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 767937745 275 TEDKEFDDLEERFQW-----------VSLCVTELKNNVAAYLDNLQAFLYFRPHEYNLDIPEgpAVQYCNLARDLHLEAF 343
Cdd:cd07589    2 TKDKEFDELEKKFGSlekqvqlvvrnVELYLQHVQESVLVKVLALEVVLDLYPSNHPRLESK--WERFRRVVRGISSKAL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745 344 LKFKQRLEGLVWQPLCSLAKALLGPQNLIKKRLDKLLDFERVEEKLLEVGSVTYQEEAARHTYQALNSLLVAELPQFNQL 423
Cdd:cd07589   80 PEFKSRVRKLVIEPLSSLLKLFSGPQKLIQKRYDKLLDYERYKEKKERGGKVDEELEEAANQYEALNAQLKEELPKFNQL 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 767937745 424 VMQWLGQIMCTFVTLQRDLAKQVLQRAEgsmaQLPHHHVP 463
Cdd:cd07589  160 TAQLLETCLKSFVELQRDLYDTLLKRAE----LLPLLDSS 195

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. 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 767937745 617 QVIAAYPFVARSSHEVSLQAGQPVTILEAQDKKGNPEWSLVEVNGQRGYVPSGFLAR 673
Cdd:cd11941    1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDKKGSPEWSLVEVNGQRGYVPSSYLAR 57

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 767937745 275 TEDKEFDDLEERFQW-----------VSLCVTELKNNVAAYLDNLQAFLYFRPHEYNLDIPEgpAVQYCNLARDLHLEAF 343
Cdd:cd07589    2 TKDKEFDELEKKFGSlekqvqlvvrnVELYLQHVQESVLVKVLALEVVLDLYPSNHPRLESK--WERFRRVVRGISSKAL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745 344 LKFKQRLEGLVWQPLCSLAKALLGPQNLIKKRLDKLLDFERVEEKLLEVGSVTYQEEAARHTYQALNSLLVAELPQFNQL 423
Cdd:cd07589   80 PEFKSRVRKLVIEPLSSLLKLFSGPQKLIQKRYDKLLDYERYKEKKERGGKVDEELEEAANQYEALNAQLKEELPKFNQL 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 767937745 424 VMQWLGQIMCTFVTLQRDLAKQVLQRAEgsmaQLPHHHVP 463
Cdd:cd07589  160 TAQLLETCLKSFVELQRDLYDTLLKRAE----LLPLLDSS 195

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745   45 AVRELIDTEVSYLHMLQLCASDIRSRLQQL---PQGDLDVLFSNIDDIIKVNSRFLhdlQETASKEEEQVQLVGNIFLEF 121
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPlseSEEEIKTIFSNIEEIYELHRQLL---LEELLKEWISIQRIGDIFLKF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745  122 QEELEqVYKVYCASYDQALllvDTYRKEPELQRHIQGIVEAVVPQAGSSGLSF--LLVIPLQRITRYPLLLQKILENTVP 199
Cdd:pfam00621  78 APGFK-VYSTYCSNYPKAL---KLLKKLLKKNPKFRAFLEELEANPECRGLDLnsFLIKPVQRIPRYPLLLKELLKHTPP 153

                         170       180
                  ....*....|....*....|...
gi 767937745  200 DASAYPVLQRAVSALQDVNTNIN 222
Cdd:pfam00621 154 DHPDYEDLKKALEAIKEVAKQIN 176

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. 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 767937745 617 QVIAAYPFVARSSHEVSLQAGQPVTILEAQDKKGNPEWSLVEVNGQRGYVPSGFLAR 673
Cdd:cd11941    1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDKKGSPEWSLVEVNGQRGYVPSSYLAR 57

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 767937745   617 QVIAAYPFVARSSHEVSLQAGQPVTILEaqdkKGNPEWSLVEVN-GQRGYVPSGFLA 672
Cdd:smart00326   4 QVRALYDYTAQDPDELSFKKGDIITVLE----KSDDGWWKGRLGrGKEGLFPSNYVE 56

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745   254 LSKKTTRLSQLLKQEAGLIPRTE-DKEFDDLEERFQ----WVSLCVTELKNnvaaYLDNLQA-----FLYFRPHE----- 318
Cdd:smart00721   2 FKKQFNRAKQKVGEKVGKAEKTKlDEDFEELERRFDtteaEIEKLQKDTKL----YLQPNPAvraklASQKKLSKslgev 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745   319 ---------YNLDIPEGPAVQYCNLARDLHLEAFLKFKQRLEGLVWQPLCSLAKALLGPQNLIKKRLDKLLDF------- 382
Cdd:smart00721  78 yeggddgegLGADSSYGKALDKLGEALKKLLQVEESLSQVKRTFILPLLNFLLGEFKEIKKARKKLERKLLDYdsarhkl 157

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767937745   383 ---ERVEEKLLEVGSVTYQEE--AARHTYQALNSLLVAELPQFNQLVMQWLGQIMCTFVTLQRDLAKQVLQRAE 451
Cdd:smart00721 158 kkaKKSKEKKKDEKLAKAEEElrKAKQEFEESNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQ 231

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 767937745  522 YQVTSNISGTGTLDLTLPRGQIVAILqnkDTKGNSGrWLVDTGGHRGYVPAGKLQLY 578
Cdd:pfam07653   2 GRVIFDYVGTDKNGLTLKKGDVVKVL---GKDNDGW-WEGETGGRVGLVPSTAVEEI 54

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 767937745 275 TEDKEFDDLEERFQW-----------VSLCVTELKNNVAAYLDNLQAFLYFRPHEYNLDIPEgpAVQYCNLARDLHLEAF 343
Cdd:cd07589    2 TKDKEFDELEKKFGSlekqvqlvvrnVELYLQHVQESVLVKVLALEVVLDLYPSNHPRLESK--WERFRRVVRGISSKAL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745 344 LKFKQRLEGLVWQPLCSLAKALLGPQNLIKKRLDKLLDFERVEEKLLEVGSVTYQEEAARHTYQALNSLLVAELPQFNQL 423
Cdd:cd07589   80 PEFKSRVRKLVIEPLSSLLKLFSGPQKLIQKRYDKLLDYERYKEKKERGGKVDEELEEAANQYEALNAQLKEELPKFNQL 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 767937745 424 VMQWLGQIMCTFVTLQRDLAKQVLQRAEgsmaQLPHHHVP 463
Cdd:cd07589  160 TAQLLETCLKSFVELQRDLYDTLLKRAE----LLPLLDSS 195

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745   45 AVRELIDTEVSYLHMLQLCASDIRSRLQQL---PQGDLDVLFSNIDDIIKVNSRFLhdlQETASKEEEQVQLVGNIFLEF 121
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKPlseSEEEIKTIFSNIEEIYELHRQLL---LEELLKEWISIQRIGDIFLKF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745  122 QEELEqVYKVYCASYDQALllvDTYRKEPELQRHIQGIVEAVVPQAGSSGLSF--LLVIPLQRITRYPLLLQKILENTVP 199
Cdd:pfam00621  78 APGFK-VYSTYCSNYPKAL---KLLKKLLKKNPKFRAFLEELEANPECRGLDLnsFLIKPVQRIPRYPLLLKELLKHTPP 153

                         170       180
                  ....*....|....*....|...
gi 767937745  200 DASAYPVLQRAVSALQDVNTNIN 222
Cdd:pfam00621 154 DHPDYEDLKKALEAIKEVAKQIN 176

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. 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 767937745 617 QVIAAYPFVARSSHEVSLQAGQPVTILEAQDKKGNPEWSLVEVNGQRGYVPSGFLAR 673
Cdd:cd11941    1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDKKGSPEWSLVEVNGQRGYVPSSYLAR 57

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. 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 767937745 617 QVIAAYPFVARSSHEVSLQAGQPVTILEAQDKKGNPEWSLVEVNGQRGYVPSGFLAR 673
Cdd:cd11800    1 YYYALYTFEARSPGELSVTEGQVVTVLEKHDLKGNPEWWLVEDRGKQGYVPSNYLAK 57

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. 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 767937745 617 QVIAAYPFVARSSHEVSLQAGQPVTILEaqdkKGNPEWSLVEVNGQRGYVPSGFL 671
Cdd:cd11856    1 SYVAIADYEAQGDDEISLQEGEVVEVLE----KNDSGWWYVRKGDKEGWVPASYL 51

BAR domain; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different protein families. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysin, endophilin, BRAP and Nadrin. BAR domains are also frequently found alongside domains that determine lipid specificity, like pfam00169 and pfam00787 domains in beta centaurins and sorting nexins respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745  254 LSKKTTRLSQLLKQEAGLIPRTE-DKEFDDLEERFQWVSLCVTELKNNVAAYLDNLQAFlyfRPHEYNLDIPE------- 325
Cdd:pfam03114   1 LKKQFNRASQLLGEKVGGAEKTKlDEDFEELERRFDTTEKEIKKLQKDTKGYLQPNPGA---RAKQTVLEQPEellaesm 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767937745  326 -------------GPAVQYCNLARDLHLEAFLKFKQRLEGLVWQPLCSLAKALLGPQNLIKKRLDKLLDF---------- 382
Cdd:pfam03114  78 ieagkdlgedssfGKALEDYGEALKRLAQLLEQLDDRVETNFLDPLRNLLKEFKEIQKHRKKLERKRLDYdaaktrvkka 157

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767937745  383 ERVEEKLLEVGSVTYQE-EAARHTYQALNSLLVAELPQFNQLVMQWLGQIMCTFVTLQRDLAKQVLQRaegsMAQL 457
Cdd:pfam03114 158 KKKKSSKAKDESQAEEElRKAQAKFEESNEQLKALLPNLLSLEVEFVVNQLVAFVEAQLDFHRQCYQL----LEQL 229

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. 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 767937745 529 SGTGTLDLTLPRGQIVAILQNKDTKGNSGRWLVDTGGHRGYVPAGKLQ 576
Cdd:cd11800    9 EARSPGELSVTEGQVVTVLEKHDLKGNPEWWLVEDRGKQGYVPSNYLA 56

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 767937745 617 QVIAAYPFVARSSHEVSLQAGQPVTILEaqdkKGNPEWSLVEVN-GQRGYVPSGF 670
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLE----KDDDGWWEGELNgGREGLFPANY 51

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 767937745  620 AAYPFVARSSHEVSLQAGQPVTILEaqdkKGNPEWSLVEVNGQRGYVPSGFLA 672
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIE----ESEDGWWEGINTGRTGLVPANYVE 49

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. 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 767937745 618 VIAAYPFVARSSHEVSLQAGQPVTILEAQDKkgnpEWSLVEVNGQRGYVPSGFLAR 673
Cdd:cd11808    2 VVALYDYQEKSPREVSMKKGDILTLLNSSNK----DWWKVEVNDRQGFVPAAYVKK 53

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. 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 767937745 617 QVIAAYPFVARSSHEVSLQAGQPVTILeaqDKKGNPEWSLVE--VNGQRGYVPSGFL 671
Cdd:cd11775    2 RGKVLYDFDAQSDDELTVKEGDVVYIL---DDKKSKDWWMVEnvSTGKEGVVPASYI 55

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, 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 767937745 619 IAAYPFVARSSHEVSLQAGQPVTILEaqdkKGNPEWSLVEVNGQRGYVPSGFL 671
Cdd:cd11824    3 SVLYDYTAQEDDELSISKGDVVAVIE----KGEDGWWTVERNGQKGLVPGTYL 51

Fifth Src homology 3 domain (or SH3E) 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 fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which 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.

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gi 767937745 617 QVIAAYPFVARSSHEVSLQAGQPVTILEaqdkKGNPEWSLVEVNGQRGYVPSGFL 671
Cdd:cd11996    2 QVIAMYDYTANNEDELSFSKGQLINVLN----KDDPDWWQGEINGVTGLFPSNYV 52

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases 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). 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.

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gi 767937745 618 VIAAYPFVARSSHEVSLQAGQPVTILeaqdkKGNPEWSLVE--VNGQRGYVPSGFLAR 673
Cdd:cd12009    2 VIAQYDFVPSNERDLQLKKGEKLQVL-----KSDGEWWLAKslTTGKEGYIPSNYVAR 54

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.

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gi 767937745 617 QVIAAYPFVARSSHEVSLQAGQPVTILEAQDkkgnPEWSLVEVNGQRGYVPSGFL 671
Cdd:cd11995    2 QVIGMYDYTAQNDDELAFSKGQIINVLNKED----PDWWKGELNGQVGLFPSNYV 52

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 767937745 535 DLTLPRGQIVAILQNKDTKGNSGRWLVDTGGHRGYVPA 572
Cdd:cd12141   15 ELSVSANQRVRILEFSDLTGNKEWWLAEANGQKGYVPS 52

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.

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gi 767937745 619 IAAYPFVARSSHEVSLQAGQPVTILeaqDKKGNPEWSLVEVNGQRGYVPSGFL 671
Cdd:cd11830    3 KARYDFCARDMRELSLKEGDVVKIY---NKKGQQGWWRGEINGRIGWFPSTYV 52

First Src homology 3 domain (or SH3A) 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 first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, 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.

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gi 767937745 620 AAYPFVARSSHEVSLQAGQPVTILEAQDkkGNPEWSLVEVNGQRGYVPSGF 670
Cdd:cd11836    4 ALYAFEARNPDEISFQPGDIIQVDESQV--AEPGWLAGELKGKTGWFPANY 52

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];

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gi 767937745   83 FSNIDDIIKVNSRFLHDLQETASKEEeQVQLVGNIFLEFQEELEQVYKvYCASYDQALLLVDTYRK-EPELQRHIQGIVE 161
Cdd:COG5422   533 FANINEIYAVNSKLLKALTNRQCLSP-IVNGIADIFLDYVPKFEPFIK-YGASQPYAKYEFEREKSvNPNFARFDHEVER 610

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gi 767937745  162 AVVPQagSSGLSFLLVIPLQRITRYPLLLQKILENTVPDASAYPVLQRAVSALQDVNTNIN 222
Cdd:COG5422   611 LDESR--KLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLN 669

First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 767937745 624 FVARSSHEVSLQAGQPVTILEAQDKKgnPEWSLVEVNG------QRGYVPSGFLA 672
Cdd:cd11852    9 FEATSSQELTVSKGQTVEVLERPSSR--PDWCLVRTLEqdnsppQEGLVPSSILC 61

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. 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 C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 767937745 620 AAYPFVARSSHEVSLQAGQPVTILeaqDKKGNPEWSLVEVNGQRGYVPSGFL 671
Cdd:cd11976    4 ARYDFCARDRSELSLKEGDIIKIL---NKKGQQGWWRGEIYGRVGWFPANYV 52

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.

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gi 767937745 618 VIAAYPFVARSSHEVSLQAGQPVTILEAQDKKgNPEWSLVEVNGQRGYVPSGFL 671
Cdd:cd11954    3 VYALWDYEAQNADELSFQEGDAITILRRKDDS-ETEWWWARLNDKEGYVPKNLL 55

Second or C-terminal Src homology 3 domain of NADPH oxidase (Nox) Organizing protein 1; Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1 is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. NoxO1 contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of NoxO1. The tandem SH3 domains of NoxO1 interact with the PRR of p22phox, which also complexes with Nox1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 767937745 620 AAYPFVARSSHEVSLQAGQPVTILEAQDKKgnpeWSLVEVNGQRGYVPSGFL 671
Cdd:cd12024    4 ATRAYEAQKEDELSVPAGVVVEVLQKSDNG----WWLIRYNGRAGYVPSMYL 51

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 767937745 617 QVIAAYPFVARSSHEVSLQAGQPVTILEAQDKKGnpeWSLV-EVNGQRGYVPSGFL 671
Cdd:cd11911    1 TCTALYDFDGTSEGTLSMEEGEILLVLEEDGGDG---WTRVrKNNGDEGYVPTSYI 53

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 767937745 618 VIAAYPFVARSSHEVSLQAGQPVTILEAQDKKGnpeWSLVEVNGQRGYVPSGFL 671
Cdd:cd11905    3 VVAMYDFQPTEPHDLRLETGEEYVILEKNDVHW---WKARDKYGKEGYIPSNYV 53