SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers, relative to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 112821670  627 QPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 691
Cdd:cd09559     2 QPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 66

Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumor growth, metastasis, and poor prognosis. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 112821670  550 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 606
Cdd:cd11967     1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  693 NSDQSGSQEKLLVDNQGLSGRSPRDSGCYESSENLENAKTHKPSVLSTKSSTESNLKSFTRSQPGNYPTLPlmksgevrk 772
Cdd:PHA03307   39 SQGQLVSDSAELAAVTVVAGAAACDRFEPPTGPPPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPP--------- 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  773 qGEEGRLGRGLAPDTAkSCDVPSVTDLSKNRRSLPVSICRSCETLEGPEPVESWPRSHSldDLQGDADVGKNVPTEMPET 852
Cdd:PHA03307  110 -GPSSPDPPPPTPPPA-SPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGASPAAVASDA--ASSRQAALPLSSPEETARA 185

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  853 CSQNVPEVPQKTSACTSKALPRGRDPTAdvmlltqSKRFSDPPKTMAKKLDGSVVASNLGIAPPQCIPRDFE-------- 924
Cdd:PHA03307  186 PSSPPAEPPPSTPPAAASPRPPRRSSPI-------SASASSPAPAPGRSAADDAGASSSDSSSSESSGCGWGpenecplp 258

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  925 -AQPPVKPGLTRTSLEGLRKGHDHhPLGTKEGVDGEQSAPETRTQSRHPSQPPPVPAKKSRERLANGLHLVPSPEAPilp 1003
Cdd:PHA03307  259 rPAPITLPTRIWEASGWNGPSSRP-GPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSE--- 334

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*....
gi 112821670 1004 lKKASPASPVSPSDCPSPREPRPSSGTEPGSPAcTRPPPWLAELPESTS 1052
Cdd:PHA03307  335 -SSRGAAVSPGPSPSRSPSPSRPPPPADPSSPR-KRPRPSRAPSSPAAS 381

SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers, relative to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 112821670  627 QPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 691
Cdd:cd09559     2 QPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 66

Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumor growth, metastasis, and poor prognosis. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 112821670  550 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 606
Cdd:cd11967     1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57

SAM domain (Sterile alpha motif);

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 112821670  1164 SMSDWLISIGLPMYTSTLSDAGFSTLSQVPSLSHSCLQEAGITEERHIRKLITAARLFK 1222
Cdd:pfam07647    8 SVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  693 NSDQSGSQEKLLVDNQGLSGRSPRDSGCYESSENLENAKTHKPSVLSTKSSTESNLKSFTRSQPGNYPTLPlmksgevrk 772
Cdd:PHA03307   39 SQGQLVSDSAELAAVTVVAGAAACDRFEPPTGPPPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPP--------- 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  773 qGEEGRLGRGLAPDTAkSCDVPSVTDLSKNRRSLPVSICRSCETLEGPEPVESWPRSHSldDLQGDADVGKNVPTEMPET 852
Cdd:PHA03307  110 -GPSSPDPPPPTPPPA-SPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGASPAAVASDA--ASSRQAALPLSSPEETARA 185

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  853 CSQNVPEVPQKTSACTSKALPRGRDPTAdvmlltqSKRFSDPPKTMAKKLDGSVVASNLGIAPPQCIPRDFE-------- 924
Cdd:PHA03307  186 PSSPPAEPPPSTPPAAASPRPPRRSSPI-------SASASSPAPAPGRSAADDAGASSSDSSSSESSGCGWGpenecplp 258

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  925 -AQPPVKPGLTRTSLEGLRKGHDHhPLGTKEGVDGEQSAPETRTQSRHPSQPPPVPAKKSRERLANGLHLVPSPEAPilp 1003
Cdd:PHA03307  259 rPAPITLPTRIWEASGWNGPSSRP-GPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSE--- 334

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*....
gi 112821670 1004 lKKASPASPVSPSDCPSPREPRPSSGTEPGSPAcTRPPPWLAELPESTS 1052
Cdd:PHA03307  335 -SSRGAAVSPGPSPSRSPSPSRPPPPADPSSPR-KRPRPSRAPSSPAAS 381

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 112821670   551 RARVHTDFTPspYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 603
Cdd:pfam07653    1 YGRVIFDYVG--TDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAV 51

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670   842 GKNVPTEMPETC-SQNVPEVPQKTSACTSKaLPRGRDPTADVMLLTQSKRFSDPPKTMAKKldgsvvaSNLGIAPPQCIP 920
Cdd:pfam03154  187 PPPGTTQAATAGpTPSAPSVPPQGSPATSQ-PPNQTQSTAAPHTLIQQTPTLHPQRLPSPH-------PPLQPMTQPPPP 258

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670   921 RDFEAQPPVKPGLTRTSLEG---LRKGHDH--HPLGTKEGVDGEQSA--------------PETRTQSRHPSQPPPVPAK 981
Cdd:pfam03154  259 SQVSPQPLPQPSLHGQMPPMphsLQTGPSHmqHPVPPQPFPLTPQSSqsqvppgpspaapgQSQQRIHTPPSQSQLQSQQ 338

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670   982 KSRERLANGL-----HLVPSPEAPILPLKKA---------SPASPVS-PSDCPSPREPRPSSGTEPGSPACTRPPPwLAE 1046
Cdd:pfam03154  339 PPREQPLPPAplsmpHIKPPPTTPIPQLPNPqshkhpphlSGPSPFQmNSNLPPPPALKPLSSLSTHHPPSAHPPP-LQL 417

                          250       260
                   ....*....|....*....|...
gi 112821670  1047 LPESTSLQEHGVKlGPVLSRKVS 1069
Cdd:pfam03154  418 MPQSQQLPPPPAQ-PPVLTQSQS 439

SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers, relative to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 112821670  627 QPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 691
Cdd:cd09559     2 QPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQEYD 66

Src homology 3 domain of SAM And SH3 Domain Containing Protein 1; SASH1 is a potential tumor suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumor growth, metastasis, and poor prognosis. It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm. SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 112821670  550 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 606
Cdd:cd11967     1 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDVL 57

Src homology 3 domain of Sam And SH3 Domain Containing Protein 3; SASH3, also called SLY/SLY1 (SH3-domain containing protein expressed in lymphocytes), is expressed exclusively in lymhocytes and is essential in the full activation of adaptive immunity. It is involved in the signaling of T cell receptors. It was the first described member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 112821670  550 GRARVHTDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 605
Cdd:cd11968     1 GRARVHTDFIPSPYDGDSLKLQKGDIIQIIEKPPVGTWTGLLNNKVGTFKFIYVDV 56

SAM (Sterile alpha motif ), SASH1-like; SAM (sterile alpha motif) domain of SASH1-like proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. Proteins of this subfamily are known to be involved in preventing DN thymocytes from premature initiation of programmed cell death and in B cells activation and differentiation. They have been found downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  627 QPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVEL 686
Cdd:cd09493     1 KPKTVEELLERINLQEHTSTLLLNGYETLEDFKDLKESHLNELNITDPEHRAKLLTAAEL 60

SAM domain of SAMSN1 subfamily; SAM (sterile alpha motif) domain of SAMSN1 (also known as HACS1 or NASH1) proteins is a predicted protein-protein interaction domain. Members of this group are putative signaling/adaptor proteins. They appear to mediate signal transduction in lymphoid tissues. Murine HACS1 protein likely plays a role in B cell activation and differentiation. Potential binding partners of HACS1 are SLAM, DEC205 and PIR-B receptors and also some unidentified tyrosine-phosphorylated proteins. Proteins of this group were found preferentially expressed in normal hematopietic tissues and in some malignancies including lymphoma, myeloid leukemia and myeloma.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 112821670  624 RPSQPKSVEDLLDRINLKEHMPTFLFNGYEDLDTFKLLEEEDLDELNIRDPEHRAVLLTAVELLQE 689
Cdd:cd09561     1 RRPKPKTLQELLERIHLQEYTSTLLLNGYETLEDLKDLKESHLIELNITDPEDRARLLSAAENLLD 66

SAM domain (Sterile alpha motif);

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 112821670  1164 SMSDWLISIGLPMYTSTLSDAGFSTLSQVPSLSHSCLQEAGITEERHIRKLITAARLFK 1222
Cdd:pfam07647    8 SVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 112821670  551 RARVhtDFTPSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 598
Cdd:cd11874     1 RCKV--LFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVF 46

SAM domain of Ship2 lipid phosphatase proteins; SAM (sterile alpha motif) domain of Ship2 subfamily is a protein-protein interaction domain. Ship2 proteins are lipid phosphatases (Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2) containing an N-terminal SH2 domain, a central phosphatase domain and a C-terminal SAM domain. Ship2 is involved in a number of PI3K signaling pathways. For example, it plays a role in regulation of the actin cytoskeleton remodeling, in insulin signaling pathways, and in EphA2 receptor endocytosis. SAM domain of Ship2 can interact with SAM domain of other proteins in these pathways, thus participating in signal transduction. In particular, SAM of Ship2 is known to form heterodimers with SAM domain of Eph-A2 receptor tyrosine kinase during receptor endocytosis as well as with SAM domain of PI3K effector protein Arap3 in the actin cytoskeleton signaling network. Since Ship2 plays a role in negatively regulating insulin signaling, it has been suggested that inhibition of its expression or function may contribute in treating type 2 diabetes and obesity-induced insulin resistance.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 112821670 1163 ASMSDWLISIGLPMYTSTLSDAGFSTLSQVPSLSHSCLQEAGITEERHIRKLI 1215
Cdd:cd09491     6 KTVSEWLMNLGLQQYEEGLMHNGWDSLEFLSDITEEDLEEAGVTNPAHKRRLL 58

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 112821670  562 PYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVD 604
Cdd:cd11827    10 AQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVE 52

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 112821670  557 DFTPSPYDtdSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 605
Cdd:cd11823     7 SYTANRED--ELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVEE 53

SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B6 receptors and appears to mediate cell-cell initiated signal transduction. Receptors of this type are highly expressed in embryo and adult nervous system, in thymus and also in T-cells. They are involved in regulation of cell adhesion and migration. (EPH-B6 receptor is unusual; it fails to show catalytic activity due to alteration in kinase domain). EPH-B6 may be considered as a biomarker in some types of tumors; EPH-B6 activates MAP kinase signaling in lung adenocarcinoma, suppresses metastasis formation in non-small cell lung cancer, and slows invasiveness in some breast cancer cell lines.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 112821670 1161 CVASMSDWLISIGLPMYTSTLSDAGFSTLSQVPSLSHSCLQEAGITEERHIRKLITAARLFK 1222
Cdd:cd09555     5 CLDSPQAWLSAIGLECYQDNFSKFGLCTFSDVAQLSLEDLPALGITLAGHQKKLLHHIQLLQ 66

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 112821670  551 RARVHTDFTPSpyDTDSLKLKKGDIIDIISK--PPMGTWMGLLNNKVGTF 598
Cdd:cd11875     1 KARVLFDYEAE--NEDELTLREGDIVTILSKdcEDKGWWKGELNGKRGVF 48

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 112821670  564 DTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 603
Cdd:cd11877    12 NEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYV 51

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  693 NSDQSGSQEKLLVDNQGLSGRSPRDSGCYESSENLENAKTHKPSVLSTKSSTESNLKSFTRSQPGNYPTLPlmksgevrk 772
Cdd:PHA03307   39 SQGQLVSDSAELAAVTVVAGAAACDRFEPPTGPPPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPP--------- 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  773 qGEEGRLGRGLAPDTAkSCDVPSVTDLSKNRRSLPVSICRSCETLEGPEPVESWPRSHSldDLQGDADVGKNVPTEMPET 852
Cdd:PHA03307  110 -GPSSPDPPPPTPPPA-SPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGASPAAVASDA--ASSRQAALPLSSPEETARA 185

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  853 CSQNVPEVPQKTSACTSKALPRGRDPTAdvmlltqSKRFSDPPKTMAKKLDGSVVASNLGIAPPQCIPRDFE-------- 924
Cdd:PHA03307  186 PSSPPAEPPPSTPPAAASPRPPRRSSPI-------SASASSPAPAPGRSAADDAGASSSDSSSSESSGCGWGpenecplp 258

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  925 -AQPPVKPGLTRTSLEGLRKGHDHhPLGTKEGVDGEQSAPETRTQSRHPSQPPPVPAKKSRERLANGLHLVPSPEAPilp 1003
Cdd:PHA03307  259 rPAPITLPTRIWEASGWNGPSSRP-GPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSE--- 334

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*....
gi 112821670 1004 lKKASPASPVSPSDCPSPREPRPSSGTEPGSPAcTRPPPWLAELPESTS 1052
Cdd:PHA03307  335 -SSRGAAVSPGPSPSRSPSPSRPPPPADPSSPR-KRPRPSRAPSSPAAS 381

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 112821670  551 RARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYV 603
Cdd:cd11805     1 RVQALYDFNPQ--EPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYV 51

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  846 PTEMPETCSQNVPEVPQKTSACTSKALPRGRDPTAdvmlltqskrfSDPPKTMAKKLDGSVVASNLGIAPPQCIPRDFEA 925
Cdd:PHA03247 2589 PDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHA-----------PDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPA 2657

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  926 QPPVKPGlTRTSLEGLRKGHDHHPLGTKEGVDGEQSAPETRTQSRHPSQPPPVPA-------------KKSRERLANGLH 992
Cdd:PHA03247 2658 PGRVSRP-RRARRLGRAAQASSPPQRPRRRAARPTVGSLTSLADPPPPPPTPEPAphalvsatplppgPAAARQASPALP 2736

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 112821670  993 LVP----SPEAPILPLKKASPASPVSPSDCPSPREPRpssgTEPGSPACTRPPPWLAELPEST 1051
Cdd:PHA03247 2737 AAPappaVPAGPATPGGPARPARPPTTAGPPAPAPPA----APAAGPPRRLTRPAVASLSESR 2795

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 112821670  551 RARVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGT--WMGLLNNKVGTFKFIYVDV 605
Cdd:cd11842     1 KAVALYDFAGE--QPGDLAFQKGDIITILKKSDSQNdwWTGRIGGREGIFPANYVEL 55

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 112821670  553 RVHTDFTPSpyDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFK 599
Cdd:cd11883     3 VALYDFTPK--SKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKVK 47

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.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 112821670  566 DSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVD 604
Cdd:cd11766    14 DELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYVT 52

SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 112821670 1162 VASMSDWLISIGLPMYTSTLSDAGFSTLSQVPSLSHSCLQEAGITEERHIRKLITAARLFKL 1223
Cdd:cd09547     3 FVTVSDWLDSIKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIGHQRRIVSSIQTLRL 64

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 112821670  562 PYDT---DSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTF 598
Cdd:cd11873     7 DYDAeepDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMF 46

SAM (Sterile alpha motif ), SASH1-like; SAM (sterile alpha motif) domain of SASH1-like proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. Proteins of this subfamily are known to be involved in preventing DN thymocytes from premature initiation of programmed cell death and in B cells activation and differentiation. They have been found downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 112821670 1164 SMSDWLISIGLPMYTSTLSDAGFSTLSQVPSLSHSCLQEAGITEERHIRKLITAARL 1220
Cdd:cd09493     4 TVEELLERINLQEHTSTLLLNGYETLEDFKDLKESHLNELNITDPEHRAKLLTAAEL 60

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 112821670  562 PYDT---DSLKLKKGDIIDIISKP--PMGTWMGLLNNKVGTFKFIYVDVL 606
Cdd:cd12057     7 PYEAqneDELTIKEGDIVTLISKDciDAGWWEGELNGRRGVFPDNFVKLL 56

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  908 ASNLGIAPPQCIPRDFE-------AQPPVKPGLTRTSLEGLRKGHDHHPlgtkegvdgeqSAPETRTQSRHPSQPPPvPA 980
Cdd:PHA03247 2563 APDRSVPPPRPAPRPSEpavtsraRRPDAPPQSARPRAPVDDRGDPRGP-----------APPSPLPPDTHAPDPPP-PS 2630

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112821670  981 KKSRERLANGLHLVPSPEAPILPL--------------KKASPASPVSPSDCPSPREPRPSSGT--------EPGSPACT 1038
Cdd:PHA03247 2631 PSPAANEPDPHPPPTVPPPERPRDdpapgrvsrprrarRLGRAAQASSPPQRPRRRAARPTVGSltsladppPPPPTPEP 2710

                         170
                  ....*....|....*....
gi 112821670 1039 RPPPWLAELPESTSLQEHG 1057
Cdd:PHA03247 2711 APHALVSATPLPPGPAAAR 2729

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 112821670 1162 VASMSDWLISIGLPMYTSTLSDAGFSTLSQVPSLSHSCLQEAGITEERHIRKLI 1215
Cdd:cd09490     3 DLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRIL 56

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
                  ....*....|....*....|....*....|..
gi 112821670  628 PKSVEDLLDRINLKEHMPTFLFNGYEDLDTFK 659
Cdd:cd09500     5 PASVSEWLDSIGLGDYIETFLKHGYTSMERVK 36

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 112821670  551 RARVHTDFtpSPYDTDSLKLKKGDIIDIISKPPMGTWMGLLNNKVGTFKFIYVDV 605
Cdd:cd11813     1 RAKALLDF--ERHDDDELGFRKNDIITIISQKDEHCWVGELNGLRGWFPAKFVEL 53