VAV1

VAV1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CRH, 2LCT, 2MC1, 2ROR, 3BJI, 3KY9
Identifiers
Aliases	VAV1, VAV, vav guanine nucleotide exchange factor 1
External IDs	OMIM: 164875; MGI: 98923; HomoloGene: 3961; GeneCards: VAV1; OMA:VAV1 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.3 Start 6,772,708 bp[1] End 6,857,366 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 D|17 29.76 cM Start 57,586,100 bp[2] End 57,635,031 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte monocyte blood spleen bone marrow cells lymph node appendix palpebral conjunctiva epithelium of nasopharynx trabecular bone Top expressed in superior surface of tongue gallbladder granulocyte thymus mesenteric lymph nodes interventricular septum spleen blood gastrula lumbar subsegment of spinal cord More reference expression data BioGPS More reference expression data
Gene ontology Molecular function guanyl-nucleotide exchange factor activity DNA-binding transcription factor activity metal ion binding protein binding phosphatidylinositol-4,5-bisphosphate 3-kinase activity phosphotyrosine residue binding Cellular component cytosol cell-cell junction plasma membrane Biological process regulation of cell size intracellular signal transduction Fc-gamma receptor signaling pathway involved in phagocytosis regulation of GTPase activity T cell costimulation neutrophil chemotaxis reactive oxygen species metabolic process platelet activation Fc-epsilon receptor signaling pathway positive regulation of GTPase activity T cell differentiation vascular endothelial growth factor receptor signaling pathway immune response phagocytosis positive regulation of apoptotic process integrin-mediated signaling pathway regulation of Rho protein signal transduction regulation of small GTPase mediated signal transduction positive regulation of natural killer cell mediated cytotoxicity T cell activation positive regulation of cell adhesion regulation of transcription, DNA-templated phosphatidylinositol phosphate biosynthetic process small GTPase mediated signal transduction G protein-coupled receptor signaling pathway positive regulation of protein kinase B signaling cytokine-mediated signaling pathway positive regulation of Ras protein signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7409 22324 Ensembl ENSG00000141968 ENSMUSG00000034116 UniProt P15498 P27870 RefSeq (mRNA) NM_001258206 NM_001258207 NM_005428 NM_001163815 NM_001163816 NM_011691 RefSeq (protein) NP_001245135 NP_001245136 NP_005419 NP_001157287 NP_001157288 NP_035821 Location (UCSC) Chr 19: 6.77 – 6.86 Mb Chr 17: 57.59 – 57.64 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Proto-oncogene vav is a protein that in humans is encoded by the VAV1 gene.[5]

Function

The protein encoded by this proto-oncogene is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. The protein is important in hematopoiesis, playing a role in T-cell and B-cell development and activation. This particular GEF has been identified as the specific binding partner of Nef proteins from HIV-1. Coexpression and binding of these partners initiates profound morphological changes, cytoskeletal rearrangements and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication.[6]

Interactions

VAV1 has been shown to interact with:

• ARHGDIB,[7]
• Abl gene,[8]
• Cbl gene[9][10]
• EZH2,[11]
• Grb2,[12][13][14][15]
• JAK2,[16][17]
• Ku70,[18]
• LAT,[19][20]
• LCP2,[21][22]
• MAPK1,[13][15]
• PIK3R1,[16][23]
• PLCG1,[23]
• PRKCQ,[24]
• S100B,[25]
• SHB,[26]
• SIAH2,[12] and
• Syk.[9][13][27]

References

1. GRCh38: Ensembl release 89: ENSG00000141968 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000034116 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Han J, Luby-Phelps K, Das B, Shu X, Xia Y, Mosteller RD, Krishna UM, Falck JR, White MA, Broek D (February 1998). "Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav". Science. 279 (5350): 558–60. Bibcode:1998Sci...279..558H. doi:10.1126/science.279.5350.558. PMID 9438848.
6. "Entrez Gene: VAV1 vav 1 oncogene".
7. Groysman M, Russek CS, Katzav S (February 2000). "Vav, a GDP/GTP nucleotide exchange factor, interacts with GDIs, proteins that inhibit GDP/GTP dissociation". FEBS Lett. 467 (1): 75–80. doi:10.1016/S0014-5793(00)01121-2. PMID 10664460. S2CID 40103095.
8. Bassermann F, Jahn T, Miething C, Seipel P, Bai RY, Coutinho S, Tybulewicz VL, Peschel C, Duyster J (April 2002). "Association of Bcr-Abl with the proto-oncogene Vav is implicated in activation of the Rac-1 pathway". J. Biol. Chem. 277 (14): 12437–45. doi:10.1074/jbc.M112397200. PMID 11790798.
9. Bertagnolo V, Marchisio M, Brugnoli F, Bavelloni A, Boccafogli L, Colamussi ML, Capitani S (April 2001). "Requirement of tyrosine-phosphorylated Vav for morphological differentiation of all-trans-retinoic acid-treated HL-60 cells". Cell Growth Differ. 12 (4): 193–200. PMID 11331248.
10. Marengère LE, Mirtsos C, Kozieradzki I, Veillette A, Mak TW, Penninger JM (July 1997). "Proto-oncoprotein Vav interacts with c-Cbl in activated thymocytes and peripheral T cells". J. Immunol. 159 (1): 70–6. doi:10.4049/jimmunol.159.1.70. PMID 9200440.
11. Hobert O, Jallal B, Ullrich A (June 1996). "Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression". Mol. Cell. Biol. 16 (6): 3066–73. doi:10.1128/MCB.16.6.3066. PMC 231301. PMID 8649418.
12. Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S, Varin-Blank N (May 1999). "hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways". Mol. Cell. Biol. 19 (5): 3798–807. doi:10.1128/MCB.19.5.3798. PMC 84217. PMID 10207103.
13. Song JS, Gomez J, Stancato LF, Rivera J (October 1996). "Association of a p95 Vav-containing signaling complex with the FcepsilonRI gamma chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex". J. Biol. Chem. 271 (43): 26962–70. doi:10.1074/jbc.271.43.26962. PMID 8900182.
14. Ye ZS, Baltimore D (Dec 1994). "Binding of Vav to Grb2 through dimerization of Src homology 3 domains". Proc. Natl. Acad. Sci. U.S.A. 91 (26): 12629–33. Bibcode:1994PNAS...9112629Y. doi:10.1073/pnas.91.26.12629. PMC 45492. PMID 7809090.
15. Lee IS, Liu Y, Narazaki M, Hibi M, Kishimoto T, Taga T (January 1997). "Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6". FEBS Lett. 401 (2–3): 133–7. doi:10.1016/s0014-5793(96)01456-1. PMID 9013873. S2CID 32632406.
16. Shigematsu H, Iwasaki H, Otsuka T, Ohno Y, Arima F, Niho Y (May 1997). "Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity". J. Biol. Chem. 272 (22): 14334–40. doi:10.1074/jbc.272.22.14334. PMID 9162069.
17. Matsuguchi T, Inhorn RC, Carlesso N, Xu G, Druker B, Griffin JD (January 1995). "Tyrosine phosphorylation of p95Vav in myeloid cells is regulated by GM-CSF, IL-3 and steel factor and is constitutively increased by p210BCR/ABL". EMBO J. 14 (2): 257–65. doi:10.1002/j.1460-2075.1995.tb06999.x. PMC 398079. PMID 7530656.
18. Romero F, Dargemont C, Pozo F, Reeves WH, Camonis J, Gisselbrecht S, Fischer S (January 1996). "p95vav associates with the nuclear protein Ku-70". Mol. Cell. Biol. 16 (1): 37–44. doi:10.1128/mcb.16.1.37. PMC 230976. PMID 8524317.
19. Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A (June 2001). "Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells". Biochem. J. 356 (Pt 2): 461–71. doi:10.1042/0264-6021:3560461. PMC 1221857. PMID 11368773.
20. Perez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K, Schieven GL, Lin TA, Kanner SB (August 2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry. 41 (34): 10732–40. doi:10.1021/bi025554o. PMID 12186560.
21. Raab M, da Silva AJ, Findell PR, Rudd CE (February 1997). "Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2". Immunity. 6 (2): 155–64. doi:10.1016/s1074-7613(00)80422-7. PMID 9047237.
22. Onodera H, Motto DG, Koretzky GA, Rothstein DM (September 1996). "Differential regulation of activation-induced tyrosine phosphorylation and recruitment of SLP-76 to Vav by distinct isoforms of the CD45 protein-tyrosine phosphatase". J. Biol. Chem. 271 (36): 22225–30. doi:10.1074/jbc.271.36.22225. PMID 8703037.
23. Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S (Dec 1998). "Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells". FEBS Lett. 441 (3): 480–4. doi:10.1016/s0014-5793(98)01593-2. PMID 9891995. S2CID 38371954.
24. Hehner SP, Li-Weber M, Giaisi M, Dröge W, Krammer PH, Schmitz ML (April 2000). "Vav synergizes with protein kinase C theta to mediate IL-4 gene expression in response to CD28 costimulation in T cells". J. Immunol. 164 (7): 3829–36. doi:10.4049/jimmunol.164.7.3829. PMID 10725744.
25. Fackler OT, Luo W, Geyer M, Alberts AS, Peterlin BM (June 1999). "Activation of Vav by Nef induces cytoskeletal rearrangements and downstream effector functions". Mol. Cell. 3 (6): 729–39. doi:10.1016/S1097-2765(01)80005-8. PMID 10394361.
26. Lindholm CK, Henriksson ML, Hallberg B, Welsh M (July 2002). "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells". Eur. J. Biochem. 269 (13): 3279–88. doi:10.1046/j.1432-1033.2002.03008.x. PMID 12084069.
27. Deckert M, Tartare-Deckert S, Couture C, Mustelin T, Altman A (Dec 1996). "Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product". Immunity. 5 (6): 591–604. doi:10.1016/s1074-7613(00)80273-3. PMID 8986718.

Further reading

• Romero F, Fischer S (1997). "Structure and function of vav". Cell. Signal. 8 (8): 545–53. doi:10.1016/S0898-6568(96)00118-0. PMID 9115846.
• Bustelo XR (2000). "Regulatory and Signaling Properties of the Vav Family". Mol. Cell. Biol. 20 (5): 1461–77. doi:10.1128/MCB.20.5.1461-1477.2000. PMC 85310. PMID 10669724.
• Geyer M, Fackler OT, Peterlin BM (2001). "Structure–function relationships in HIV-1 Nef". EMBO Rep. 2 (7): 580–5. doi:10.1093/embo-reports/kve141. PMC 1083955. PMID 11463741.
• Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (2004). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". J. Biosci. 28 (3): 323–35. doi:10.1007/BF02970151. PMID 12734410. S2CID 33749514.
• Anderson JL, Hope TJ (2005). "HIV accessory proteins and surviving the host cell". Current HIV/AIDS Reports. 1 (1): 47–53. doi:10.1007/s11904-004-0007-x. PMID 16091223. S2CID 34731265.
• Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects". Curr. HIV Res. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID 16454711.
• Katzav S (2007). "Flesh and blood: the story of Vav1, a gene that signals in hematopoietic cells but can be transforming in human malignancies". Cancer Lett. 255 (2): 241–54. doi:10.1016/j.canlet.2007.04.015. PMID 17590270.
• Bustelo XR, Barbacid M (1992). "Tyrosine phosphorylation of the vav proto-oncogene product in activated B cells". Science. 256 (5060): 1196–9. Bibcode:1992Sci...256.1196B. doi:10.1126/science.256.5060.1196. PMID 1375396. S2CID 35071104.
• Adams JM, Houston H, Allen J, Lints T, Harvey R (1992). "The hematopoietically expressed vav proto-oncogene shares homology with the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization". Oncogene. 7 (4): 611–8. PMID 1565462.
• Katzav S, Cleveland JL, Heslop HE, Pulido D (1991). "Loss of the amino-terminal helix-loop-helix domain of the vav proto-oncogene activates its transforming potential". Mol. Cell. Biol. 11 (4): 1912–20. doi:10.1128/MCB.11.4.1912. PMC 359873. PMID 2005887.
• Coppola J, Bryant S, Koda T, Conway D, Barbacid M (1991). "Mechanism of activation of the vav protooncogene". Cell Growth Differ. 2 (2): 95–105. PMID 2069873.
• Katzav S, Martin-Zanca D, Barbacid M (1989). "vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells". EMBO J. 8 (8): 2283–90. doi:10.1002/j.1460-2075.1989.tb08354.x. PMC 401160. PMID 2477241.
• Ramos-Morales F, Romero F, Schweighoffer F, Bismuth G, Camonis J, Tortolero M, Fischer S (1995). "The proline-rich region of Vav binds to Grb2 and Grb3-3". Oncogene. 11 (8): 1665–9. PMID 7478592.
• Weng WK, Jarvis L, LeBien TW (1995). "Signaling through CD19 activates Vav/mitogen-activated protein kinase pathway and induces formation of a CD19/Vav/phosphatidylinositol 3-kinase complex in human B cell precursors". J. Biol. Chem. 269 (51): 32514–21. doi:10.1016/S0021-9258(18)31664-8. PMID 7528218.
• Matsuguchi T, Inhorn RC, Carlesso N, Xu G, Druker B, Griffin JD (1995). "Tyrosine phosphorylation of p95Vav in myeloid cells is regulated by GM-CSF, IL-3 and steel factor and is constitutively increased by p210BCR/ABL". EMBO J. 14 (2): 257–65. doi:10.1002/j.1460-2075.1995.tb06999.x. PMC 398079. PMID 7530656.
• Uddin S, Katzav S, White MF, Platanias LC (1995). "Insulin-dependent tyrosine phosphorylation of the vav protooncogene product in cells of hematopoietic origin". J. Biol. Chem. 270 (13): 7712–6. doi:10.1074/jbc.270.13.7712. PMID 7535775.
• Machide M, Mano H, Todokoro K (1995). "Interleukin 3 and erythropoietin induce association of Vav with Tec kinase through Tec homology domain". Oncogene. 11 (4): 619–25. PMID 7651724.
• Clevenger CV, Ngo W, Sokol DL, Luger SM, Gewirtz AM (1995). "Vav is necessary for prolactin-stimulated proliferation and is translocated into the nucleus of a T-cell line". J. Biol. Chem. 270 (22): 13246–53. doi:10.1074/jbc.270.22.13246. PMID 7768923.
• Katzav S, Sutherland M, Packham G, Yi T, Weiss A (1995). "The protein tyrosine kinase ZAP-70 can associate with the SH2 domain of proto-Vav". J. Biol. Chem. 269 (51): 32579–85. doi:10.1016/S0021-9258(18)31673-9. PMID 7798261.
• Ye ZS, Baltimore D (1995). "Binding of Vav to Grb2 through dimerization of Src homology 3 domains". Proc. Natl. Acad. Sci. U.S.A. 91 (26): 12629–33. Bibcode:1994PNAS...9112629Y. doi:10.1073/pnas.91.26.12629. PMC 45492. PMID 7809090.