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 1494845611  29 DPVYIDAERRFQELEAETKNLHDESKKYFEAINGMLNHQIEFSKAMTEIYKPISGRMSDPDSLIAQEnlDGIRACEEYEA 108
Cdd:cd07599     1 DEQFEELEKDFKSLEKSLKKLIEQSKAFRDSWRSILTHQIAFAKEFAELYDPIVGPKESVGSHPAPE--STLARLSRYVK 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611 109 VVRDLQETLAPELEMIDTRVVRPAQELMDVIKAIRKTATKREHKKLDYDRHRTTLKK-LQEKKERSAKDEKAMWKAENDV 187
Cdd:cd07599    79 ALEELKKELLEELEFFEERVILPAKELKKYIKKIRKTIKKRDHKKLDYDKLQNKLNKlLQKKKELSLKDEKQLAKLERKL 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1494845611 188 EQSTQEFNYFNDLLKDELPKLFALERDFIQPLFQSFYYMQLNIFYTLHERMQRVDIGY 245
Cdd:cd07599   159 EEAKEEYEALNELLKSELPKLLALADEFLPPLFKSFYYIQLNIYYTLHEYLQEFGEPQ 216

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 1494845611 408 TVTALYDYSAQAEGDLSFRAGDVIEIVSRTNNENEWWTGKIHGKQGQFPGYF 459
Cdd:cd11841     1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSQFDWWEGRLRGRVGIFPANY 52

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 1494845611  29 DPVYIDAERRFQELEAETKNLHDESKKYFEAINGMLNHQIEFSKAMTEIYKPISGRMSDPDSLIAQEnlDGIRACEEYEA 108
Cdd:cd07599     1 DEQFEELEKDFKSLEKSLKKLIEQSKAFRDSWRSILTHQIAFAKEFAELYDPIVGPKESVGSHPAPE--STLARLSRYVK 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611 109 VVRDLQETLAPELEMIDTRVVRPAQELMDVIKAIRKTATKREHKKLDYDRHRTTLKK-LQEKKERSAKDEKAMWKAENDV 187
Cdd:cd07599    79 ALEELKKELLEELEFFEERVILPAKELKKYIKKIRKTIKKRDHKKLDYDKLQNKLNKlLQKKKELSLKDEKQLAKLERKL 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1494845611 188 EQSTQEFNYFNDLLKDELPKLFALERDFIQPLFQSFYYMQLNIFYTLHERMQRVDIGY 245
Cdd:cd07599   159 EEAKEEYEALNELLKSELPKLLALADEFLPPLFKSFYYIQLNIYYTLHEYLQEFGEPQ 216

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611    5 GFQKGLIRAPQQFKAKFNVGENTK-DPVYIDAERRFQELEAETKNLHDESKKYFE---AINGMLNHQIEFSKAMTEIYKP 80
Cdd:smart00721   1 GFKKQFNRAKQKVGEKVGKAEKTKlDEDFEELERRFDTTEAEIEKLQKDTKLYLQpnpAVRAKLASQKKLSKSLGEVYEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611   81 IS-GRMSDPDSLIAQENLDGIRACEEYEAVVRDLQETLapelemiDTRVVRPAQELMDVIKAIRKTATKREHKKLDYDRH 159
Cdd:smart00721  81 GDdGEGLGADSSYGKALDKLGEALKKLLQVEESLSQVK-------RTFILPLLNFLLGEFKEIKKARKKLERKLLDYDSA 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611  160 RTTLKKLQEKKERSAKDEKAmwKAENDVEQSTQEFNYFNDLLKDELPKLFALERDFIQPLFQSFYYMQLNIFYTLHERMQ 239
Cdd:smart00721 154 RHKLKKAKKSKEKKKDEKLA--KAEEELRKAKQEFEESNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQ 231

                   ..
gi 1494845611  240 RV 241
Cdd:smart00721 232 QL 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 1494845611  618 KVETVTALYDYSAQAEGDLSFRAGDVIEIVSRtnNENEWWTGKIH-GKQGQFPGNYVQ 674
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEK--SDDGWWKGRLGrGKEGLFPSNYVE 56

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1494845611  405 KVETVTALYDYSAQAEGDLSFRAGDVIEIVSRtnNENEWWTGKIH-GKQGQFPGYF 459
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEK--SDDGWWKGRLGrGKEGLFPSNY 54

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 1494845611 410 TALYDYSAQAEGDLSFRAGDVIEIVSRtnNENEWWTGK-IHGKQGQFP 456
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEK--SEDGWWKGRnKGGKEGLIP 46

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 1494845611  29 DPVYIDAERRFQELEAETKNLHDESKKYFEAINGMLNHQIEFSKAMTEIYKPISGRMSDPDSLIAQEnlDGIRACEEYEA 108
Cdd:cd07599     1 DEQFEELEKDFKSLEKSLKKLIEQSKAFRDSWRSILTHQIAFAKEFAELYDPIVGPKESVGSHPAPE--STLARLSRYVK 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611 109 VVRDLQETLAPELEMIDTRVVRPAQELMDVIKAIRKTATKREHKKLDYDRHRTTLKK-LQEKKERSAKDEKAMWKAENDV 187
Cdd:cd07599    79 ALEELKKELLEELEFFEERVILPAKELKKYIKKIRKTIKKRDHKKLDYDKLQNKLNKlLQKKKELSLKDEKQLAKLERKL 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1494845611 188 EQSTQEFNYFNDLLKDELPKLFALERDFIQPLFQSFYYMQLNIFYTLHERMQRVDIGY 245
Cdd:cd07599   159 EEAKEEYEALNELLKSELPKLLALADEFLPPLFKSFYYIQLNIYYTLHEYLQEFGEPQ 216

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611    5 GFQKGLIRAPQQFKAKFNVGENTK-DPVYIDAERRFQELEAETKNLHDESKKYFE---AINGMLNHQIEFSKAMTEIYKP 80
Cdd:smart00721   1 GFKKQFNRAKQKVGEKVGKAEKTKlDEDFEELERRFDTTEAEIEKLQKDTKLYLQpnpAVRAKLASQKKLSKSLGEVYEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611   81 IS-GRMSDPDSLIAQENLDGIRACEEYEAVVRDLQETLapelemiDTRVVRPAQELMDVIKAIRKTATKREHKKLDYDRH 159
Cdd:smart00721  81 GDdGEGLGADSSYGKALDKLGEALKKLLQVEESLSQVK-------RTFILPLLNFLLGEFKEIKKARKKLERKLLDYDSA 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611  160 RTTLKKLQEKKERSAKDEKAmwKAENDVEQSTQEFNYFNDLLKDELPKLFALERDFIQPLFQSFYYMQLNIFYTLHERMQ 239
Cdd:smart00721 154 RHKLKKAKKSKEKKKDEKLA--KAEEELRKAKQEFEESNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQ 231

                   ..
gi 1494845611  240 RV 241
Cdd:smart00721 232 QL 233

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611  38 RFQELEAETKNLHDESKKYFEAINGMLNHQIEFSKAMTEIYKPisgrmsdpdsLIAQENLDGIRACEEYEAVVRDLQETL 117
Cdd:cd07307     1 KLDELEKLLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKE----------LPDLSNTDLGEALEKFGKIQKELEEFR 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611 118 APELEMIDTRVVRPAQELMDV-IKAIRKTATKREHKKLDYDRHRTTLKKLQEKKERSAKDEKAmwkaENDVEQSTQEFNY 196
Cdd:cd07307    71 DQLEQKLENKVIEPLKEYLKKdLKEIKKRRKKLDKARLDYDAAREKLKKLRKKKKDSSKLAEA----EEELQEAKEKYEE 146

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1494845611 197 FNDLLKDELPKLFALERDFIQPLFQSFYYMQLNIFYTLHERMQRVD 242
Cdd:cd07307   147 LREELIEDLNKLEEKRKELFLSLLLSFIEAQSEFFKEVLKILEQLL 192

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 1494845611 621 TVTALYDYSAQAEGDLSFRAGDVIEIVSRTNNENEWWTGKIHGKQGQFPGNYVQL 675
Cdd:cd11842     1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANYVEL 55

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1494845611 408 TVTALYDYSAQAEGDLSFRAGDVIEIVSRTNNENEWWTGKIHGKQGQFPGYF 459
Cdd:cd11841     1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSQFDWWEGRLRGRVGIFPANY 52

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 1494845611 408 TVTALYDYSAQAEGDLSFRAGDVIEIVSRTNNENEWWTGKIHGKQGQFPGYF 459
Cdd:cd11842     1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANY 52

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1494845611 622 VTALYDYSAQAEGDLSFRAGDVIEIVSRtnNENEWWTGKIHGKQGQFPGNYVQ 674
Cdd:cd11826     2 VVALYDYTADKDDELSFQEGDIIYVTKK--NDDGWYEGVLNGVTGLFPGNYVE 52

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1494845611  405 KVETVTALYDYSAQAEGDLSFRAGDVIEIVSRtnNENEWWTGKIH-GKQGQFPGYF 459
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEK--SDDGWWKGRLGrGKEGLFPSNY 54

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 1494845611 622 VTALYDYSAQAEGDLSFRAGDVIEIVSRTNneNEWWTGKIHGKQGQFPGNYVQ 674
Cdd:cd11805     2 VQALYDFNPQEPGELEFRRGDIITVLDSSD--PDWWKGELRGRVGIFPANYVQ 52

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 1494845611  27 TKDPVYIDAERRFQELEAETKNLHDESKKYFEAINGMLNHQIEFSKAMTEIYKPISGRMsdpdsliaqenldgIRACEEY 106
Cdd:cd07589     2 TKDKEFDELEKKFGSLEKQVQLVVRNVELYLQHVQESVLVKVLALEVVLDLYPSNHPRL--------------ESKWERF 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611 107 EAVVRDLQETLAPELEM-IDTRVVRPAQELMDVIKAIRKTATKREHKKLDYDRHrttlkklqekKERSAKDEKAMWKaen 185
Cdd:cd07589    68 RRVVRGISSKALPEFKSrVRKLVIEPLSSLLKLFSGPQKLIQKRYDKLLDYERY----------KEKKERGGKVDEE--- 134

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1494845611 186 dVEQSTQEFNYFNDLLKDELPKLFALERDFIQPLFQSFYYMQLNIFYTLHERMQRVDIGYFD 247
Cdd:cd07589   135 -LEEAANQYEALNAQLKEELPKFNQLTAQLLETCLKSFVELQRDLYDTLLKRAELLPLLDSS 195

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1494845611 622 VTALYDYSAQAEGDLSFRAGDVIEIVSRtnNENEWWTGKIHGKQGQFPGNYVQL 675
Cdd:cd11840     2 VIALFPYTAQNEDELSFQKGDIINVLSK--DDPDWWRGELNGQTGLFPSNYVEP 53

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 1494845611  20 KFNVGENTKDPVYIDAERRFQELEAETKNLHDESKKYFEAINGMLNHQIEFSKAMTEIYKPisgRMSDPDSLIAQ-ENLD 98
Cdd:cd07588     2 KLGKADETRDEVFDEHVNNFNKQQASANRLQKDLKNYLNSVRAMKQASKTLSETLKELYEP---DWPGREHLASIfEQLD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611  99 GIRAceeyeavvrDLQETLApelemidTRVVRPAQELMDVIKAIRKTATKREHKKLDYDRHRTTLKKLQEKKErsaKDEK 178
Cdd:cd07588    79 LLWN---------DLEEKLS-------DQVLGPLTAYQSQFPEVKKRIAKRGRKLVDYDSARHNLEALKAKKK---VDDQ 139

                         170       180       190
                  ....*....|....*....|....*....|.
gi 1494845611 179 AMWKAENDVEQSTQEFNYFNDLLKDELPKLF 209
Cdd:cd07588   140 KLTKAEEELQQAKKVYEELNTELHEELPALY 170

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 1494845611 411 ALYDYSAQAEGDLSFRAGDVIEIVSRtnNENEWWTGKIHGKQGQFPG 457
Cdd:cd11827     4 ALYAYDAQDTDELSFNEGDIIEILKE--DPSGWWTGRLRGKEGLFPG 48

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 1494845611 623 TALYDYSAQAEGDLSFRAGDVIEIVSRtnNENEWWTGK-IHGKQGQFP 669
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEK--SEDGWWKGRnKGGKEGLIP 46

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles 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 1494845611 624 ALYDYSAQAEGDLSFRAGDVIeIVSRTNNENeWWTGKIHGKQGQFPGNYVQ 674
Cdd:cd11786     4 ALYNYEGKEPGDLSFKKGDII-LLRKRIDEN-WYHGECNGKQGFFPASYVQ 52

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 1494845611 622 VTALYDYSAQAEGDLSFRAGDVIEIVSRTNneNEWWTGKIHGKQGQFPGNYV 673
Cdd:cd11950     2 VRALYDFEALEDDELGFNSGDVIEVLDSSN--PSWWKGRLHGKLGLFPANYV 51

The Bin/Amphiphysin/Rvs (BAR) domain of Amphiphysin I and II; 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. 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. The N-BAR domain of amphiphysin forms a curved dimer with a positively-charged concave face that can drive membrane bending and curvature. Human autoantibodies to amphiphysin-1 hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Mutations in amphiphysin-2 (BIN1) are associated with autosomal recessive centronuclear myopathy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611  20 KFNVGENTKDPVYIDAERRFQELEAETKNLHDESKKYFEAINGMLNHQIEFSKAMTEIYKP-ISGRmsdPDSLIAQENLD 98
Cdd:cd07611     2 KLGKADETKDEQFEEYVQNFKRQETEGTRLQRELRAYLAAIKGMQEASKKLTESLHEVYEPdWYGR---DDVKTIGEKCD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1494845611  99 GIraCEEYEavvrdlQETLAPELEMIDTRVVRpaqelmdvIKAIRKTATKREHKKLDYDRHRTTLKKLQEKKErsaKDEK 178
Cdd:cd07611    79 LL--WEDFH------QKLVDGALLTLDTYLGQ--------FPDIKNRIAKRSRKLVDYDSARHHLEALQTSKR---KDEG 139

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1494845611 179 AMWKAENDVEQSTQEFNYFNDLLKDELPKLFALERDFIQPLFQS 222
Cdd:cd07611   140 RIAKAEEEFQKAQKVFEEFNVDLQEELPSLWSRRVGFYVNTFKN 183

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 1494845611 621 TVTALYDYSAQAEGDLSFRAGDVIEIVSRTnnENEWWTGKIHGKQGQFPGNYVQL 675
Cdd:cd11877     1 LVRAKFNFEGTNEDELSFDKGDIITVTQVV--EGGWWEGTLNGKTGWFPSNYVKE 53

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 1494845611 621 TVTALYDYSAQAEGDLSFRAGDVIEIVSRTnnENEWWTGKIHGKQGQFPGNYVQL 675
Cdd:cd11961     1 WAKALYDYDAAEDNELSFFENDKIINIEFV--DDDWWLGECHGSRGLFPSNYVEL 53

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1494845611 622 VTALYDYSAQAEGDLSFRAGDVIEIVSRTNNENEWWTGKIHGKQGQFPGNYVQL 675
Cdd:cd11952     3 VYALWDYSAEFPDELSFKEGDMVTVLRKDGEGTDWWWASLCGREGYVPRNYFGL 56

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1494845611 625 LYDYSAQAEGDLSFRAGDVIEIVSRTNNENEWWTGKIHGKQGQFPGNYVQL 675
Cdd:cd12142     5 LFDYNPVAPDELALKKGDVIEVISKETEDEGWWEGELNGRRGFFPDNFVMP 55

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 1494845611 622 VTALYDYSAQAEGDLSFRAGDVIEIVSRTnnENEWWTGKIHGKQGQFPGNYVQ 674
Cdd:cd11951     2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCP--DPNWWRGRISGRVGFFPRNYVH 52

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 1494845611 410 TALYDYSAQAEGDLSFRAGDVIEIVSR---TNNENEWWTGKIHGKQGQFPGYF 459
Cdd:cd11876     3 TALFDYDARGEDELTLRRGQPVEVLSKdaaVSGDEGWWTGKIGDKVGIFPSNY 55

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles 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 1494845611 409 VTALYDYSAQAEGDLSFRAGDVIEIVSRTnnENEWWTGKIHGKQGQFPGYF 459
Cdd:cd11817     2 AVALYDFTGETEEDLSFQRGDRILVTEHL--DAEWSRGRLNGREGIFPRAF 50

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        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1494845611 621 TVTALYDYSAQAEGDLSFRAGDVIEIVSRTnnENEWWTGKIHGKQGQFPGNYV 673
Cdd:cd11873     1 EVIVEFDYDAEEPDELTLKVGDIITNVKKM--EEGWWEGTLNGKRGMFPDNFV 51

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1494845611 622 VTALYDYSAQAEGDLSFRAGDVIEIVsRTNNENEWWTGK-IHGKQGQFPGNYVQ 674
Cdd:cd11763     2 VRALYDFDSQPSGELSLRAGEVLTIT-RQDVGDGWLEGRnSRGEVGLFPSSYVE 54

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1494845611 409 VTALYDYSAQAEGDLSFRAGDVIEIVSRTNN--ENEWWTGKIHGKQGQFPGyfdltLDVEE 467
Cdd:cd11762     2 VRALYDYEAQSDEELSFPEGAIIRILRKDDNgvDDGWWEGEFNGRVGVFPS-----LVVEE 57

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 1494845611 621 TVTALYDYSAQAEGDLSFRAGDVIeivsrTNNE---NEWWTGKIHGKQGQFPGNYVQL 675
Cdd:cd11959     1 TAVALYDYQAADDDEISFDPDDII-----TNIEmidEGWWRGVCRGKYGLFPANYVEL 53