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 21313234   6 EEVNRLTENTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVSTELGHVLIEISSTHKKL 85
Cdd:cd07645   1 DEVNKLTESTYKNVMEQFNPGLRNLINLGKNYEKAVNAMVLAGKAYYDGVAKIGEIAAVSPVSKELGHVLMEISDVHKKL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234  86 NETLDENFKKFHKDIIHELEKKTELDVKYMNATLKRYQAEHRNKLDSLEKSQAELKKIRRKSQGGRNALKYEHKEIEYVE 165
Cdd:cd07645  81 NDSLEENFKKFHREIIAELERKTDLDVKYMTATLKRYQTEHKNKLDSLEKSQADLKKIRRKSQGRRNASKYEHKENEYLE 160

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21313234 166 TVTSRQSEIQKFIADGCKEALLEEKRRFCFLVDKHCSFASHIHYYHMQSAELLNSKLPRWQETCCD 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 21313234 498 VKLRPTVTNDRSAPII 513
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 21313234   6 EEVNRLTENTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVSTELGHVLIEISSTHKKL 85
Cdd:cd07645   1 DEVNKLTESTYKNVMEQFNPGLRNLINLGKNYEKAVNAMVLAGKAYYDGVAKIGEIAAVSPVSKELGHVLMEISDVHKKL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234  86 NETLDENFKKFHKDIIHELEKKTELDVKYMNATLKRYQAEHRNKLDSLEKSQAELKKIRRKSQGGRNALKYEHKEIEYVE 165
Cdd:cd07645  81 NDSLEENFKKFHREIIAELERKTDLDVKYMTATLKRYQTEHKNKLDSLEKSQADLKKIRRKSQGRRNASKYEHKENEYLE 160

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21313234 166 TVTSRQSEIQKFIADGCKEALLEEKRRFCFLVDKHCSFASHIHYYHMQSAELLNSKLPRWQETCCD 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 21313234 343 QKVKTIFPHTAGNNKTLLSFAQGDVLTLLIPEEKDGWLYGEHDTTKARGWFPSSYTKL 400
Cdd:cd11913   1 QKVKTIFPHTAGNNKTLLSFAQGDVITLLIPEEKDGWLYGEHDTTKARGWFPSSYTRP 58

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 21313234   348 IFPHTAGNnKTLLSFAQGDVLTlLIPEEKDGWLYGEhdTTKARGWFPSSYTK 399
Cdd:pfam14604   2 LYPYEPKD-DDELSLQRGDVIT-VIEESEDGWWEGI--NTGRTGLVPANYVE 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 21313234 498 VKLRPTVTNDRSAPII 513
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 21313234   6 EEVNRLTENTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVSTELGHVLIEISSTHKKL 85
Cdd:cd07645   1 DEVNKLTESTYKNVMEQFNPGLRNLINLGKNYEKAVNAMVLAGKAYYDGVAKIGEIAAVSPVSKELGHVLMEISDVHKKL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234  86 NETLDENFKKFHKDIIHELEKKTELDVKYMNATLKRYQAEHRNKLDSLEKSQAELKKIRRKSQGGRNALKYEHKEIEYVE 165
Cdd:cd07645  81 NDSLEENFKKFHREIIAELERKTDLDVKYMTATLKRYQTEHKNKLDSLEKSQADLKKIRRKSQGRRNASKYEHKENEYLE 160

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21313234 166 TVTSRQSEIQKFIADGCKEALLEEKRRFCFLVDKHCSFASHIHYYHMQSAELLNSKLPRWQETCCD 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 21313234   6 EEVNRLTENTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVSTELGHVLIEISSTHKKL 85
Cdd:cd07646   3 EEVNRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALASVTFAAKGYFDALVKMGELASESQGSKELGDVLFQMAEVHRQI 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234  86 NETLDENFKKFHKDIIHELEKKTELDVKYMNATLKRYQAEHRNKLDSLEKSQAELKKIRRKSQGGRNALKYEHKEIEYVE 165
Cdd:cd07646  83 QNQLEEMLKSFHNELLTQLEQKVELDSRYLTAALKKYQTEHRSKGESLEKCQAELKKLRKKSQGSKNPQKYSDKELQYIE 162

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234 166 TVTSRQSEIQKFIADGCKEALLEEKRRFCFLVDKHCSFASHIHYYHMQSAELLNSKLPRWQETCCDATKV 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 21313234  10 RLTENTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVSTELGHVLIEISSTHKKLNETL 89
Cdd:cd07644   5 RSTISIYKSIMEQFNPALENLVYLGNNYLRAFHALSEAAEVYFSAIAKIGEQALQSLTSQSLGEILIQMSETQRKLSADL 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234  90 DENFKKFHKDIIHELEKKTELDVKYMNATLKRYQAEHRNKLDSLEKSQAELKKIRRKSQggRNALkyehkeiEYVETVTS 169
Cdd:cd07644  85 EVVFQTFHVDLLQHMDKNTKLDMQFIEDSRRVYELEYRHRAANLEKCMSELWRMERQRD--RNVR-------EMKENVNR 155

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 21313234 170 RQSEIQKFIADGCKEALLEEKRRFCFLVDKHCSFASHIHYYHMQSAELLNSKLPRWQE 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 21313234 343 QKVKTIFPHTAGNnKTLLSFAQGDVLTLLIPEEKDGWLYGEHDTTKARGWFPSSYTK 399
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 21313234 344 KVKTIFPHTAGNNKTLLSFAQGDVLTLLIPEEKDGWLYGEHDTTKARGWFPSSYTKLL 401
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 21313234 344 KVKTIFPHTAgNNKTLLSFAQGDVLTlLIPEEKDGWLYGEHDTTKaRGWFPSSY 397
Cdd:cd00174   1 YARALYDYEA-QDDDELSFKKGDIIT-VLEKDDDGWWEGELNGGR-EGLFPANY 51

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234  26 GLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATgSPVSTELGHVLIEISSTHKKLNETLDENFKKFHKDIIHELE 105
Cdd:cd07307   8 LLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKELP-DLSNTDLGEALEKFGKIQKELEEFRDQLEQKLENKVIEPLK 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234 106 KKTELDVKYMNATLKRYQaEHRNKLDSLEKSQAELKKIRRKSQGGRNAL--------KYEHKEIEYVETVTSRQSEIQKF 177
Cdd:cd07307  87 EYLKKDLKEIKKRRKKLD-KARLDYDAAREKLKKLRKKKKDSSKLAEAEeelqeakeKYEELREELIEDLNKLEEKRKEL 165

                .
gi 21313234 178 I 178
Cdd:cd07307 166 F 166

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 21313234 344 KVKTIFPHTAGNNKTLlSFAQGDVLtLLIP-----EEKDGWLYGEHDTTKARGWFPSSYTKLL 401
Cdd:cd11790   4 KVRATHDYTAEDTDEL-TFEKGDVI-LVIPfddpeEQDEGWLMGVKESTGCRGVFPENFTERI 64

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. 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.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 21313234 360 LSFAQGDVLTLLiPEEKDGWLYGEHDTTKARGWFPSSYT 398
Cdd:cd11793  16 LTLEEGDVVNVL-RKMPDGWYEGERLRDGERGWFPSSYT 53

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), of Missing In Metastasis; 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. Members of this subfamily include missing in metastasis (MIM) or metastasis suppressor 1 (MTSS1), metastasis suppressor 1-like (MTSSL) or ABBA (Actin-Bundling protein with BAIAP2 homology), and similar proteins. They contain an N-terminal IMD and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. MIM was originally identified as a missing transcript from metastatic bladder and prostate cancer cells. It is a scaffold protein that functions in a signaling pathway between the PDGF receptor, Src kinases, and actin assembly. It may also function as a cofactor of the Sonic hedgehog (Shh) transcriptional pathway and may participate in tumor development and progression via this pathway. ABBA regulates actin and plasma membrane dynamics to promote the extension of radial glia, which is important in neuronal migration, axon guidance and neurogenesis. The IMD domain of MIM binds and bundles actin filaments, binds membranes, and interacts with the small GTPase Rac.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234  18 NVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGEIATGSPVST-ELGHVLIEISSTHKKLNETLDENFKKF 96
Cdd:cd07643  15 NDMKGSYPLWEDFVSKATKLHSQLRATIVATSAFLDAFQKIADAATNTRGATkEIGSALTRMCMRHKSIETKLKQFTSAL 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234  97 HKDIIHELEKKTELDVKYMNATLKRYQAEHRNKLDSLEKSQAELKKIRRKSQGGRNALKYEHKEieYVETVTSRQSEIQK 176
Cdd:cd07643  95 MDCLVNPLQEKIEEWKKVANQLDKDHAKEYKKARQEIKKKSSDTIRLQKKARKGKGDLQPQLDS--AMQDVNDKYLLLEE 172

                       170       180
                ....*....|....*....|.
gi 21313234 177 FIADGCKEALLEEKRRFCFLV 197
Cdd:cd07643 173 TEKKAVRNALIEERGRFCTFV 193

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ARHGEF16, also called ephexin-4, acts as a GEF for RhoG, activating it by exchanging bound GDP for free GTP. RhoG is a small GTPase that is a crucial regulator of Rac in migrating cells. ARHGEF16 interacts directly with the ephrin receptor EphA2 and mediates cell migration and invasion in breast cancer cells by activating RhoG. ARHGEF26, also called SGEF (SH3 domain-containing guanine exchange factor), also activates RhoG. It is highly expressed in liver and may play a role in regulating membrane dynamics. ARHGEF16 and ARHGEF26 contain 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 21313234 360 LSFAQGDVLtLLIPEEKDGWLYGEHDTTKARGWFPSSYTK 399
Cdd:cd11938  16 LSLQQADVV-LVLQTESDGWYYGERLRDGERGWFPSSCAK 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 21313234 344 KVKTIFPHTAGNNKTLlSFAQGDVLTLLIPEEKDgWLYGEHDTTKarGWFPSSYTKL 400
Cdd:cd11840   1 QVIALFPYTAQNEDEL-SFQKGDIINVLSKDDPD-WWRGELNGQT--GLFPSNYVEP 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 21313234 344 KVKTIFPHTAGNNKTLlSFAQGDVLTLLIPEEkDGWLYGEHDTTKarGWFPSSYTKL 400
Cdd:cd11877   1 LVRAKFNFEGTNEDEL-SFDKGDIITVTQVVE-GGWWEGTLNGKT--GWFPSNYVKE 53

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 21313234 360 LSFAQGDVLTLLipEEKDGWLYGEhdTTKARGWFPSSYTKL 400
Cdd:cd11990  16 LNFSKNDIITVL--EQQENWWFGE--VHGGRGWFPKSYVKL 52

Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. 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 21313234 354 GNNKTLLSFAQGDVLTLLIPEEKDGWLYGEHDTTKaRGWFPSSYTK 399
Cdd:cd11851  17 DDPEEELSFHAGDVVRVYGPMDEDGFYYGELEGGR-KGLVPSNFVQ 61

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 21313234 344 KVKTIFPHTAgNNKTLLSFAQGDVLTLLIPEEKDGWLYGEHDTTKaRGWFPSSY 397
Cdd:cd11763   1 KVRALYDFDS-QPSGELSLRAGEVLTITRQDVGDGWLEGRNSRGE-VGLFPSSY 52

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 21313234 360 LSFAQGDVLTLLIPEEKDgWLYGEHDTTKarGWFPSSYTKL 400
Cdd:cd11828  16 LGFKAGDVIEVLDMSDKD-WWWGSIRDEE--GWFPASFVRL 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21313234 356 NKTLLSFAQGDVLTLLIPEEkDGWLYGEHDTTKarGWFPSSYTK 399
Cdd:cd12061  12 NEDELSFSKGDVIHVTRVEE-GGWWEGTHNGRT--GWFPSNYVR 52

Src Homology 3 domain of CSK homologous kinase; CHK is also referred to as megakaryocyte-associated tyrosine kinase (Matk). It inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. To inhibit Src kinases that are anchored to the plasma membrane, CHK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CHK also plays a role in neural differentiation in a manner independent of Src by enhancing MAPK activation via Ras-mediated signaling. It is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase 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
                ....*....|....*....|....*....|..
gi 21313234 360 LSFAQGDVLTLLIPEEKDGWLYGEHDTTKARG 391
Cdd:cd11811  18 LAFHKGDIVTIVETCERKGWYRARHNTSGEEG 49

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. 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 21313234 346 KTIFPHTAGNNKTLlSFAQGDVLTLLIPEEKDgWLYGEHDTTKarGWFPSSYTKL 400
Cdd:cd11975   8 EAVWDHVTMANREL-AFKAGDVIKVLDASNKD-WWWGQIDDEE--GWFPASFVRL 58

Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function. The related myosin XVa is important for normal growth of mechanosensory stereocilia of inner ear hair cells. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. 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 21313234 355 NNKTLLSFAQGDVLTLLiPEE--KDGWLYGehdTTKAR-GWFPSSYTKL 400
Cdd:cd12068  11 DDKSLLSFHRGDLIKLL-PMAglEPGWQFG---STGGRsGLFPADIVQP 55

Src Homology 3 domain of Ras GTPase-Activating Protein 1; RasGAP, also called Ras p21 protein activator, RASA1, or p120RasGAP, is part of the GAP1 family of GTPase-activating proteins. It is a 120kD cytosolic protein containing an SH3 domain flanked by two SH2 domains at the N-terminal end, a pleckstrin homology (PH) domain, a calcium dependent phospholipid binding domain (CaLB/C2), and a C-terminal catalytic GAP domain. It stimulates the GTPase activity of normal RAS p21. It acts as a positive effector of Ras in tumor cells. It also functions as a regulator downstream of tyrosine receptors such as those of PDGF, EGF, ephrin, and insulin, among others. The SH3 domain of RasGAP is unable to bind proline-rich sequences but have been shown to interact with protein partners such as the G3BP protein, Aurora kinases, and the Calpain small subunit 1. The RasGAP SH3 domain is necessary for the downstream signaling of Ras and it also influences Rho-mediated cytoskeletal reorganization. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 21313234 342 KQKVKTIFPHTAGNNKTLLSFAQGDVLTLLiPEEKDGWLYGEHDTTKARG 391
Cdd:cd11788   1 RRRVRAILPYNKVPDTDELSFQKGDIFVVH-NELEDGWLWVTSLRTGESG 49

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234   70 ELGHVLIEISSTHKKLNET------LDENFKKF--HKDIIHELEKKTEL---DVKYMNATLK---RYQAEHRNKLDSLEK 135
Cdd:PRK03918 201 ELEEVLREINEISSELPELreelekLEKEVKELeeLKEEIEELEKELESlegSKRKLEEKIReleERIEELKKEIEELEE 280

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313234  136 SQAELKKIRRKSQGGR--NALKYEHKEIEY-----VETVTSRQSEIQKFIADG-CKEALLEE-KRRFCFLVDKHCSFASH 206
Cdd:PRK03918 281 KVKELKELKEKAEEYIklSEFYEEYLDELReiekrLSRLEEEINGIEERIKELeEKEERLEElKKKLKELEKRLEELEER 360

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 21313234  207 IHYYHMQSAELLNSKLPRWQETCcdatKVPEKIMNMIEEIKT 248
Cdd:PRK03918 361 HELYEEAKAKKEELERLKKRLTG----LTPEKLEKELEELEK 398

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 21313234 350 PHTAGNNKTLLSFAQGDVLTLLIPEEKDGWLYGEHDTTKARGWFPSSYTK 399
Cdd:cd11831  12 PPPPGAGGPVLTLQTGDVVELLKGDAESPWWEGRNVATREVGYFPSSSVK 61