpnLDKEDLTELGVTRVGHRMNIERALKKL 65