The Bin/Amphiphysin/Rvs (BAR) domain of Saccharomyces cerevisiae Reduced viability upon starvation protein 167 and similar proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of fungal proteins with similarity to Saccharomyces cerevisiae Reduced viability upon starvation protein 167 (Rvs167p) and Schizosaccharomyces pombe Hob1 (homolog of Bin1). S. cerevisiae Rvs167p plays a role in regulation of the actin cytoskeleton, endocytosis, and sporulation. It forms a heterodimer with another BAR domain protein Rvs161p. Rvs161p and Rvs167p share common functions but are not interchangeable. Their BAR domains cannot be replaced with each other and the overexpression of one cannot suppress the mutant phenotypes of the other. Rvs167p also interacts with the GTPase activating protein (GAP) Gyp5p, which is involved in ER to Golgi vesicle trafficking. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385  29 DAVYIDAERRFQELEKETKKLHDESKKYFEAINGMLQHQIDFSKAMTEIYKPISGRVSDPDSIKPegNPEGIRACEEYEA 108
Cdd:cd07599    1 DEQFEELEKDFKSLEKSLKKLIEQSKAFRDSWRSILTHQIAFAKEFAELYDPIVGPKESVGSHPA--PESTLARLSRYVK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385 109 VVQELQETLAPELETIETRVIRPANELLDVIKVIRKTAVKRDHKQLDYDRHRTTLKK-LQDKKDRSAKDEKAMWKAEGDC 187
Cdd:cd07599   79 ALEELKKELLEELEFFEERVILPAKELKKYIKKIRKTIKKRDHKKLDYDKLQNKLNKlLQKKKELSLKDEKQLAKLERKL 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 340520385 188 EQATQDFEYYNNLLKEELPKLFQLEQEFIKPLFQSFYYMQLNIFYTLHERMQRCDIGY 245
Cdd:cd07599  159 EEAKEEYEALNELLKSELPKLLALADEFLPPLFKSFYYIQLNIYYTLHEYLQEFGEPQ 216

The Bin/Amphiphysin/Rvs (BAR) domain of Saccharomyces cerevisiae Reduced viability upon starvation protein 167 and similar proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of fungal proteins with similarity to Saccharomyces cerevisiae Reduced viability upon starvation protein 167 (Rvs167p) and Schizosaccharomyces pombe Hob1 (homolog of Bin1). S. cerevisiae Rvs167p plays a role in regulation of the actin cytoskeleton, endocytosis, and sporulation. It forms a heterodimer with another BAR domain protein Rvs161p. Rvs161p and Rvs167p share common functions but are not interchangeable. Their BAR domains cannot be replaced with each other and the overexpression of one cannot suppress the mutant phenotypes of the other. Rvs167p also interacts with the GTPase activating protein (GAP) Gyp5p, which is involved in ER to Golgi vesicle trafficking. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385  29 DAVYIDAERRFQELEKETKKLHDESKKYFEAINGMLQHQIDFSKAMTEIYKPISGRVSDPDSIKPegNPEGIRACEEYEA 108
Cdd:cd07599    1 DEQFEELEKDFKSLEKSLKKLIEQSKAFRDSWRSILTHQIAFAKEFAELYDPIVGPKESVGSHPA--PESTLARLSRYVK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385 109 VVQELQETLAPELETIETRVIRPANELLDVIKVIRKTAVKRDHKQLDYDRHRTTLKK-LQDKKDRSAKDEKAMWKAEGDC 187
Cdd:cd07599   79 ALEELKKELLEELEFFEERVILPAKELKKYIKKIRKTIKKRDHKKLDYDKLQNKLNKlLQKKKELSLKDEKQLAKLERKL 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 340520385 188 EQATQDFEYYNNLLKEELPKLFQLEQEFIKPLFQSFYYMQLNIFYTLHERMQRCDIGY 245
Cdd:cd07599  159 EEAKEEYEALNELLKSELPKLLALADEFLPPLFKSFYYIQLNIYYTLHEYLQEFGEPQ 216

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385     5 GFQKSLVRAPQQFKSKFNIGEHTK-DAVYIDAERRFQELEKETKKLHDESKKYFE---AINGMLQHQIDFSKAMTEIYKP 80
Cdd:smart00721   1 GFKKQFNRAKQKVGEKVGKAEKTKlDEDFEELERRFDTTEAEIEKLQKDTKLYLQpnpAVRAKLASQKKLSKSLGEVYEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385    81 IsgrvsdpdsikpeGNPEGIRACEEYEAVVQELQETLAPELETIE-------TRVIRPANELLDVIKVIRKTAVKRDHKQ 153
Cdd:smart00721  81 G-------------DDGEGLGADSSYGKALDKLGEALKKLLQVEEslsqvkrTFILPLLNFLLGEFKEIKKARKKLERKL 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385   154 LDYDRHRTTLKKLQDKKDRSAKDEKAmwKAEGDCEQATQDFEYYNNLLKEELPKLFQLEQEFIKPLFQSFYYMQLNIFYT 233
Cdd:smart00721 148 LDYDSARHKLKKAKKSKEKKKDEKLA--KAEEELRKAKQEFEESNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRE 225

                   ....*...
gi 340520385   234 LHERMQRC 241
Cdd:smart00721 226 SYKLLQQL 233

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
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 340520385   373 PPETVTALYDYAAQAEGDLSFRAGDVIEIIQRtqNENEWWTGKVN-GKTGQFPGNYVK 429
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEK--SDDGWWKGRLGrGKEGLFPSNYVE 56

The Bin/Amphiphysin/Rvs (BAR) domain of Saccharomyces cerevisiae Reduced viability upon starvation protein 167 and similar proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of fungal proteins with similarity to Saccharomyces cerevisiae Reduced viability upon starvation protein 167 (Rvs167p) and Schizosaccharomyces pombe Hob1 (homolog of Bin1). S. cerevisiae Rvs167p plays a role in regulation of the actin cytoskeleton, endocytosis, and sporulation. It forms a heterodimer with another BAR domain protein Rvs161p. Rvs161p and Rvs167p share common functions but are not interchangeable. Their BAR domains cannot be replaced with each other and the overexpression of one cannot suppress the mutant phenotypes of the other. Rvs167p also interacts with the GTPase activating protein (GAP) Gyp5p, which is involved in ER to Golgi vesicle trafficking. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385  29 DAVYIDAERRFQELEKETKKLHDESKKYFEAINGMLQHQIDFSKAMTEIYKPISGRVSDPDSIKPegNPEGIRACEEYEA 108
Cdd:cd07599    1 DEQFEELEKDFKSLEKSLKKLIEQSKAFRDSWRSILTHQIAFAKEFAELYDPIVGPKESVGSHPA--PESTLARLSRYVK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385 109 VVQELQETLAPELETIETRVIRPANELLDVIKVIRKTAVKRDHKQLDYDRHRTTLKK-LQDKKDRSAKDEKAMWKAEGDC 187
Cdd:cd07599   79 ALEELKKELLEELEFFEERVILPAKELKKYIKKIRKTIKKRDHKKLDYDKLQNKLNKlLQKKKELSLKDEKQLAKLERKL 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 340520385 188 EQATQDFEYYNNLLKEELPKLFQLEQEFIKPLFQSFYYMQLNIFYTLHERMQRCDIGY 245
Cdd:cd07599  159 EEAKEEYEALNELLKSELPKLLALADEFLPPLFKSFYYIQLNIYYTLHEYLQEFGEPQ 216

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385     5 GFQKSLVRAPQQFKSKFNIGEHTK-DAVYIDAERRFQELEKETKKLHDESKKYFE---AINGMLQHQIDFSKAMTEIYKP 80
Cdd:smart00721   1 GFKKQFNRAKQKVGEKVGKAEKTKlDEDFEELERRFDTTEAEIEKLQKDTKLYLQpnpAVRAKLASQKKLSKSLGEVYEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385    81 IsgrvsdpdsikpeGNPEGIRACEEYEAVVQELQETLAPELETIE-------TRVIRPANELLDVIKVIRKTAVKRDHKQ 153
Cdd:smart00721  81 G-------------DDGEGLGADSSYGKALDKLGEALKKLLQVEEslsqvkrTFILPLLNFLLGEFKEIKKARKKLERKL 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385   154 LDYDRHRTTLKKLQDKKDRSAKDEKAmwKAEGDCEQATQDFEYYNNLLKEELPKLFQLEQEFIKPLFQSFYYMQLNIFYT 233
Cdd:smart00721 148 LDYDSARHKLKKAKKSKEKKKDEKLA--KAEEELRKAKQEFEESNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRE 225

                   ....*...
gi 340520385   234 LHERMQRC 241
Cdd:smart00721 226 SYKLLQQL 233

The Bin/Amphiphysin/Rvs (BAR) domain of Saccharomyces cerevisiae Reduced viability upon starvation protein 161 and similar proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of fungal proteins with similarity to Saccharomyces cerevisiae Reduced viability upon starvation protein 161 (Rvs161p) and Schizosaccharomyces pombe Hob3 (homolog of Bin3). S. cerevisiae Rvs161p plays a role in regulating cell polarity, actin cytoskeleton polarization, vesicle trafficking, endocytosis, bud formation, and the mating response. It forms a heterodimer with another BAR domain protein Rvs167p. Rvs161p and Rvs167p share common functions but are not interchangeable. Their BAR domains cannot be replaced with each other and the overexpression of one cannot suppress the mutant phenotypes of the other. S. pombe Hob3 is important in regulating filamentous actin localization and may be required in activating Cdc42 and recruiting it to cell division sites. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385  25 EHTKDAVYIDAERRFQELEKETKKLHDESKKYFEAINGMLQHQIDFSKAMTEIYKPisgrvsdpdsikpEGNPEGIRACE 104
Cdd:cd07591    6 ERTVDREFEFEERRYRTMEKASTKLQKEAKGYLDSLRALTSSQARIAETISSFYGD-------------AGDKDGAMLSQ 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385 105 EYEAVVQELQETLAPELET-IETRVIRPANELLDVIKVIRKTAVKRDHKQLDYDRHRTTLKKLQDKKDrsaKDEKAMWKA 183
Cdd:cd07591   73 EYKQAVEELDAETVKELDGpYRQTVLDPIGRFNSYFPEINEAIKKRNHKLLDYDAARAKVRKLIDKPS---EDPTKLPRA 149

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 340520385 184 EGDCEQATQDFEYYNNLLKEELPKLFQLEQEFIKPLFQSFYYMQLNIFYTLHERM---QRcdigYFD 247
Cdd:cd07591  150 EKELDEAKEVYETLNDQLKTELPQLVDLRIPYLDPSFEAFVKIQLRFFTEGYERLaqvQR----YLD 212

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 340520385 376 TVTALYDYAAQAEGDLSFRAGDVIEIIQRTQNENEWWTGKVNGKTGQFPGNYVKL 430
Cdd:cd11842    1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANYVEL 55

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 340520385 376 TVTALYDYAAQAEGDLSFRAGDVIEIIQRTqnENEWWTGKVN-GKTGQFPGNY 427
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKD--DDGWWEGELNgGREGLFPANY 51

The Bin/Amphiphysin/Rvs (BAR) domain of Dynamin Binding Protein; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. DyNamin Binding Protein (DNMBP), also called Tuba, is a Cdc42-specific Guanine nucleotide Exchange Factor (GEF) that binds dynamin and various actin regulatory proteins. It serves as a link between dynamin function, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. DNMBP contains BAR and SH3 domains as well as a Dbl Homology domain (DH domain), which harbors GEF activity. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of DNMBP may be involved in binding to membranes. The gene encoding DNMBP is a candidate gene for late onset Alzheimer's disease.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385  27 TKDAVYIDAERRFQELEKETKKLHDESKKYFEAINGMLQHQIDFSKAMTEIYkpisgrvsdpdsikPEGNPEGIRACEEY 106
Cdd:cd07589    2 TKDKEFDELEKKFGSLEKQVQLVVRNVELYLQHVQESVLVKVLALEVVLDLY--------------PSNHPRLESKWERF 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385 107 EAVVQELQETLAPELET-IETRVIRPANELLDVIKVIRKTAVKRDHKQLDYDRHRTtlkklqdkkdRSAKDEKAMWKAEg 185
Cdd:cd07589   68 RRVVRGISSKALPEFKSrVRKLVIEPLSSLLKLFSGPQKLIQKRYDKLLDYERYKE----------KKERGGKVDEELE- 136

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 340520385 186 dceQATQDFEYYNNLLKEELPKLFQLEQEFIKPLFQSFYYMQLNIFYTLHERMQRCDIGYFD 247
Cdd:cd07589  137 ---EAANQYEALNAQLKEELPKFNQLTAQLLETCLKSFVELQRDLYDTLLKRAELLPLLDSS 195

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 340520385 379 ALYDYAAQAEGDLSFRAGDVIEIiqrTQNENEWWTGKVNGKTGQFPGNYVKL 430
Cdd:cd11838    4 ALYPYESNEPGDLTFNAGDVILV---TKKDGEWWTGTIGDRTGIFPSNYVRP 52

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 340520385 376 TVTALYDYAAQAEGDLSFRAGDVIEIIQrtQNENEWWTGKVNGKTGQFPGNYVKL 430
Cdd:cd11877    1 LVRAKFNFEGTNEDELSFDKGDIITVTQ--VVEGGWWEGTLNGKTGWFPSNYVKE 53

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 340520385 379 ALYDYAAQAEGDLSFRAGDVIEIIQrtQNENEWWTGKVNGKTGQFPGNYV 428
Cdd:cd11827    4 ALYAYDAQDTDELSFNEGDIIEILK--EDPSGWWTGRLRGKEGLFPGNYV 51

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 340520385 379 ALYDYAAQAEGDLSFRAGDVIEIiqrTQNENEWWTGKVNGKTGQFPGNYVKL 430
Cdd:cd11991    4 AMYTYESNEQGDLTFQQGDVILV---TKKDGDWWTGTVGDKTGVFPSNYVRP 52

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 340520385 379 ALYDYAAQAEGDLSFRAGDVIEIiqrTQNENEWWTGKVNGKTGQFPGNYVK 429
Cdd:cd11992    4 ALYPYSSSEPGDLTFNEGEEILV---TQKDGEWWTGSIEDRTGIFPSNYVR 51

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 340520385  378 TALYDYAAQAEGDLSFRAGDVIEIIQRtqNENEWWTGKVN-GKTGQFP 424
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEK--SEDGWWKGRNKgGKEGLIP 46

The Bin/Amphiphysin/Rvs (BAR) domain of Amphiphysins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Amphiphysins function primarily in endocytosis and other membrane remodeling events. They contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. This subfamily is composed of different isoforms of amphiphysin and Bridging integrator 2 (Bin2). Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin and synaptojanin. They function in synaptic vesicle endocytosis. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Bin2 is mainly expressed in hematopoietic cells and is upregulated during granulocyte differentiation. The N-BAR domains of amphiphysins form a curved dimer with a positively-charged concave face that can drive membrane bending and curvature.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385  20 KFNIGEHTKDAVYIDAERRFQELEKETKKLHDESKKYFEAINGMLQHQIDFSKAMTEIYKP-ISGRvsdpdsikpegnpe 98
Cdd:cd07588    2 KLGKADETRDEVFDEHVNNFNKQQASANRLQKDLKNYLNSVRAMKQASKTLSETLKELYEPdWPGR-------------- 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 340520385  99 giraceEYEAVVQELQETLAPELE-TIETRVIRPANELLDVIKVIRKTAVKRDHKQLDYDRHRTTLKKLQDKKDrsaKDE 177
Cdd:cd07588   68 ------EHLASIFEQLDLLWNDLEeKLSDQVLGPLTAYQSQFPEVKKRIAKRGRKLVDYDSARHNLEALKAKKK---VDD 138

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 340520385 178 KAMWKAEGDCEQATQDFEYYNNLLKEELPKLFQLEQEFIKPLFQS 222
Cdd:cd07588  139 QKLTKAEEELQQAKKVYEELNTELHEELPALYDSRIAFYVDTLQS 183

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 340520385 378 TALYDYAAQAEGDLSFRAGDVIEIIQR---TQNENEWWTGKVNGKTGQFPGNYV 428
Cdd:cd11876    3 TALFDYDARGEDELTLRRGQPVEVLSKdaaVSGDEGWWTGKIGDKVGIFPSNYV 56

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        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 340520385 378 TALYDYAAQAEGDLSFRAGDVIEIIQrtQNENEWWTGKVNGKTGQFPGNYV 428
Cdd:cd11823    3 KALYSYTANREDELSLQPGDIIEVHE--KQDDGWWLGELNGKKGIFPATYV 51

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 340520385 379 ALYDYAAQAEGDLSFRAGDVIEIIQrtQNENEWWTGKVNGKTGQFPGNYV 428
Cdd:cd11772    4 ALYDYEAQHPDELSFEEGDLLYISD--KSDPNWWKATCGGKTGLIPSNYV 51

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 340520385 378 TALYDYAAQAEGDLSFRAGDVIEIIQR---TQNENEWWTGKVNGKTGQFPGNYV 428
Cdd:cd12058    3 TALYDYEASGEDELSLRRGDVVEVLSQdaaVSGDDGWWAGKIRHRLGIFPANYV 56

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 340520385 377 VTALYDYAAQAEGDLSFRAGDVIEIIQRTqnENEWWTGKVNGKTGQFPGNYVK 429
Cdd:cd11950    2 VRALYDFEALEDDELGFNSGDVIEVLDSS--NPSWWKGRLHGKLGLFPANYVA 52

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 340520385 377 VTALYDYAAQAEGDLSFRAGDVIEIIQRtqNENEWWTGKVNGKTGQFPGNYVKL 430
Cdd:cd11995    3 VIGMYDYTAQNDDELAFSKGQIINVLNK--EDPDWWKGELNGQVGLFPSNYVKL 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 340520385 377 VTALYDYAAQAEGDLSFRAGDVIEIIQRTqnENEWWTGKVNGKTGQFPGNYV 428
Cdd:cd11951    2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCP--DPNWWRGRISGRVGFFPRNYV 51

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 340520385 376 TVTALYDYAAQAEGDLSFRAGDVIEIIQrtQNENEWWTGKVNGKTGQFPGNYVKL 430
Cdd:cd11959    1 TAVALYDYQAADDDEISFDPDDIITNIE--MIDEGWWRGVCRGKYGLFPANYVEL 53

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 340520385 376 TVTALYDYAAQAEGDLSFRAGDVIEIIQRtQNENEWWTGKVNGKTGQFPGNYVK 429
Cdd:cd11830    1 TAKARYDFCARDMRELSLKEGDVVKIYNK-KGQQGWWRGEINGRIGWFPSTYVE 53

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 340520385 376 TVTALYDYAAQAEGDLSFRAGDVIEIIQRTqNENEWWTGKVNGKTGQFPGNYVKL 430
Cdd:cd11882    1 RARALYACKAEDESELSFEPGQIITNVQPS-DEPGWLEGTLNGRTGLIPENYVEF 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 340520385 376 TVTALYDYAAQAEGDLSFRAGDVIEIIQRtqnENEWWTGKV-NGKTGQFPGNYVKL 430
Cdd:cd11837    1 TATALYPWRAKKENHLSFAKGDIITVLEQ---QEMWWFGELeGGEEGWFPKSYVKE 53

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 340520385 380 LYDYAAQAEGDLSFRAGDVIEIIQRTQNENEWWTGKVNGKTGQFPGNYVKL 430
Cdd:cd12057    5 LFPYEAQNEDELTIKEGDIVTLISKDCIDAGWWEGELNGRRGVFPDNFVKL 55

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 340520385 377 VTALYDYAAQAEGDLSFRAGDVIEIIQRTQN--ENEWWTGKVNGKTGQFPG 425
Cdd:cd11762    2 VRALYDYEAQSDEELSFPEGAIIRILRKDDNgvDDGWWEGEFNGRVGVFPS 52

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 340520385 376 TVTALYDYAAQAEGDLSFRAGDVIEIIQRTqnENEWWTGKVNGKTGQFPGNYVKL 430
Cdd:cd11961    1 WAKALYDYDAAEDNELSFFENDKIINIEFV--DDDWWLGECHGSRGLFPSNYVEL 53

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 340520385 377 VTALYDYAAQAEGDLSFRAGDVIEIIQRTQN-ENEWWTGKVNGKTGQFPGNYVKL 430
Cdd:cd11954    3 VYALWDYEAQNADELSFQEGDAITILRRKDDsETEWWWARLNDKEGYVPKNLLGL 57

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 340520385 376 TVTALYDYAAQAEGDLSFRAGDVIEIIQRTQneNEWW--TGKVNGKTGQFPGNY 427
Cdd:cd11845    1 IYVALYDYEARTDDDLSFKKGDRLQILDDSD--GDWWlaRHLSTGKEGYIPSNY 52