Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; The IMD domain, also called Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions. This group is composed of uncharacterized proteins known as BAIAP2L2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2). They contain an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. The IMD domain binds and bundles actin filaments, binds membranes and produces membrane protrusions, and interacts with the small GTPase Rac.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971372596   2 DLSYRSTISIYKSILEQFNPALENLVYLGNNYLRAFHALSKAAEVYFKAVEKIGERALQSSTSHVLGEILMQMSDTQRLL 81
Cdd:cd07644    1 DLLYRSTISIYKSIMEQFNPALENLVYLGNNYLRAFHALSEAAEVYFSAIAKIGEQALQSLTSQSLGEILIQMSETQRKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971372596  82 SSDLEVVAQTFHVDLLQHMEKNSKMDVQFISESQKQYELEYRRKANNLEKCTTELWRMERARDKNVREMKENVMRLRSEM 161
Cdd:cd07644   81 SADLEVVFQTFHVDLLQHMDKNTKLDMQFIEDSRRVYELEYRHRAANLEKCMSELWRMERQRDRNVREMKENVNRLRQSM 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 971372596 162 QAFLSNSQREAELEEKRRYRFLAEKHQMLYNTLLQFYSRARGMIQTKAPQWKEQL 216
Cdd:cd07644  161 QAFLKESQRAAELEEKRRYRFLAEKHYLLNNTFLQFQSRARGMLQTRVPSWKEQP 215

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; The IMD domain, also called Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions. This group is composed of uncharacterized proteins known as BAIAP2L2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2). They contain an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. The IMD domain binds and bundles actin filaments, binds membranes and produces membrane protrusions, and interacts with the small GTPase Rac.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971372596   2 DLSYRSTISIYKSILEQFNPALENLVYLGNNYLRAFHALSKAAEVYFKAVEKIGERALQSSTSHVLGEILMQMSDTQRLL 81
Cdd:cd07644    1 DLLYRSTISIYKSIMEQFNPALENLVYLGNNYLRAFHALSEAAEVYFSAIAKIGEQALQSLTSQSLGEILIQMSETQRKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971372596  82 SSDLEVVAQTFHVDLLQHMEKNSKMDVQFISESQKQYELEYRRKANNLEKCTTELWRMERARDKNVREMKENVMRLRSEM 161
Cdd:cd07644   81 SADLEVVFQTFHVDLLQHMDKNTKLDMQFIEDSRRVYELEYRHRAANLEKCMSELWRMERQRDRNVREMKENVNRLRQSM 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 971372596 162 QAFLSNSQREAELEEKRRYRFLAEKHQMLYNTLLQFYSRARGMIQTKAPQWKEQL 216
Cdd:cd07644  161 QAFLKESQRAAELEEKRRYRFLAEKHYLLNNTFLQFQSRARGMLQTRVPSWKEQP 215

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 971372596 325 VRVQAIAPHTTGANRTLLRFDPGDVITVLMPEAQNGWLYGKLEGSSTCGWFPEAYVKPL 383
Cdd:cd11914    1 RRVRAIVSHPAGSNPTLLRFNRGDIITVLVPEARNGWLYGKLEGSSRQGWFPEAYVKAL 59

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 971372596   325 VRVQAIAPHTtGANRTLLRFDPGDVITVLmPEAQNGWLYGKLEGSSTcGWFPEAYVK 381
Cdd:smart00326   3 PQVRALYDYT-AQDPDELSFKKGDIITVL-EKSDDGWWKGRLGRGKE-GLFPSNYVE 56

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; The IMD domain, also called Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions. This group is composed of uncharacterized proteins known as BAIAP2L2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2). They contain an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. The IMD domain binds and bundles actin filaments, binds membranes and produces membrane protrusions, and interacts with the small GTPase Rac.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971372596   2 DLSYRSTISIYKSILEQFNPALENLVYLGNNYLRAFHALSKAAEVYFKAVEKIGERALQSSTSHVLGEILMQMSDTQRLL 81
Cdd:cd07644    1 DLLYRSTISIYKSIMEQFNPALENLVYLGNNYLRAFHALSEAAEVYFSAIAKIGEQALQSLTSQSLGEILIQMSETQRKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971372596  82 SSDLEVVAQTFHVDLLQHMEKNSKMDVQFISESQKQYELEYRRKANNLEKCTTELWRMERARDKNVREMKENVMRLRSEM 161
Cdd:cd07644   81 SADLEVVFQTFHVDLLQHMDKNTKLDMQFIEDSRRVYELEYRHRAANLEKCMSELWRMERQRDRNVREMKENVNRLRQSM 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 971372596 162 QAFLSNSQREAELEEKRRYRFLAEKHQMLYNTLLQFYSRARGMIQTKAPQWKEQL 216
Cdd:cd07644  161 QAFLKESQRAAELEEKRRYRFLAEKHYLLNNTFLQFQSRARGMLQTRVPSWKEQP 215

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), a dimerization module that binds and bends membranes; Inverse (I)-BAR (or IMD) is a member of the Bin/Amphiphysin/Rvs (BAR) domain family. It is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. IMD domains are found in Insulin Receptor tyrosine kinase Substrate p53 (IRSp53), Missing in Metastasis (MIM), and Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-like (BAIAP2L) proteins. These are multi-domain proteins that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. Most members contain an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus, exccept for MIM which does not carry an SH3 domain. Some members contain additional domains and motifs. The IMD domain binds and bundles actin filaments, binds membranes and produces membrane protrusions, and interacts with the small GTPase Rac.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971372596   5 YRSTISIYKSILEQFNPALENLVYLGNNYLRAFHALSKAAEVYFKAVEKIGERALQSSTSHVLGEILMQMSDTQRLLSSD 84
Cdd:cd07605    4 NRLTENIYKNIKEQFNPVLRNLIKAGKKYQKALQALSQAAKVFFDALAKIGELASQSRGSQELGEALKQIVDTHKSIEAS 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971372596  85 LEVVAQTFHVDLLQHMEKNSKMDVQFISESQKQYELEYRRKANNLEKCTTELWRMER--------ARDKNVREMKENVMR 156
Cdd:cd07605   84 LEQVAKAFHGELILPLEKKLELDQKVINKFEKDYKKEYKQKREDLDKARSELKKLQKksqksgtgKYQEKLDQALEELND 163

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 971372596 157 LRSEMQAFLSNSQREAELEEKRRYRFLAEKHQMLYNTLLQFYSRARGMIQTKAPQWKEQ 215
Cdd:cd07605  164 KQKELEAFVSQGLRDALLEERRRYCFLVDKHCSVAKHEIAYHAKAMTLLSTRLPLWQEL 222

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Insulin Receptor tyrosine kinase Substrate p53; The IMD domain, also called Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions. IRSp53 (Insulin Receptor tyrosine kinase Substrate p53) is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. Its IMD domain binds and bundles actin filaments, binds membranes, and interacts with the small GTPase Rac.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971372596   6 RSTISIYKSILEQFNPALENLVYLGNNYLRAFHALSKAAEVYFKAVEKIGERALQSSTSHVLGEILMQMSDTQRLLSSDL 85
Cdd:cd07646    7 RLTENVYKTIMEQFNPSLRNFIAMGKNYEKALASVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHRQIQNQL 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 971372596  86 EVVAQTFHVDLLQHMEKNSKMDVQFISESQKQYELEYRRKANNLEKCTTELWRMER----ARDKNVREMK-----ENVMR 156
Cdd:cd07646   87 EEMLKSFHNELLTQLEQKVELDSRYLTAALKKYQTEHRSKGESLEKCQAELKKLRKksqgSKNPQKYSDKelqyiEAISN 166

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 971372596 157 LRSEMQAFLSNSQREAELEEKRRYRFLAEKHQMLYNTLLQFYSRARGMIQTKAPQWKeqlEASRNPS 223
Cdd:cd07646  167 KQGELENYVSDGYKTALTEERRRYCFLVEKQCAVAKNSIAYHSKGKELLTQKLPSWQ---QACSDPN 230

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 971372596 326 RVQAIAPHTTGAnRTLLRFDPGDVITVLMPEAQNGWLYGKLEGSSTCGWFPEAYVKP 382
Cdd:cd11779    2 RVKALYPHAAGG-ETQLSFEEGDVITLLGPEPRDGWHYGENERSGRRGWFPIAYTEP 57

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53; IRSp53 is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 can also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRSp53 has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 971372596 326 RVQAIAPHTTGANRTLLRFDPGDVITVLMPEAQNGWLYGKLEGSSTCGWFPEAYVKPL 383
Cdd:cd11915    2 RVQAIFSHAAGDNSTLLSFKEGDYITLLVPEARDGWHYGECEKTKMRGWFPFSYTRVL 59

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 971372596 342 LRFDPGDVITVlmPEAQN---GWLYGKLEGSStcGWFPEAYV 380
Cdd:cd11836   16 ISFQPGDIIQV--DESQVaepGWLAGELKGKT--GWFPANYV 53

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 971372596 342 LRFDPGDVITVLmpEAQNGWLYGKLEGSSTcGWFPEAYVKP 382
Cdd:cd11837   16 LSFAKGDIITVL--EQQEMWWFGELEGGEE-GWFPKSYVKE 53

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 971372596   325 VRVQAIAPHTtGANRTLLRFDPGDVITVLmPEAQNGWLYGKLEGSSTcGWFPEAYVK 381
Cdd:smart00326   3 PQVRALYDYT-AQDPDELSFKKGDIITVL-EKSDDGWWKGRLGRGKE-GLFPSNYVE 56

First 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 first SH3 domain of Vav1 has been shown to bind the adaptor protein Grb2. 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 971372596 332 PHTTGANRTLLRFDPGDVITVLMPEAQNGWLYGKLEGSSTCGWFPEAYVKP 382
Cdd:cd11979   12 PPPPGAFGPFLRLNPGDIVELTKAEAEQNWWEGRNTSTNEIGWFPCNRVKP 62

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 971372596 335 TGANRTLLRFDPGDVITVLMPEAQNGWLYGKLEGSstCGWFPEAYVKP 382
Cdd:cd11882    9 KAEDESELSFEPGQIITNVQPSDEPGWLEGTLNGR--TGLIPENYVEF 54

Second Src homology 3 domain (or SH3B) 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 second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 971372596 342 LRFDPGDVITVLmpEAQNGWLYGKLEGSStcGWFPEAYVK 381
Cdd:cd11990   16 LNFSKNDIITVL--EQQENWWFGEVHGGR--GWFPKSYVK 51

Second Src homology 3 domain (or SH3B) 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 second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 971372596 342 LRFDPGDVITVLmpEAQNGWLYGKLEGSStcGWFPEAYVK 381
Cdd:cd11989   16 LNFNKNDVITVL--EQQDMWWFGEVQGQK--GWFPKSYVK 51

Fourth Src homology 3 domain (or SH3D) 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 fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. 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 971372596 328 QAIAPHT-TGANRtlLRFDPGDVITVLMPEAqNGWLYGKLEGSST---CGWFPEAYVK 381
Cdd:cd11839    3 QVIAPFTaTAENQ--LSLAVGQLVLVRKKSP-SGWWEGELQARGKkrqIGWFPANYVK 57

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
                  ....*....|....*....|....*....|....*....|....*....
gi 971372596  335 TGANRTLLRFDPGDVITVLmPEAQNGWLYGKLEGSStcGWFPEAYVKPL 383
Cdd:pfam07653   9 VGTDKNGLTLKKGDVVKVL-GKDNDGWWEGETGGRV--GLVPSTAVEEI 54

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.

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gi 971372596 326 RVQAIAPHTtGANRTLLRFDPGDVITVLMPEAQNgWLYGKLEGSStcGWFPEAYVKP 382
Cdd:cd11840    1 QVIALFPYT-AQNEDELSFQKGDIINVLSKDDPD-WWRGELNGQT--GLFPSNYVEP 53

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important 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.

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gi 971372596 338 NRTLLRFDPGDVITVLMPEaQNGWLYGKLEGSStcGWFPEAYVK 381
Cdd:cd12061   12 NEDELSFSKGDVIHVTRVE-EGGWWEGTHNGRT--GWFPSNYVR 52

First Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. 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 971372596 339 RTLLRFDPGDVITVLMPEAQNGWLYGKLEGSSTCGWFPEAYVKP 382
Cdd:cd11980   17 KPVLTFQTGDVIELLRGDPDSPWWEGRLLQTKKSGYFPSSSVKP 60

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. 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 971372596 347 GDVITVLMPEAQNGWLYGKLEGSstCGWFPEAYVK 381
Cdd:cd11978   22 GDVVKIYTKMSTNGWWRGEVNGR--VGWFPSTYVE 54

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

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gi 971372596 324 TVRVQAIAPHTtgaNRTLLRFDPGDVITVLMpEAQNGWLYGKLEGSSTC---GWFPEAY 379
Cdd:cd11883    1 VVVALYDFTPK---SKNQLSFKAGDIIYVLN-KDPSGWWDGVIISSSGKvkrGWFPSNY 55