Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1; 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. BAIAP2L1 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1) is also known as IRTKS (Insulin Receptor Tyrosine Kinase Substrate). It is widely expressed, 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. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. It contains an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The IMD domain of BAIAP2L1 binds and bundles actin filaments, and binds the small GTPase Rac.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32171238   6 EEVNRLTESTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVSTELGHVLIEISSTHKKL 85
Cdd:cd07645   1 DEVNKLTESTYKNVMEQFNPGLRNLINLGKNYEKAVNAMVLAGKAYYDGVAKIGEIAAVSPVSKELGHVLMEISDVHKKL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32171238  86 NESLDENFKKFHKEIIHELEKKIELDVKYMNATLKRYQTEHKNKLESLEKSQAELKKIRRKSQGSRNALKYEHKEIEYVE 165
Cdd:cd07645  81 NDSLEENFKKFHREIIAELERKTDLDVKYMTATLKRYQTEHKNKLDSLEKSQADLKKIRRKSQGRRNASKYEHKENEYLE 160

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 32171238 166 TVTSRQSEIQKFIADGCKEALLEEKRRFCFLVDKHCGFANHIHYYHLQSAELLNSKLPRWQETCVD 231
Cdd:cd07645 161 TVTSRQSDIQKFIADGCREALLEEKRRFCFLVDKHCSFSNHIHYFHQQAAELLNSKLPVWQETCSD 226

Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif), and similar proteins; This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) as well as thymosin-beta (Tbeta; also called beta-thymosin or betaT) domains that are small, widespread intrinsically disordered actin-binding peptides displaying significant sequence variability and different regulations of actin self-assembly in motile and morphogenetic processes. These WH2/betaT peptides are identified by a central consensus actin-binding motif LKKT/V flanked by variable N-terminal and C-terminal extensions; the betaT shares a more extended and conserved C-terminal half than WH2. These single or repeated domains are found in actin-binding proteins (ABPs) such as the hematopoietic-specific protein WASP, its ubiquitously expressed ortholog neural-WASP (N-WASP), WASP-interacting protein (WAS/WASL-interacting protein family members 1 and 2), and WASP-family verprolin homologous protein (WAVE/SCAR) isoforms: WAVE1, WAVE2, and WAVE3. Also included are the WH2 domains found in inverted formin FH2 domain-containing protein (INF2), Cordon bleu (Cobl) protein, vasodilator-stimulated phosphoprotein (VASP) homology protein and actobindin (found in amoebae). These ABPs are commonly multidomain proteins that contain signaling domains and structurally conserved actin-binding motifs, the most important being the WH2 domain motif through which they bind actin in order to direct the location, rate, and timing for actin assembly in the cell into different structures, such as filopodia, lamellipodia, stress fibers, and focal adhesions. The WH2 domain motif is one of the most abundant actin-binding motifs in Wiskott-Aldrich syndrome proteins (WASPs) where they activate Arp2/3-dependent actin nucleation and branching in response to signals mediated by Rho-family GTPases. The thymosin beta (Tbeta) domains in metazoans act in cells as major actin-sequestering peptides; their complex with monomeric ATP-actin (G-ATP-actin) cannot polymerize at either filament (F-actin) end.

                        10
                ....*....|....*.
gi 32171238 495 VKLRPTVTNDRSAPII 510
Cdd:cd22060  16 VKLRKTVTNDRSAPRI 31

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1; 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. BAIAP2L1 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1) is also known as IRTKS (Insulin Receptor Tyrosine Kinase Substrate). It is widely expressed, 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. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. It contains an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The IMD domain of BAIAP2L1 binds and bundles actin filaments, and binds the small GTPase Rac.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32171238   6 EEVNRLTESTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVSTELGHVLIEISSTHKKL 85
Cdd:cd07645   1 DEVNKLTESTYKNVMEQFNPGLRNLINLGKNYEKAVNAMVLAGKAYYDGVAKIGEIAAVSPVSKELGHVLMEISDVHKKL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32171238  86 NESLDENFKKFHKEIIHELEKKIELDVKYMNATLKRYQTEHKNKLESLEKSQAELKKIRRKSQGSRNALKYEHKEIEYVE 165
Cdd:cd07645  81 NDSLEENFKKFHREIIAELERKTDLDVKYMTATLKRYQTEHKNKLDSLEKSQADLKKIRRKSQGRRNASKYEHKENEYLE 160

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 32171238 166 TVTSRQSEIQKFIADGCKEALLEEKRRFCFLVDKHCGFANHIHYYHLQSAELLNSKLPRWQETCVD 231
Cdd:cd07645 161 TVTSRQSDIQKFIADGCREALLEEKRRFCFLVDKHCSFSNHIHYFHQQAAELLNSKLPVWQETCSD 226

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1, also called Insulin Receptor Tyrosine Kinase Substrate (IRTKS); BAIAP2L1 or IRTKS is widely expressed, 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. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. IRTKS mediates the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. 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 SH3 domain of IRTKS 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 32171238 342 QKVKTIFPHTAGSNKTLLSFAQGDVITLLIPEEKDGWLYGEHDVSKARGWFPSSYTKL 399
Cdd:cd11913   1 QKVKTIFPHTAGNNKTLLSFAQGDVITLLIPEEKDGWLYGEHDTTKARGWFPSSYTRP 58

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 32171238   347 IFPHTAGsNKTLLSFAQGDVITlLIPEEKDGWLYGEHDVSkaRGWFPSSYTK 398
Cdd:pfam14604   2 LYPYEPK-DDDELSLQRGDVIT-VIEESEDGWWEGINTGR--TGLVPANYVE 49

Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Metastasis suppressor protein 1 (MTSS-1); This family contains the first tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in metastasis suppressor protein 1 (MTSS1, also called also known as missing in metastasis or MIM). MTSS1 may be related to cancer progression or tumor metastasis in a variety of organ sites, most likely through an interaction with the actin cytoskeleton. It interacts with actin via its WH2 domain. MTSS1 is a novel potential metastasis suppressor gene in several types of human cancers; its expression is down-regulated in ovarian cancer, colorectal cancer, oesophageal cancer, prostate cancer and breast cancer, whereas it has also been observed to be up-regulated in hepato-cellular carcinoma and breast cancer.

                        10
                ....*....|....*.
gi 32171238 495 VKLRPTVTNDRSAPII 510
Cdd:cd22060  16 VKLRKTVTNDRSAPRI 31

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1; 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. BAIAP2L1 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1) is also known as IRTKS (Insulin Receptor Tyrosine Kinase Substrate). It is widely expressed, 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. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. It contains an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The IMD domain of BAIAP2L1 binds and bundles actin filaments, and binds the small GTPase Rac.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32171238   6 EEVNRLTESTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVSTELGHVLIEISSTHKKL 85
Cdd:cd07645   1 DEVNKLTESTYKNVMEQFNPGLRNLINLGKNYEKAVNAMVLAGKAYYDGVAKIGEIAAVSPVSKELGHVLMEISDVHKKL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32171238  86 NESLDENFKKFHKEIIHELEKKIELDVKYMNATLKRYQTEHKNKLESLEKSQAELKKIRRKSQGSRNALKYEHKEIEYVE 165
Cdd:cd07645  81 NDSLEENFKKFHREIIAELERKTDLDVKYMTATLKRYQTEHKNKLDSLEKSQADLKKIRRKSQGRRNASKYEHKENEYLE 160

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 32171238 166 TVTSRQSEIQKFIADGCKEALLEEKRRFCFLVDKHCGFANHIHYYHLQSAELLNSKLPRWQETCVD 231
Cdd:cd07645 161 TVTSRQSDIQKFIADGCREALLEEKRRFCFLVDKHCSFSNHIHYFHQQAAELLNSKLPVWQETCSD 226

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 32171238   6 EEVNRLTESTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVSTELGHVLIEISSTHKKL 85
Cdd:cd07646   3 EEVNRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALASVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHRQI 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32171238  86 NESLDENFKKFHKEIIHELEKKIELDVKYMNATLKRYQTEHKNKLESLEKSQAELKKIRRKSQGSRNALKYEHKEIEYVE 165
Cdd:cd07646  83 QNQLEEMLKSFHNELLTQLEQKVELDSRYLTAALKKYQTEHRSKGESLEKCQAELKKLRKKSQGSKNPQKYSDKELQYIE 162

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32171238 166 TVTSRQSEIQKFIADGCKEALLEEKRRFCFLVDKHCGFANHIHYYHLQSAELLNSKLPRWQETCVDAIKV 235
Cdd:cd07646 163 AISNKQGELENYVSDGYKTALTEERRRYCFLVEKQCAVAKNSIAYHSKGKELLTQKLPSWQQACSDPNKI 232

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 32171238  10 RLTESTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVSTELGHVLIEISSTHKKLNESL 89
Cdd:cd07644   5 RSTISIYKSIMEQFNPALENLVYLGNNYLRAFHALSEAAEVYFSAIAKIGEQALQSLTSQSLGEILIQMSETQRKLSADL 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32171238  90 DENFKKFHKEIIHELEKKIELDVKYMNATLKRYQTEHKNKLESLEKSQAELKKIRRksQGSRNALkyehkeiEYVETVTS 169
Cdd:cd07644  85 EVVFQTFHVDLLQHMDKNTKLDMQFIEDSRRVYELEYRHRAANLEKCMSELWRMER--QRDRNVR-------EMKENVNR 155

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 32171238 170 RQSEIQKFIADGCKEALLEEKRRFCFLVDKHCGFANHIHYYHLQSAELLNSKLPRWQE 227
Cdd:cd07644 156 LRQSMQAFLKESQRAAELEEKRRYRFLAEKHYLLNNTFLQFQSRARGMLQTRVPSWKE 213

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 32171238 342 QKVKTIFPHTAGSnKTLLSFAQGDVITLLIPEEKDGWLYGEHDVSKARGWFPSSYTK 398
Cdd:cd11779   1 PRVKALYPHAAGG-ETQLSFEEGDVITLLGPEPRDGWHYGENERSGRRGWFPIAYTE 56

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 32171238 343 KVKTIFPHTAGSNKTLLSFAQGDVITLLIPEEKDGWLYGEHDVSKARGWFPSSYTKLL 400
Cdd:cd11914   2 RVRAIVSHPAGSNPTLLRFNRGDIITVLVPEARNGWLYGKLEGSSRQGWFPEAYVKAL 59

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 32171238 343 KVKTIFPHTAgSNKTLLSFAQGDVITlLIPEEKDGWLYGEHDvSKARGWFPSSY 396
Cdd:cd00174   1 YARALYDYEA-QDDDELSFKKGDIIT-VLEKDDDGWWEGELN-GGREGLFPANY 51

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 32171238 343 KVKTIFPHTAGSNKTLlSFAQGDVITLLipEEKDGWLYGE-HDVSkaRGWFPSSYTKL 399
Cdd:cd11837   1 TATALYPWRAKKENHL-SFAKGDIITVL--EQQEMWWFGElEGGE--EGWFPKSYVKE 53

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 32171238   347 IFPHTAGsNKTLLSFAQGDVITlLIPEEKDGWLYGEHDVSkaRGWFPSSYTK 398
Cdd:pfam14604   2 LYPYEPK-DDDELSLQRGDVIT-VIEESEDGWWEGINTGR--TGLVPANYVE 49

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        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 32171238 343 KVKTIFPHTAGSNKTLlSFAQGDVITLLipEEKDGWLYGEhdVSKARGWFPSSYTKL 399
Cdd:cd11989   1 QAQALYPWRAKKDNHL-NFNKNDVITVL--EQQDMWWFGE--VQGQKGWFPKSYVKL 52

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. 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. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. 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. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins 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. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 32171238 343 KVKTIFPHTAgSNKTLLSFAQGDVItLLIP-----EEKDGWLYGEHDVSKARGWFPSSYTKLL 400
Cdd:cd11790   4 KVRATHDYTA-EDTDELTFEKGDVI-LVIPfddpeEQDEGWLMGVKESTGCRGVFPENFTERI 64

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 32171238 354 SNKTLLSFAQGDVITLLipeEKD--GW---LYGEHDVSKARGWFPSSY 396
Cdd:cd11883  11 KSKNQLSFKAGDIIYVL---NKDpsGWwdgVIISSSGKVKRGWFPSNY 55

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 32171238 343 KVKTIFPHTAgSNKTLLSFAQGDVITLLIPEEKDgWLYGEhdVSKARGWFPSSYTKL 399
Cdd:cd11840   1 QVIALFPYTA-QNEDELSFQKGDIINVLSKDDPD-WWRGE--LNGQTGLFPSNYVEP 53

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.

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gi 32171238 343 KVKTIFPHTaGSNKTLLSFAQGDVITLLIPEEkDGWLYGEHDVSKarGWFPSSYTKL 399
Cdd:cd11877   1 LVRAKFNFE-GTNEDELSFDKGDIITVTQVVE-GGWWEGTLNGKT--GWFPSNYVKE 53

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

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gi 32171238 343 KVKTIFPHTAgSNKTLLSFAQGDVITLLIPEEKDGWLYGEhdVSKARGWFPSSYTKL 399
Cdd:cd11882   1 RARALYACKA-EDESELSFEPGQIITNVQPSDEPGWLEGT--LNGRTGLIPENYVEF 54

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH 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.

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gi 32171238 343 KVKTIFPHTAgSNKTLLSFAQGDVITLLiPEEKDGWLYGEHDVSKARGWFPSSYTK 398
Cdd:cd11939   1 QVQCVHPYVS-QEPDELSLELADVLNIL-DKTDDGWIFGERLHDQERGWFPSSVVE 54

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 32171238 359 LSFAQGDVITLLIPEEKDgWLYGEhdVSKARGWFPSSYTKL 399
Cdd:cd11828  16 LGFKAGDVIEVLDMSDKD-WWWGS--IRDEEGWFPASFVRL 53

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 32171238 343 KVKTIFPHTAgSNKTLLSFAQGDVITllIPEEKD---GWLYGEhdVSKARGWFPSSY 396
Cdd:cd11836   1 KYRALYAFEA-RNPDEISFQPGDIIQ--VDESQVaepGWLAGE--LKGKTGWFPANY 52

First Src homology 3 domain (or SH3A) 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 first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind 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 32171238 345 KTIFPHTAgSNKTLLSFAQGDVITLlipEEKD----GWLYGEHdvSKARGWFPSSY 396
Cdd:cd11988   5 RALYPFEA-RNHDEMSFNAGDIIQV---DEKTvgepGWLYGSF--QGNFGWFPCNY 54

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. 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 32171238 359 LSFAQGDVITLLiPEEKDGWLYGEHDVSKarGWFPSSYT 397
Cdd:cd11766  16 LSLRKGDRVLVL-EKSSDGWWRGECNGQV--GWFPSNYV 51

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 32171238 344 VKTIFPHTAGSNKTLLSFAQGDVITLLIPEEKDGWLYGEHDVSKARGWFPSSYTK 398
Cdd:cd11980   5 VQNYHGNPAPPGKPVLTFQTGDVIELLRGDPDSPWWEGRLLQTKKSGYFPSSSVK 59

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 32171238 359 LSFAQGDVITLLIPEEKDGWLYGEhdVSKARGWFPSSYTK 398
Cdd:cd11978  17 LSLLKGDVVKIYTKMSTNGWWRGE--VNGRVGWFPSTYVE 54

Fourth Src homology 3 domain (or SH3D) 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 fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which 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.

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gi 32171238 343 KVKTIFPhTAGSNKtlLSFAQGDVItLLIPEEKDGWLYGEHDV---SKARGWFPSSYTKLL 400
Cdd:cd11994   3 QVTTAYV-ASGVEQ--LSLSPGQLI-LILKKNSSGWWLGELQArgkKRQKGWFPASHVKLL 59

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. 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 32171238 344 VKTIFPHTAgSNKTLLSFAQGDVITLLIPEEkDGWLYGEHDvSKARGWFPSSYTK 398
Cdd:cd11825   2 VKALYDYRA-QRPDELSFCKHAIITNVEKED-GGWWRGDYG-GKKQKWFPANYVE 53

Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Metastasis suppressor protein 1 (MTSS-1); This family contains the first tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in metastasis suppressor protein 1 (MTSS1, also called also known as missing in metastasis or MIM). MTSS1 may be related to cancer progression or tumor metastasis in a variety of organ sites, most likely through an interaction with the actin cytoskeleton. It interacts with actin via its WH2 domain. MTSS1 is a novel potential metastasis suppressor gene in several types of human cancers; its expression is down-regulated in ovarian cancer, colorectal cancer, oesophageal cancer, prostate cancer and breast cancer, whereas it has also been observed to be up-regulated in hepato-cellular carcinoma and breast cancer.

                        10
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gi 32171238 495 VKLRPTVTNDRSAPII 510
Cdd:cd22060  16 VKLRKTVTNDRSAPRI 31

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 32171238 343 KVKTIFPHTAgSNKTLLSFAQGDVITLLIPEEKDGWlygEHDVSKARGWFPSSYTKL 399
Cdd:cd11995   2 QVIGMYDYTA-QNDDELAFSKGQIINVLNKEDPDWW---KGELNGQVGLFPSNYVKL 54