Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927372    809 FSEKPISQSLLADLGNEESKYAVETFHAIMKFMGDEPLKKSESMTDVVFKVLLICHRQPTLRDEVYCQLIKQTTSNISQk 888
Cdd:smart00139    1 YTKDPIKTSLLKLESDELQKEAVKIFKAILKFMGDIPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIKQLTDNPSR- 79

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392927372    889 pNSALRAWRLLTIITAYFPSSLTLKPYVLQYLGDNADEWQrpFHGTARICQTNMIQTFKYGGRKVLLNALEVQQIT 964
Cdd:smart00139   80 -QSEERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGS--EQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 392927372  683 FVRALEDYVTSEVNHLSFKQGDVIELLQEpegETPPVGNWLYGKIENRFGFLLAQYV 739
Cdd:cd11884     1 YVVAVRAYITRDQTLLSFHKGDVIKLLPK---EGPLDPGWLFGTLDGRSGAFPKEYV 54

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927372    809 FSEKPISQSLLADLGNEESKYAVETFHAIMKFMGDEPLKKSESMTDVVFKVLLICHRQPTLRDEVYCQLIKQTTSNISQk 888
Cdd:smart00139    1 YTKDPIKTSLLKLESDELQKEAVKIFKAILKFMGDIPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIKQLTDNPSR- 79

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392927372    889 pNSALRAWRLLTIITAYFPSSLTLKPYVLQYLGDNADEWQrpFHGTARICQTNMIQTFKYGGRKVLLNALEVQQIT 964
Cdd:smart00139   80 -QSEERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGS--EQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927372    971 RQAFYISKDHNVSQTLRPITVAEEMIQELCNLLNVRslhEQQEFSLCYTVGKDKHLNYCKNDNYLMDIITESEhkklPFQ 1050
Cdd:smart00295    1 VLKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIR---ESEYFGLQFEDPDEDLRHWLDPAKTLLDQDVKSE----PLT 73

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927372   1051 FYLKRTVWVHP---LRYDNAAYIdSMFDQVIDDYLRGSLIstnslgqltaATTEEIIKLAAYLF-LLLPDNPKGL----N 1122
Cdd:smart00295   74 LYFRVKFYPPDpnqLKEDPTRLN-LLYLQVRNDILEGRLP----------CPEEEALLLAALALqAEFGDYDEELhdlrG 142

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392927372   1123 AKTLPQIVPKSVIepKHRHQEEMVTRISRQLKMFGGrMRPAEAKSHFLELLSTWPTFGVLHY 1184
Cdd:smart00295  143 ELSLKRFLPKQLL--DSRKLKEWRERIVELHKELIG-LSPEEAKLKYLELARKLPTYGVELF 201

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

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 392927372    680 KRKFVRALEDYVTSEVNHLSFKQGDVIELLQEPEgetppvGNWLYGKIEN-RFGFLLAQYV 739
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSD------DGWWKGRLGRgKEGLFPSNYV 55

FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927372 1073 MFDQVIDDYLRGSListnslgqltAATTEEIIKLAAYLFL-LLPDNPKGLNAKT---LPQIVPKSVIepKHRHQEEMVTR 1148
Cdd:cd14473     5 LYLQVKRDILEGRL----------PCSEETAALLAALALQaEYGDYDPSEHKPKylsLKRFLPKQLL--KQRKPEEWEKR 72

                          90       100
                  ....*....|....*....|....*...
gi 392927372 1149 ISRQLKMFGGrMRPAEAKSHFLELLSTW 1176
Cdd:cd14473    73 IVELHKKLRG-LSPAEAKLKYLKIARKL 99

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 392927372   685 RALEDYVTSEVNHLSFKQGDVIELLQEPEGEtppvgnWLYGK-IENRFGF 733
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDG------WWKGRnKGGKEGL 44

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927372    809 FSEKPISQSLLADLGNEESKYAVETFHAIMKFMGDEPLKKSESMTDVVFKVLLICHRQPTLRDEVYCQLIKQTTSNISQk 888
Cdd:smart00139    1 YTKDPIKTSLLKLESDELQKEAVKIFKAILKFMGDIPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIKQLTDNPSR- 79

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392927372    889 pNSALRAWRLLTIITAYFPSSLTLKPYVLQYLGDNADEWQrpFHGTARICQTNMIQTFKYGGRKVLLNALEVQQIT 964
Cdd:smart00139   80 -QSEERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGS--EQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927372    971 RQAFYISKDHNVSQTLRPITVAEEMIQELCNLLNVRslhEQQEFSLCYTVGKDKHLNYCKNDNYLMDIITESEhkklPFQ 1050
Cdd:smart00295    1 VLKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIR---ESEYFGLQFEDPDEDLRHWLDPAKTLLDQDVKSE----PLT 73

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927372   1051 FYLKRTVWVHP---LRYDNAAYIdSMFDQVIDDYLRGSLIstnslgqltaATTEEIIKLAAYLF-LLLPDNPKGL----N 1122
Cdd:smart00295   74 LYFRVKFYPPDpnqLKEDPTRLN-LLYLQVRNDILEGRLP----------CPEEEALLLAALALqAEFGDYDEELhdlrG 142

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392927372   1123 AKTLPQIVPKSVIepKHRHQEEMVTRISRQLKMFGGrMRPAEAKSHFLELLSTWPTFGVLHY 1184
Cdd:smart00295  143 ELSLKRFLPKQLL--DSRKLKEWRERIVELHKELIG-LSPEEAKLKYLELARKLPTYGVELF 201

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

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 392927372    680 KRKFVRALEDYVTSEVNHLSFKQGDVIELLQEPEgetppvGNWLYGKIEN-RFGFLLAQYV 739
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSD------DGWWKGRLGRgKEGLFPSNYV 55

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 392927372  683 FVRALEDYVTSEVNHLSFKQGDVIELLQEPEGEtppvgNWLYGKIENRFGFLLAQYVD 740
Cdd:cd11843     1 PVRALYDYEGQESDELSFKAGDILTKLEEEDEQ-----GWCKGRLDGRVGLYPANYVE 53

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 392927372  683 FVRALEDYVTSEVNHLSFKQGDVIELLQEPEgetppvGNWLYGKIENRFGFLLAQYV 739
Cdd:cd11805     1 RVQALYDFNPQEPGELEFRRGDIITVLDSSD------PDWWKGELRGRVGIFPANYV 51

FERM domain C-lobe of Myosin XV (MyoXV/Myo15); MyoXV, a MyTH-FERM myosin, are actin-based motor proteins essential for a variety of biological processes in actin cytoskeleton function. Specifically MyoXV functions in the actin organization in hair cells of the organ of Corti. Mutations in Human MyoXVa causes non-syndromic deafness, DFNB3 and the mouse shaker-2 mutation. MyoXV consists of a N-terminal motor/head region, a neck made of 1-3 IQ motifs, and a tail that consists of either a myosin tail homology 4 (MyTH4) domains, followed by an SH3 domain, and a MyTH-FERM domains as in rat Myo15 or two MyTH-FERM domains separated by a SH3 domain as in human Myo15A. The MyTH-FERM domains are thought to mediate dimerization and binding to other proteins or cargo. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392927372 1198 EVILTINKSGIQLLQPKSKEVFKERNYDQIVSVESIRKTAYKIVRLVI---NTMQgEETLDIKTDEADEISHLIGQYM 1272
Cdd:cd13201    18 PCLLALNREGLHFLDPKTHETLLRIPLKEVQSTRKLRPLEDGTPFLDIkygNLMQ-QRTIRLETDQAHEISRLIAQYI 94

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 392927372  683 FVRALEDYVTSEVNHLSFKQGDVIELLQEPEgetppvGNWLYGKIENRFGFLLAQYV 739
Cdd:cd11828     1 LAEALWDHVTMDPEELGFKAGDVIEVLDMSD------KDWWWGSIRDEEGWFPASFV 51

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 392927372  684 VRALEDYVTSEVNHLSFKQGDVIELLQePEgetpPVGNWLYGKIE--NRFGFLLAQYV 739
Cdd:cd11779     3 VKALYPHAAGGETQLSFEEGDVITLLG-PE----PRDGWHYGENErsGRRGWFPIAYT 55

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392927372  682 KFVRALEDYVTSEVNHLSFKQGDVIELLQE-PEGetppvgnWLYGKIE--NRFGFLLAQYVDS 741
Cdd:cd11933     2 KSFRAMYDYRAADDDEVSFKDGDTIVNVQTiDEG-------WMYGTVQrtGKTGMLPANYVEA 57

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
                  ....*....|....*....|....*..
gi 392927372  683 FVRALEDYVTSEVNHLSFKQGDVIELL 709
Cdd:cd11883     1 VVVALYDFTPKSKNQLSFKAGDIIYVL 27

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 392927372  686 ALEDYVTSEVNHLSFKQGDVIELLQEPEGETPPVGnWLYGKIENRFGFLLAQYV 739
Cdd:cd12058     4 ALYDYEASGEDELSLRRGDVVEVLSQDAAVSGDDG-WWAGKIRHRLGIFPANYV 56

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 392927372  684 VRALEDYVTSEVNHLSFKQGDVIELLQEPEGETppvgNWLYGKIENRFGFLLAQYVD 740
Cdd:cd11842     2 AVALYDFAGEQPGDLAFQKGDIITILKKSDSQN----DWWTGRIGGREGIFPANYVE 54

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 392927372   683 FVRALEDYVTSEVNHLSFKQGDVIELLQEPEgetppvGNWLYGKIENRFGFLLAQYV 739
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKDN------DGWWEGETGGRVGLVPSTAV 51

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 392927372  685 RALEDYVTSEVNHLSFKQGDVIELLQepegetPPVGNWLYGKIE--NRFGFLLAQYVD 740
Cdd:cd11935     4 RAMYDYSAQDEDEVSFRDGDYIVNVQ------PIDEGWMYGTVQrtGRTGMLPANYIE 55

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

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gi 392927372  686 ALEDYVTSEVNHLSFKQGDVIELLQEPEGetppvgNWLYGKIENRFGFLLAQYV 739
Cdd:cd11833     4 ALYKFKPQENEDLEMRPGDKITLLDDSNE------DWWKGKIEDRVGFFPANFV 51

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

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gi 392927372  685 RALEDYVTSEVNHLSFKQGDVIELLQEPEGetppvgNWLYGKIENRFGFLLAQYVD 740
Cdd:cd11782     3 RAKYNFNADTGVELSFRKGDVITLTRRVDE------NWYEGRIGGRQGIFPVSYVQ 52

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

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gi 392927372  684 VRALEDYVTSEVNHLSFKQGDVIELLQEPEgetppvGNWLYGKIENRFGFLLAQYV 739
Cdd:cd11820     3 VRALYDFEAAEDNELTFKAGEIITVLDDSD------PNWWKGSNHRGEGLFPANFV 52

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

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gi 392927372  683 FVRALEDYVTSEVNHLSFKQGDVIELLQEPEgetppvGNWLYGKIENRFGFLLAQYV 739
Cdd:cd11772     1 VFRALYDYEAQHPDELSFEEGDLLYISDKSD------PNWWKATCGGKTGLIPSNYV 51

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

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gi 392927372  684 VRALEDYVTSEVNHLSFKQGDVIELLQEPEgetppvGNWLYGKIENRFGFLLAQYVD 740
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDKIINIEFVD------DDWWLGECHGSRGLFPSNYVE 52

Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function. The related myosin XVa is important for normal growth of mechanosensory stereocilia of inner ear hair cells. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

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gi 392927372  683 FVRALEDYVTSEVNHLSFKQGDVIELLQEpEGETPpvgNWLYGKIENRFGFLLAQYV 739
Cdd:cd12068     1 YVVALRSYITDDKSLLSFHRGDLIKLLPM-AGLEP---GWQFGSTGGRSGLFPADIV 53

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

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gi 392927372  684 VRALEDYVTSEVNHLSFKQGDVIELLQepegETPPVGNWLYGKIENRFGFLLAQYV 739
Cdd:cd11841     2 VTALYSFEGQQPCDLSFQAGDRITVLT----RTDSQFDWWEGRLRGRVGIFPANYV 53