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Vav 1 guanine nucleotide exchange factor
Protein VAV1 PDB 1k1z.png
PDB rendering based on 1k1z.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols VAV1 ; VAV
External IDs OMIM164875 MGI98923 HomoloGene3961 GeneCards: VAV1 Gene
RNA expression pattern
PBB GE VAV1 206219 s at tn.png
More reference expression data
Species Human Mouse
Entrez 7409 22324
Ensembl ENSG00000141968 ENSMUSG00000034116
UniProt P15498 P27870
RefSeq (mRNA) NM_001258206 NM_001163815
RefSeq (protein) NP_001245135 NP_001157287
Location (UCSC) Chr 19:
6.77 – 6.86 Mb
Chr 17:
57.28 – 57.33 Mb
PubMed search [1] [2]

Proto-oncogene vav is a protein that in humans is encoded by the VAV1 gene.[1]

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.[2]


VAV1 has been shown to interact with Ku70,[3] PLCG1,[4] Lymphocyte cytosolic protein 2,[5][6] Janus kinase 2,[7][8] SIAH2,[9] S100B,[10] Abl gene,[11] ARHGDIB,[12] SHB,[13] PIK3R1,[4][7] PRKCQ,[14] Grb2,[9][15][16][17] MAPK1,[15][17] Syk,[15][18][19] Linker of activated T cells,[20][21] Cbl gene[19][22] and EZH2.[23]


  1. ^ 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. doi:10.1126/science.279.5350.558. PMID 9438848. 
  2. ^ "Entrez Gene: VAV1 vav 1 oncogene". 
  3. ^ Romero, F; Dargemont C, Pozo F, Reeves W H, Camonis J, Gisselbrecht S, Fischer S (January 1996). "p95vav associates with the nuclear protein Ku-70". Mol. Cell. Biol. (UNITED STATES) 16 (1): 37–44. ISSN 0270-7306. PMC 230976. PMID 8524317. 
  4. ^ a b 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. (NETHERLANDS) 441 (3): 480–4. doi:10.1016/S0014-5793(98)01593-2. ISSN 0014-5793. PMID 9891995. 
  5. ^ Raab, M; da Silva A J, Findell P R, Rudd C E (February 1997). "Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2". Immunity (UNITED STATES) 6 (2): 155–64. doi:10.1016/S1074-7613(00)80422-7. ISSN 1074-7613. PMID 9047237. 
  6. ^ Onodera, H; Motto D G, Koretzky G A, Rothstein D M (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. (UNITED STATES) 271 (36): 22225–30. doi:10.1074/jbc.271.36.22225. ISSN 0021-9258. PMID 8703037. 
  7. ^ a b 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. (UNITED STATES) 272 (22): 14334–40. doi:10.1074/jbc.272.22.14334. ISSN 0021-9258. PMID 9162069. 
  8. ^ Matsuguchi, T; Inhorn R C, Carlesso N, Xu G, Druker B, Griffin J D (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. (ENGLAND) 14 (2): 257–65. ISSN 0261-4189. PMC 398079. PMID 7530656. 
  9. ^ a b 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. (UNITED STATES) 19 (5): 3798–807. ISSN 0270-7306. PMC 84217. PMID 10207103. 
  10. ^ Fackler, O T; Luo W, Geyer M, Alberts A S, Peterlin B M (June 1999). "Activation of Vav by Nef induces cytoskeletal rearrangements and downstream effector functions". Mol. Cell (UNITED STATES) 3 (6): 729–39. doi:10.1016/S1097-2765(01)80005-8. ISSN 1097-2765. PMID 10394361. 
  11. ^ Bassermann, Florian; Jahn Thomas, Miething Cornelius, Seipel Petra, Bai Ren-Yuan, Coutinho Sunita, Tybulewicz Victor L, Peschel Christian, Duyster Justus (April 2002). "Association of Bcr-Abl with the proto-oncogene Vav is implicated in activation of the Rac-1 pathway". J. Biol. Chem. (United States) 277 (14): 12437–45. doi:10.1074/jbc.M112397200. ISSN 0021-9258. PMID 11790798. 
  12. ^ Groysman, M; Russek C S, Katzav S (February 2000). "Vav, a GDP/GTP nucleotide exchange factor, interacts with GDIs, proteins that inhibit GDP/GTP dissociation". FEBS Lett. (NETHERLANDS) 467 (1): 75–80. doi:10.1016/S0014-5793(00)01121-2. ISSN 0014-5793. PMID 10664460. 
  13. ^ Lindholm, Cecilia K; Henriksson Maria L, Hallberg Bengt, Welsh Michael (July 2002). "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells". Eur. J. Biochem. (Germany) 269 (13): 3279–88. doi:10.1046/j.1432-1033.2002.03008.x. ISSN 0014-2956. PMID 12084069. 
  14. ^ Hehner, S P; Li-Weber M, Giaisi M, Dröge W, Krammer P H, Schmitz M L (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. (UNITED STATES) 164 (7): 3829–36. doi:10.4049/jimmunol.164.7.3829. ISSN 0022-1767. PMID 10725744. 
  15. ^ a b c Song, J S; Gomez J, Stancato L F, 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. (UNITED STATES) 271 (43): 26962–70. doi:10.1074/jbc.271.43.26962. ISSN 0021-9258. PMID 8900182. 
  16. ^ Ye, Z S; Baltimore D (Dec 1994). "Binding of Vav to Grb2 through dimerization of Src homology 3 domains". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 91 (26): 12629–33. doi:10.1073/pnas.91.26.12629. ISSN 0027-8424. PMC 45492. PMID 7809090. 
  17. ^ a b Lee, I S; 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. (NETHERLANDS) 401 (2–3): 133–7. doi:10.1016/S0014-5793(96)01456-1. ISSN 0014-5793. PMID 9013873. 
  18. ^ 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 (UNITED STATES) 5 (6): 591–604. doi:10.1016/S1074-7613(00)80273-3. ISSN 1074-7613. PMID 8986718. 
  19. ^ a b Bertagnolo, V; Marchisio M, Brugnoli F, Bavelloni A, Boccafogli L, Colamussi M L, Capitani S (April 2001). "Requirement of tyrosine-phosphorylated Vav for morphological differentiation of all-trans-retinoic acid-treated HL-60 cells". Cell Growth Differ. (United States) 12 (4): 193–200. ISSN 1044-9523. PMID 11331248. 
  20. ^ Paz, P E; 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. (England) 356 (Pt 2): 461–71. doi:10.1042/0264-6021:3560461. ISSN 0264-6021. PMC 1221857. PMID 11368773. 
  21. ^ Perez-Villar, Juan J; Whitney Gena S, Sitnick Mitchell T, Dunn Robert J, Venkatesan Srividhya, O'Day Kathleen, Schieven Gary L, Lin Tai-An, Kanner Steven B (August 2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry (United States) 41 (34): 10732–40. doi:10.1021/bi025554o. ISSN 0006-2960. PMID 12186560. 
  22. ^ Marengère, L E; Mirtsos C, Kozieradzki I, Veillette A, Mak T W, Penninger J M (July 1997). "Proto-oncoprotein Vav interacts with c-Cbl in activated thymocytes and peripheral T cells". J. Immunol. (UNITED STATES) 159 (1): 70–6. ISSN 0022-1767. PMID 9200440. 
  23. ^ 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. (UNITED STATES) 16 (6): 3066–73. ISSN 0270-7306. PMC 231301. PMID 8649418. 

Further reading[edit]