ID VAV_HUMAN Reviewed; 845 AA. AC P15498; B4DVK9; M0QXX6; Q15860; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 21-FEB-2001, sequence version 4. DT 03-AUG-2022, entry version 240. DE RecName: Full=Proto-oncogene vav; GN Name=VAV1; Synonyms=VAV; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF CYS-529. RX PubMed=2069873; RA Coppola J., Bryant S., Koda T., Conway D., Barbacid M.; RT "Mechanism of activation of the vav protooncogene."; RL Cell Growth Differ. 2:95-105(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10760587; DOI=10.1016/s0167-4781(00)00008-7; RA Denkinger D.J., Borges C.R., Butler C.L., Cushman A.M., Kawahara R.S.; RT "Genomic organization and regulation of the vav proto-oncogene."; RL Biochim. Biophys. Acta 1491:253-262(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-61. RX PubMed=2005887; DOI=10.1128/mcb.11.4.1912-1920.1991; RA Katzav S., Cleveland J.L., Heslop H.E., Pulido D.; RT "Loss of the amino-terminal helix-loop-helix domain of the vav proto- RT oncogene activates its transforming potential."; RL Mol. Cell. Biol. 11:1912-1920(1991). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 51-813 (ISOFORM 2). RC TISSUE=Spleen; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 68-845 (ISOFORM 1). RX PubMed=2477241; DOI=10.1002/j.1460-2075.1989.tb08354.x; RA Katzav S., Martin-Zanca D., Barbacid M.; RT "vav, a novel human oncogene derived from a locus ubiquitously expressed in RT hematopoietic cells."; RL EMBO J. 8:2283-2290(1989). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 299-837 (ISOFORM 1). RA Romero F.; RL Submitted (JAN-1995) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 299-334 (ISOFORM 1). RX PubMed=7478592; RA Ramos-Morales F., Romero F., Schweighoffer F., Bismuth G., Camonis J., RA Tortolero M., Fischer S.; RT "The proline-rich region of Vav binds to Grb2 and Grb3-3."; RL Oncogene 11:1665-1669(1995). RN [9] RP SIMILARITY TO CDC24 FAMILY. RX PubMed=1565462; RA Adams J.M., Houston H., Allen J., Lints T., Harvey R.; RT "The hematopoietically expressed vav proto-oncogene shares homology with RT the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) RT involved in cytoskeletal organization."; RL Oncogene 7:611-618(1992). RN [10] RP INTERACTION WITH SYK, AND MUTAGENESIS OF ARG-696. RX PubMed=8986718; DOI=10.1016/s1074-7613(00)80273-3; RA Deckert M., Tartare-Deckert S., Couture C., Mustelin T., Altman A.; RT "Functional and physical interactions of Syk family kinases with the Vav RT proto-oncogene product."; RL Immunity 5:591-604(1996). RN [11] RP INTERACTION WITH CBLB. RX PubMed=9399639; DOI=10.1038/sj.onc.1201430; RA Bustelo X.R., Crespo P., Lopez-Barahona M., Gutkind J.S., Barbacid M.; RT "Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated RT c-Jun N-terminal kinase activation."; RL Oncogene 15:2511-2520(1997). RN [12] RP INTERACTION WITH BLNK; PLCG1; GRB2 AND NCK1. RX PubMed=9697839; DOI=10.1016/s1074-7613(00)80591-9; RA Fu C., Turck C.W., Kurosaki T., Chan A.C.; RT "BLNK: a central linker protein in B cell activation."; RL Immunity 9:93-103(1998). RN [13] RP INTERACTION WITH SIAH2. RX PubMed=10207103; DOI=10.1128/mcb.19.5.3798; RA Germani A., Romero F., Houlard M., Camonis J., Gisselbrecht S., Fischer S., RA Varin-Blank N.; RT "hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling RT pathways."; RL Mol. Cell. Biol. 19:3798-3807(1999). RN [14] RP PHOSPHORYLATION BY FYN. RX PubMed=11005864; DOI=10.1073/pnas.97.20.10923; RA Huang J., Tilly D., Altman A., Sugie K., Grey H.M.; RT "T-cell receptor antagonists induce Vav phosphorylation by selective RT activation of Fyn kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 97:10923-10929(2000). RN [15] RP INTERACTION WITH DOCK2. RX PubMed=12393632; DOI=10.1182/blood-2001-11-0032; RA Nishihara H., Maeda M., Oda A., Tsuda M., Sawa H., Nagashima K., Tanaka S.; RT "DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell RT lines."; RL Blood 100:3968-3974(2002). RN [16] RP INTERACTION WITH SHB. RX PubMed=12084069; DOI=10.1046/j.1432-1033.2002.03008.x; RA Lindholm C.K., Henriksson M.L., Hallberg B., Welsh M.; RT "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells."; RL Eur. J. Biochem. 269:3279-3288(2002). RN [17] RP INTERACTION WITH SH2B2. RX PubMed=12400014; DOI=10.1038/sj.onc.1205927; RA Yabana N., Shibuya M.; RT "Adaptor protein APS binds the NH2-terminal autoinhibitory domain of RT guanine nucleotide exchange factor Vav3 and augments its activity."; RL Oncogene 21:7720-7729(2002). RN [18] RP INTERACTION WITH ITK. RX PubMed=15661896; DOI=10.4049/jimmunol.174.3.1385; RA Dombroski D., Houghtling R.A., Labno C.M., Precht P., Takesono A., RA Caplen N.J., Billadeau D.D., Wange R.L., Burkhardt J.K., Schwartzberg P.L.; RT "Kinase-independent functions for Itk in TCR-induced regulation of Vav and RT the actin cytoskeleton."; RL J. Immunol. 174:1385-1392(2005). RN [19] RP INTERACTION WITH NEK3. RX PubMed=15618286; DOI=10.1210/me.2004-0443; RA Miller S.L., DeMaria J.E., Freier D.O., Riegel A.M., Clevenger C.V.; RT "Novel association of Vav2 and Nek3 modulates signaling through the human RT prolactin receptor."; RL Mol. Endocrinol. 19:939-949(2005). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-826, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [21] RP INTERACTION WITH ZNF655/VIK. RX PubMed=15558030; DOI=10.1038/sj.onc.1208043; RA Houlard M., Romero-Portillo F., Germani A., Depaux A., Regnier-Ricard F., RA Gisselbrecht S., Varin-Blank N.; RT "Characterization of VIK-1: a new Vav-interacting Kruppel-like protein."; RL Oncogene 24:28-38(2005). RN [22] RP INTERACTION WITH PTK2B/PYK2. RX PubMed=19207108; DOI=10.1042/bj20090037; RA Gao C., Blystone S.D.; RT "A Pyk2-Vav1 complex is recruited to beta3-adhesion sites to initiate Rho RT activation."; RL Biochem. J. 420:49-56(2009). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [24] RP INTERACTION WITH CRACR2A. RX PubMed=27016526; DOI=10.1126/scisignal.aac9171; RA Srikanth S., Kim K.D., Gao Y., Woo J.S., Ghosh S., Calmettes G., Paz A., RA Abramson J., Jiang M., Gwack Y.; RT "A large Rab GTPase encoded by CRACR2A is a component of subsynaptic RT vesicles that transmit T cell activation signals."; RL Sci. Signal. 9:ra31-ra31(2016). RN [25] RP STRUCTURE BY NMR OF 661-775. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the SH2 domain of human proto-oncogene protein RT VAV1."; RL Submitted (NOV-2005) to the PDB data bank. CC -!- FUNCTION: Couples tyrosine kinase signals with the activation of the CC Rho/Rac GTPases, thus leading to cell differentiation and/or CC proliferation. CC -!- SUBUNIT: Interacts with SHB (PubMed:12084069). Interacts with SH2B2, CC GRB2, GRB3, DOCK2, SLA, TEC and ZNF655/VIK (PubMed:12393632, CC PubMed:12400014, PubMed:15558030). Interacts with SIAH2; without CC leading to its degradation (PubMed:10207103). Associates with BLNK, CC PLCG1, GRB2 and NCK1 in a B-cell antigen receptor-dependent fashion CC (PubMed:9697839). Interacts with CBLB; which inhibits tyrosine CC phosphorylation and down-regulates activity (PubMed:9399639). May CC interact with CCPG1. Interacts with CLNK. Interacts with THEMIS2 (By CC similarity). Interacts with NEK3 and this interaction is prolactin- CC dependent (PubMed:15618286). Interacts with ITK (PubMed:15661896). CC Interacts with PTK2B/PYK2 (By similarity). Interacts with HCK. CC Interacts with PTK2B/PYK2 (PubMed:19207108). Interacts (via SH2 domain) CC with SYK (PubMed:8986718). Interacts with ANKRD54. Interacts with CD6 CC (By similarity). Interacts with isoform 2 of CRACR2A (PubMed:27016526). CC {ECO:0000250|UniProtKB:P27870, ECO:0000269|PubMed:10207103, CC ECO:0000269|PubMed:12084069, ECO:0000269|PubMed:12393632, CC ECO:0000269|PubMed:12400014, ECO:0000269|PubMed:15558030, CC ECO:0000269|PubMed:15618286, ECO:0000269|PubMed:15661896, CC ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:27016526, CC ECO:0000269|PubMed:8986718, ECO:0000269|PubMed:9399639, CC ECO:0000269|PubMed:9697839}. CC -!- INTERACTION: CC P15498; Q8IZP0: ABI1; NbExp=2; IntAct=EBI-625518, EBI-375446; CC P15498; P00519: ABL1; NbExp=5; IntAct=EBI-625518, EBI-375543; CC P15498; Q13480: GAB1; NbExp=2; IntAct=EBI-625518, EBI-517684; CC P15498; P62993: GRB2; NbExp=3; IntAct=EBI-625518, EBI-401755; CC P15498; Q07666: KHDRBS1; NbExp=3; IntAct=EBI-625518, EBI-1364; CC P15498; Q13094: LCP2; NbExp=9; IntAct=EBI-625518, EBI-346946; CC P15498; P63000: RAC1; NbExp=2; IntAct=EBI-625518, EBI-413628; CC P15498; P78314: SH3BP2; NbExp=8; IntAct=EBI-625518, EBI-727062; CC P15498; Q8N720: ZNF655; NbExp=5; IntAct=EBI-625518, EBI-625509; CC P15498; P08487: PLCG1; Xeno; NbExp=4; IntAct=EBI-625518, EBI-8013886; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P15498-1; Sequence=Displayed; CC Name=2; CC IsoId=P15498-2; Sequence=VSP_047563; CC -!- TISSUE SPECIFICITY: Widely expressed in hematopoietic cells but not in CC other cell types. CC -!- DOMAIN: The DH domain is involved in interaction with CCPG1. CC {ECO:0000250}. CC -!- PTM: Phosphorylated on tyrosine residues by HCK in response to IFNG and CC bacterial lipopolysaccharide (LPS) (By similarity). Phosphorylated by CC FYN. {ECO:0000250, ECO:0000269|PubMed:11005864}. CC -!- MISCELLANEOUS: 'Vav' stands for the sixth letter of the Hebrew CC alphabet. CC -!- SEQUENCE CAUTION: CC Sequence=BAG62721.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA34383.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/VAV1ID195ch19p13.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF030227; AAC25011.1; -; Genomic_DNA. DR EMBL; AF030201; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030202; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030203; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030204; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030205; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030206; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030207; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030208; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030209; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030210; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030211; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030212; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030213; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030214; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030215; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030216; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030217; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030218; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030219; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030220; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030221; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030222; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030223; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030224; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030225; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AF030226; AAC25011.1; JOINED; Genomic_DNA. DR EMBL; AC010647; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC020895; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC020954; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC022156; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M59834; AAA63267.1; -; Genomic_DNA. DR EMBL; AK301128; BAG62721.1; ALT_INIT; mRNA. DR EMBL; X16316; CAA34383.1; ALT_FRAME; mRNA. DR EMBL; X83931; CAA58783.1; -; mRNA. DR CCDS; CCDS12174.1; -. [P15498-1] DR CCDS; CCDS59342.1; -. [P15498-2] DR PIR; B39576; TVHUVV. DR RefSeq; NP_001245136.1; NM_001258207.1. [P15498-2] DR RefSeq; NP_005419.2; NM_005428.3. [P15498-1] DR PDB; 2CRH; NMR; -; A=629-775. DR PDB; 2LCT; NMR; -; A=664-767. DR PDB; 2MC1; NMR; -; A=664-767. DR PDB; 2ROR; NMR; -; A=629-775. DR PDB; 3BJI; X-ray; 2.60 A; A/B=189-565. DR PDB; 3KY9; X-ray; 2.73 A; A/B=2-584. DR PDB; 6NEW; X-ray; 2.50 A; A=170-575. DR PDB; 6NF1; X-ray; 2.60 A; A=2-575. DR PDB; 6NFA; X-ray; 2.70 A; A=170-575. DR PDBsum; 2CRH; -. DR PDBsum; 2LCT; -. DR PDBsum; 2MC1; -. DR PDBsum; 2ROR; -. DR PDBsum; 3BJI; -. DR PDBsum; 3KY9; -. DR PDBsum; 6NEW; -. DR PDBsum; 6NF1; -. DR PDBsum; 6NFA; -. DR AlphaFoldDB; P15498; -. DR BMRB; P15498; -. DR SMR; P15498; -. DR BioGRID; 113252; 188. DR CORUM; P15498; -. DR DIP; DIP-1061N; -. DR IntAct; P15498; 139. DR MINT; P15498; -. DR STRING; 9606.ENSP00000472929; -. DR BindingDB; P15498; -. DR ChEMBL; CHEMBL3259472; -. DR iPTMnet; P15498; -. DR PhosphoSitePlus; P15498; -. DR BioMuta; VAV1; -. DR DMDM; 13124807; -. DR CPTAC; CPTAC-1226; -. DR CPTAC; CPTAC-1227; -. DR EPD; P15498; -. DR jPOST; P15498; -. DR MassIVE; P15498; -. DR MaxQB; P15498; -. DR PaxDb; P15498; -. DR PeptideAtlas; P15498; -. DR PRIDE; P15498; -. DR ProteomicsDB; 53143; -. [P15498-1] DR Antibodypedia; 665; 764 antibodies from 42 providers. DR DNASU; 7409; -. DR Ensembl; ENST00000596764.5; ENSP00000469450.1; ENSG00000141968.8. [P15498-2] DR Ensembl; ENST00000602142.6; ENSP00000472929.1; ENSG00000141968.8. [P15498-1] DR GeneID; 7409; -. DR KEGG; hsa:7409; -. DR MANE-Select; ENST00000602142.6; ENSP00000472929.1; NM_005428.4; NP_005419.2. DR UCSC; uc002mfu.3; human. [P15498-1] DR CTD; 7409; -. DR DisGeNET; 7409; -. DR GeneCards; VAV1; -. DR HGNC; HGNC:12657; VAV1. DR HPA; ENSG00000141968; Tissue enhanced (bone marrow, lymphoid tissue). DR MIM; 164875; gene. DR neXtProt; NX_P15498; -. DR OpenTargets; ENSG00000141968; -. DR PharmGKB; PA37280; -. DR VEuPathDB; HostDB:ENSG00000141968; -. DR eggNOG; KOG2996; Eukaryota. DR GeneTree; ENSGT00940000159125; -. DR InParanoid; P15498; -. DR OMA; PYISRPT; -. DR PhylomeDB; P15498; -. DR TreeFam; TF316171; -. DR PathwayCommons; P15498; -. DR Reactome; R-HSA-114604; GPVI-mediated activation cascade. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-193648; NRAGE signals death through JNK. DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization. DR Reactome; R-HSA-389359; CD28 dependent Vav1 pathway. DR Reactome; R-HSA-416482; G alpha (12/13) signalling events. DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling. DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-8980692; RHOA GTPase cycle. DR Reactome; R-HSA-9013149; RAC1 GTPase cycle. DR Reactome; R-HSA-9013404; RAC2 GTPase cycle. DR Reactome; R-HSA-9013408; RHOG GTPase cycle. DR Reactome; R-HSA-9027284; Erythropoietin activates RAS. DR Reactome; R-HSA-912631; Regulation of signaling by CBL. DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis. DR Reactome; R-HSA-9748787; Azathioprine ADME. DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR SignaLink; P15498; -. DR SIGNOR; P15498; -. DR BioGRID-ORCS; 7409; 13 hits in 1071 CRISPR screens. DR ChiTaRS; VAV1; human. DR EvolutionaryTrace; P15498; -. DR GenomeRNAi; 7409; -. DR Pharos; P15498; Tchem. DR PRO; PR:P15498; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P15498; protein. DR Bgee; ENSG00000141968; Expressed in granulocyte and 126 other tissues. DR ExpressionAtlas; P15498; baseline and differential. DR Genevisible; P15498; HS. DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; EXP:Reactome. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0140031; F:phosphorylation-dependent protein binding; IEA:Ensembl. DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; TAS:Reactome. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0006955; P:immune response; IEA:Ensembl. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0030593; P:neutrophil chemotaxis; IEA:Ensembl. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:Ensembl. DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IEA:Ensembl. DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0008361; P:regulation of cell size; IGI:UniProtKB. DR GO; GO:0043087; P:regulation of GTPase activity; IGI:UniProtKB. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro. DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome. DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome. DR CDD; cd00029; C1; 1. DR CDD; cd01223; PH_Vav; 1. DR CDD; cd00160; RhoGEF; 1. DR CDD; cd10405; SH2_Vav1; 1. DR CDD; cd11979; SH3_VAV1_1; 1. DR CDD; cd11976; SH3_VAV1_2; 1. DR Gene3D; 1.10.418.10; -; 1. DR Gene3D; 1.20.900.10; -; 1. DR Gene3D; 2.30.29.30; -; 1. DR Gene3D; 3.30.505.10; -; 1. DR IDEAL; IID00652; -. DR InterPro; IPR022613; CAMSAP-like_CH_dom. DR InterPro; IPR001715; CH-domain. DR InterPro; IPR036872; CH_dom_sf. DR InterPro; IPR035899; DBL_dom_sf. DR InterPro; IPR000219; DH-domain. DR InterPro; IPR001331; GDS_CDC24_CS. DR InterPro; IPR002219; PE/DAG-bd. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR037832; PH_Vav. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR003096; SM22_calponin. DR InterPro; IPR028530; Vav1. DR InterPro; IPR035879; VAV1_SH2. DR InterPro; IPR035730; VAV1_SH3_1. DR InterPro; IPR035729; VAV1_SH3_2. DR PANTHER; PTHR45818:SF2; PTHR45818:SF2; 1. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF11971; CAMSAP_CH; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00621; RhoGEF; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF00018; SH3_1; 2. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00452; SH3DOMAIN. DR PRINTS; PR00888; SM22CALPONIN. DR SMART; SM00109; C1; 1. DR SMART; SM00033; CH; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00325; RhoGEF; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00326; SH3; 2. DR SUPFAM; SSF47576; SSF47576; 1. DR SUPFAM; SSF48065; SSF48065; 1. DR SUPFAM; SSF50044; SSF50044; 1. DR SUPFAM; SSF55550; SSF55550; 1. DR PROSITE; PS50021; CH; 1. DR PROSITE; PS00741; DH_1; 1. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS50002; SH3; 2. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Guanine-nucleotide releasing factor; KW Metal-binding; Phosphoprotein; Proto-oncogene; Reference proteome; Repeat; KW SH2 domain; SH3 domain; Zinc; Zinc-finger. FT CHAIN 1..845 FT /note="Proto-oncogene vav" FT /id="PRO_0000080980" FT DOMAIN 1..119 FT /note="Calponin-homology (CH)" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT DOMAIN 194..373 FT /note="DH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062" FT DOMAIN 402..504 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 592..660 FT /note="SH3 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 671..765 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 782..842 FT /note="SH3 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT ZN_FING 515..564 FT /note="Phorbol-ester/DAG-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT MOD_RES 826 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15592455" FT MOD_RES 844 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P27870" FT VAR_SEQ 187..218 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_047563" FT VARIANT 739 FT /note="T -> M (in dbSNP:rs36097961)" FT /id="VAR_051997" FT MUTAGEN 529 FT /note="C->R: Abolishes transforming activity." FT /evidence="ECO:0000269|PubMed:2069873" FT MUTAGEN 696 FT /note="R->L: Loss of interaction with SYK." FT /evidence="ECO:0000269|PubMed:8986718" FT CONFLICT 264 FT /note="A -> P (in Ref. 6; CAA34383)" FT /evidence="ECO:0000305" FT CONFLICT 368 FT /note="Q -> R (in Ref. 5; BAG62721)" FT /evidence="ECO:0000305" FT CONFLICT 718 FT /note="I -> TV (in Ref. 6)" FT /evidence="ECO:0000305" FT HELIX 3..13 FT /evidence="ECO:0007829|PDB:6NF1" FT TURN 22..24 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 30..37 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 41..50 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 57..59 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 68..84 FT /evidence="ECO:0007829|PDB:6NF1" FT TURN 90..92 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 96..100 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 105..116 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 119..122 FT /evidence="ECO:0007829|PDB:6NF1" FT TURN 123..125 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 145..148 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 158..160 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 173..177 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 191..219 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 221..225 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 230..236 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 240..259 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 261..263 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 266..273 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 276..278 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 279..285 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 287..300 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 302..316 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 317..319 FT /evidence="ECO:0007829|PDB:6NF1" FT HELIX 322..325 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 328..333 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 336..345 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 350..389 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 390..392 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 397..400 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 403..412 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 420..437 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 440..448 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 449..451 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 452..456 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 458..460 FT /evidence="ECO:0007829|PDB:6NEW" FT TURN 461..463 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 469..475 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 481..488 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 489..506 FT /evidence="ECO:0007829|PDB:6NEW" FT TURN 509..512 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 513..515 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 518..521 FT /evidence="ECO:0007829|PDB:6NEW" FT TURN 530..532 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 538..540 FT /evidence="ECO:0007829|PDB:6NEW" FT STRAND 543..546 FT /evidence="ECO:0007829|PDB:6NEW" FT TURN 547..549 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 555..560 FT /evidence="ECO:0007829|PDB:6NEW" FT HELIX 666..668 FT /evidence="ECO:0007829|PDB:2CRH" FT STRAND 669..672 FT /evidence="ECO:0007829|PDB:2CRH" FT HELIX 678..684 FT /evidence="ECO:0007829|PDB:2CRH" FT TURN 685..687 FT /evidence="ECO:0007829|PDB:2CRH" FT STRAND 692..696 FT /evidence="ECO:0007829|PDB:2CRH" FT STRAND 700..702 FT /evidence="ECO:0007829|PDB:2LCT" FT STRAND 706..711 FT /evidence="ECO:0007829|PDB:2CRH" FT STRAND 714..719 FT /evidence="ECO:0007829|PDB:2CRH" FT STRAND 721..723 FT /evidence="ECO:0007829|PDB:2CRH" FT STRAND 726..730 FT /evidence="ECO:0007829|PDB:2CRH" FT STRAND 735..737 FT /evidence="ECO:0007829|PDB:2CRH" FT HELIX 738..745 FT /evidence="ECO:0007829|PDB:2CRH" FT HELIX 750..752 FT /evidence="ECO:0007829|PDB:2CRH" FT STRAND 754..756 FT /evidence="ECO:0007829|PDB:2LCT" FT STRAND 763..766 FT /evidence="ECO:0007829|PDB:2CRH" SQ SEQUENCE 845 AA; 98314 MW; AC3BC9736FD2F138 CRC64; MELWRQCTHW LIQCRVLPPS HRVTWDGAQV CELAQALRDG VLLCQLLNNL LPHAINLREV NLRPQMSQFL CLKNIRTFLS TCCEKFGLKR SELFEAFDLF DVQDFGKVIY TLSALSWTPI AQNRGIMPFP TEEESVGDED IYSGLSDQID DTVEEDEDLY DCVENEEAEG DEIYEDLMRS EPVSMPPKMT EYDKRCCCLR EIQQTEEKYT DTLGSIQQHF LKPLQRFLKP QDIEIIFINI EDLLRVHTHF LKEMKEALGT PGAANLYQVF IKYKERFLVY GRYCSQVESA SKHLDRVAAA REDVQMKLEE CSQRANNGRF TLRDLLMVPM QRVLKYHLLL QELVKHTQEA MEKENLRLAL DAMRDLAQCV NEVKRDNETL RQITNFQLSI ENLDQSLAHY GRPKIDGELK ITSVERRSKM DRYAFLLDKA LLICKRRGDS YDLKDFVNLH SFQVRDDSSG DRDNKKWSHM FLLIEDQGAQ GYELFFKTRE LKKKWMEQFE MAISNIYPEN ATANGHDFQM FSFEETTSCK ACQMLLRGTF YQGYRCHRCR ASAHKECLGR VPPCGRHGQD FPGTMKKDKL HRRAQDKKRN ELGLPKMEVF QEYYGLPPPP GAIGPFLRLN PGDIVELTKA EAEQNWWEGR NTSTNEIGWF PCNRVKPYVH GPPQDLSVHL WYAGPMERAG AESILANRSD GTFLVRQRVK DAAEFAISIK YNVEVKHIKI MTAEGLYRIT EKKAFRGLTE LVEFYQQNSL KDCFKSLDTT LQFPFKEPEK RTISRPAVGS TKYFGTAKAR YDFCARDRSE LSLKEGDIIK ILNKKGQQGW WRGEIYGRVG WFPANYVEED YSEYC //