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VAV3 (vav 3 guanine nucleotide exchange factor)

Written2010-08Leah Lyons, Kerry L Burnstein
Nova Southeastern University, College of Medical Sciences, Department of Physiology, Florida, USA (LL); University of Miami, Miller School of Medicine, Department of Molecular, Cellular Pharmacology, Miami, Florida, USA (KLB)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesvav 3 oncogene
vav 3 guanine nucleotide exchange factor
Other aliasFLJ40431
HGNC (Hugo) VAV3
LocusID (NCBI) 10451
Atlas_Id 42782
Location 1p13.3  [Link to chromosome band 1p13]
Location_base_pair Starts at 108113782 and ends at 108231126 bp from pter ( according to hg19-Feb_2009)  [Mapping VAV3.png]
Local_order VAV3 maps to the minus strand of chromosome 1.
Fusion genes
(updated 2016)
FOXO4 (Xq13.1) / VAV3 (1p13.3)VAV3 (1p13.3) / DAB1 (1p32.2)VAV3 (1p13.3) / RGL1 (1q25.3)
VAV3 (1p13.3) / VAV3 (1p13.3)VAV3 (1p13.3) / WARS2 (1p12)VAV3 (1p13.3) / ZHX2 (8q24.13)

DNA/RNA

 
  Figure 1. Upper figure shows gene organization for the alpha (canonical) isoform (ID NM 006113.4) and isoform 2 (ID NM 001079874.1) which corresponds to the 287 amino acid Vav3.1 transcript variant (described below). Lower panel illustrates neighboring genes. Figures adapted from NCBI Gene database.
Description The VAV3 gene is comprised of 27 exons spanning 393.7 kb on chromosome 1p13.3. It is located on the reverse strand 108113782 bp from pter -108507545 basepairs from pter.
Transcription There are two known isoforms produced by alternative splicing and a third transcript thought to be derived from alternate promoter usage (Vav3.1). The alpha isoform is the canonical sequence and is derived from the full 27 exons. Isoform beta differs in the N terminus from the alpha isoform as follows: The residues 1-107 in the alpha isoform, MEPWKQCAQW...DLFDVRDFGK, are replaced by MQLPDCPCRAHLP in the beta isoform. The beta isoform is produced from a unique exon 1 spliced to exons 4-27 (Maier et al., 2005). Additionally, a transcript variant encoding only the C terminal SH3 SH2 SH3 domains has been identified and is known as Vav3.1. This variant is derived from a unique exon 18 and exons 19-27 (Maier et al., 2005) and is thought to be produced either by alternative splicing or through alternate promoter usage. The Vav3 mRNA consists of a 54 base pair 5 prime UTR and a 2171 basepair 3 prime UTR (Trenkle et al., 2000). The promoter region of Vav3 contains predicted binding sites for the following transcription factors: STAT3, c-MYB, LMO2, GATA-1, GCNF-2, E47, GCNF-1, PAX-5, POU2F1, and FOXO1A (information obtained from data deposited in Genecard database through use of SABiosciences' text mining application and the UCSC genome browser). It is worth mentioning that the gene locus is complex and could potentially produce up to 13 different isoforms resulting from alternative splicing and alternate promoter usage (Thierry-Mieg and Thierry-Mieg, 2006).
Vav3 can be modified posttranslationally by phosphorylation. Phosphorylation site prediction identifies phosphorylation sites at T131, S134, Y141, Y173, S511, T606 and Y797. Sites residing in the N terminal region have been shown to regulate activation of Vav3 GEF function (Movilla and Bustelo, 1999). In the unphosphorylated state, the GEF domain is prevented from physical association with Rho proteins by the Vav3 N terminal domains. These domains (calponin homology and acidic domains) form an autoinhibitory loop via intramolecular interactions. Vav3 is recruited via its SH2 domain to phosphotyrosine residues on interacting proteins, including activated growth factor receptors. Once bound to active growth factor receptors, or other molecules containing intrinsic tyrosine kinase activity, Vav3 becomes tyrosine phosphorylated (Movilla and Bustelo, 1999; Bustelo, 2002; Zugaza et al., 2002). Tyrosine phosphorylation of Vav3 results in a conformational change that relieves the autoinhibition, thus activating the GEF function by allowing access of Rho proteins to the GEF domain (Movilla and Bustelo, 1999; Yu et al., 2010). Tyrosine 173 in particular is a critical residue in this process (Llorca et al., 2005; Yu et al., 2010). Consistent with an autoinhibitory role of the N terminal regions, removal of both the calponin homology and the acidic domains results in constitutive activation of Vav3 GEF function (Movilla and Bustelo, 1999; Zeng et al., 2000; Zugaza et al., 2002).

Protein

 
  Figure 2. Functional domains of Vav3 proteins and their relative positions. Abbreviations are as follows: CH: calponin homology, AD: acidic domain, DH: DBL homology, PH: pleckstrin homology, CRD: cysteine rich domain, SH3: Src homology 3 and SH2: Src homology 2.
Description The VAV3 gene encodes a 847 amino acid mature protein. The mature protein has a molecular mass of approximately 98 kDa and functions as a guanine nucleotide exchange factor (GEF) for members of the Rho family of small GTPases (Movilla and Bustelo,1999; Trenkle et al., 2000). Vav3 is structurally complex consisting of multiple functional domains. These domains consist sequentially of a single calponin homology domain encompassing residues 1-119, an acidic domain, a DBL homology domain which confers GEF function. The DBL homology domain is comprised of residues 192-371, followed by a pleckstrin homology domain, spanning residues 400-502 a cysteine rich domain (also termed a zinc finger domain) comprising residues 513-562 and two SH3 domains flanking a single SH2 domain. The SH3-SH2-SH3 cassette comprises the C terminal portion of Vav3 and extends from the N terminal SH3 domain (residues 592-660), to the C terminal SH3 domain (residues 788-847) and includes the intervening SH2 domain (residues 672-766) (Trenkle et al., 2000). Residing within the N terminal SH3 domain is a proline rich region which may be involved in facilitating intramolecular interactions between the C terminal regions (our unpublished observations).
 
  Figure 3. Schematic showing inactive (top panel) and active (bottom panel) conformations of Vav3. Movement of the N terminal regions to allow RhoGTPase access to the DH domain is regulated by phosphorylation events.
Expression Vav3 is broadly expressed but with highest levels in cells of hematopoietic lineages (Trenkle et al., 2000).
Localisation Vav3 is located predominantly in the cytoplasm, and is often recruited to the membrane upon activation of the various cell surface receptors that are coupled to Vav3 phosphorylation (Zeng et al., 2000).
Function Vav3 functions as a guanine nucleotide exchange factor mediating activation of Rho GTPases by stabilization of the nucleotide free state of Rho proteins. Specifically, Vav3 has been shown to act as a GEF for RhoA, RhoG and RAC1 (Movilla and Bustelo, 1999; Zugaza et al., 2002). Vav3 couples the activation of growth factor type receptors such as IGFR, EGFR, PDGFR, insulin receptor and ROS receptor (Zeng et al., 2000) to downstream signaling molecules including but not limited to Jun kinase, NFKappa B, MAPK and Stat pathways (Moores et al., 2000; Sachdev et al., 2002). More recently, Vav3 activation by Eph Receptors has been demonstrated (Fang et al., 2008) and a large number of studies have shown the activation of Vav3 upon integrin signaling (Gakidis et al., 2004; Faccio et al., 2005; Pearce et al., 2007; Sindrilaru et al., 2009).
Vav3 is implicated in B cell induced antigen presentation to T cells (Malhotra et al., 2009) and mediates both B and T cell signaling events and alteration of macrophage morphology (Sindrilaru et al., 2009). Additionally, protein interactions with the C terminal SH3 SH2, SH3 cassette have revealed roles in scaffolding through adaptor like actions (Bustelo, 2001; Yabana and Shibuya, 2002).

Additional functions of Vav3 in distinct tissues are listed below.
Nervous system: NGF-induced neurite outgrowth in PC12 cells requires Vav3-mediated activation of Rac. This process involves P13K activation which occurs upstream of Vav3 (Aoki et al., 2005). Vav3 is also important for neuronal migration during development (Khodosevich et al., 2009). Additionally, Vav3 knockout mice show defects in Purkinje cell dendrite branching, granule cell migration and survival. Functionally the animals show deficiencies in motor coordination and gaiting consistent with a role for Vav3 in neuronal guidance, cerebellar development and function (Quevedo et al., 2010).
Skeletal system: Studies in osteoclasts support a role for Vav3 in mediating proper bone deposition. Specifically, Vav3 deficient osteoclasts exhibit abnormalities in actin cytoskeletal rearrangements, cell spreading, and resorptive activities. Consistent with the actions of Vav3 on integrin signaling, the osteoclast defects were found to be due to impaired integrin engagement. Further, Vav3 deficient mice have increased bone density and are refractory to PTH-mediated bone resorption (Faccio et al., 2005).
Cardiovascular system: An important role for Vav3 in maintaining proper cardiovascular homeostasis was suggested by experiments performed in Vav3 null mice. These mice exhibited many symptoms of cardiovascular dysfunction including tachycardia, hypertension and cardiovascular remodeling. Consistent with these symptoms, the mice also exhibited a high degree of sympathetic tone including elevated circulating levels of catecholamines and renin-angiotensin-aldosterone hyperactivity, resulting in progressive loss of both cardiovascular and renal homeostasis (Sauzeau et al., 2006).
Vascular smooth muscle: Vav3 is both necessary and sufficient for rat vascular smooth muscle cell proliferation. These effects occur through a Rac-1 dependent mechanism, involving the effector Pak 1 (Toumaniantz et al., 2010).
Platelets: Consistent with a role for Vav3 in mediating integrin-based responses, Vav3 and Vav1 together are required for collagen exposure-mediated PLC activation in platelets. This signaling pathway occurs through the major platelet integrin alphaIIbbetaIII (Pearce et al., 2004).
Angiogenesis: Mice deficient in both Vav3 and Vav2 show reduced endothelial migration in response to the presence of tumor cells. Additionally Vav2 and Vav3 were found to be necessary and sufficient for Eph A receptor-mediated angiogenesis both in vitro and in vivo (Hunter et al., 2006).

Homology Vav3 is conserved among vertebrates including dog, cow, mouse, rat, chicken and zebrafish, and has been shown to be present and conserved in Drosophila melanogaster (Movilla and Bustelo, 1999; Couceiro et al., 2005). Vav3 displays over 50% amino acid identity with other members of the Vav family of GEFS, Vav1 and Vav2 which have a similar arrangement of functional domains and regulation (Trenkle et al., 2000).

Mutations

Note None described. SNP analysis has revealed several genetic polymorphisms, the implications of which remain unclear. The single nucleotide polymorphisms resulting in differing amino acid sequence are as follows: residue 139, D to N, residue 298, T to S, residue 616 P to S, and residue Q to H. There are multiple SNPS residing in both the 3'UTR and 5'UTR regions. The implications of these are not known.

Implicated in

Note
  
Entity Prostate cancer
Note Vav3 mRNA and protein are up-regulated during progression of human prostate cancer cells to androgen independence in cell culture and in vivo experimental studies (Lyons and Burnstein, 2006; Lyons et al., 2008). Further, the importance of this upregulation to the disease process has been elucidated by more recent studies showing that Vav3 mRNA is up-regulated in prostate cancer tumor specimens obtained from men undergoing androgen deprivation therapy compared to levels in primary tumors (Holzbeierlein et al., 2004; Best et al., 2005; data deposited in public databases). Vav3 protein is overexpressed (relative to benign tissue) in almost one-third of prostate cancer tumor specimens (Dong et al., 2006).
Additionally, Vav3 mRNA is up-regulated in androgen independent tumors in the Nkx3.1; Pten mouse model of prostate cancer (Banach-Petrosky et al., 2007; Ouyang et al., 2008) and targeted expression of a constitutively active form of Vav3 in prostate epithelium of transgenic mice leads to overactivity of the androgen receptor signaling axis and adenocarcinoma (Liu et al., 2008). Mechanistic studies show that Vav3 stimulates ligand independent androgen receptor activation by a GEF-dependent mechanism that requires the Rho GTPase, Rac 1 in prostate cancer cells (Lyons et al., 2008). Additionally, Vav3 enhances androgen receptor transcriptional activity in the presence of low concentrations of androgen through a GEF independent pathway that requires the Vav3 PH domain (Lyons and Burnstein, 2006).
  
  
Entity Breast cancer
Note Lee et al. reported that 81% of human breast cancer specimens exhibited higher levels of Vav3 compared to benign tissue (Lee et al., 2008). In addition, Vav3 enhances the transcriptional activity of the estrogen receptor in a GEF dependent manner (Lee et al., 2008).
  
  
Entity Gastric cancer
Note Downregulation of RUNX3, a member of the runt domain-containing family of transcription factors that has tumor suppressive actions, has been implicated in promoting human gastric carcinogenesis. Silencing of RUNX3 expression via methylation was found in 75% of primary tumors and 100% of gastric metastasis. Stable reexpression of RUNX3 strongly inhibited peritoneal metastases. Further analysis suggested that Runx3 expression resulted in the downregulation of a number of genes including Vav3 thereby providing a potential line between Vav3 expression and gastric malignancy (Sakakura et al., 2005).
  
  
Entity Hepatocellular carcinoma
Note Vav3.1 was down regulated in HepG2 cells in response to treatment with the hepatocellular carcinoma chemotherapeutic triterpenoid agent astragoloside. Downregulation of Vav3.1 was highly correlated with a decrease in malignant transformation, suggesting a role for Vav3.1 in the antitumor actions of astragoloside (Shen et al., 1997).
  
  
Entity Glioblastoma
Note Vav3 is upregulated in glioblastoma as compared to nonneoplastic or lower grade gliomas. Down regulation of Vav3 by siRNA reduced glioblastoma invasion and migration. Further upregulation of Vav3 was shown to be an indicator of poor patient survival (Salhia et al., 2008).
  
  
Entity Tumor growth and angiogenesis
Note A role for Vav3 in promoting tumor growth and angiogensis has been revealed through studies using mice deficient in both Vav2 and Vav3 (Brantley-Sieders et al., 2009). Vav2, Vav3 knockout mice transplanted with B16 melanoma or Lewis lung carcinoma cells showed decreases in tumor growth, tumor survival and neovascularization of tumors as compared to wild type control mice. The reduction in vascularization and tumor growth was found to be secondary to a reduction in endothelial cell migration (Brantley-Sieders et al., 2009).
  
  
Entity Type 1 diabetes mellitus
Note Alteration in Vav3 expression may be an etiological factor in the development of beta islet cell destruction characteristic of type 1 diabetes (Fraser et al., 2010).
  

Bibliography

Local phosphatidylinositol 3,4,5-trisphosphate accumulation recruits Vav2 and Vav3 to activate Rac1/Cdc42 and initiate neurite outgrowth in nerve growth factor-stimulated PC12 cells.
Aoki K, Nakamura T, Fujikawa K, Matsuda M.
Mol Biol Cell. 2005 May;16(5):2207-17. Epub 2005 Feb 23.
PMID 15728722
 
Prolonged exposure to reduced levels of androgen accelerates prostate cancer progression in Nkx3.1; Pten mutant mice.
Banach-Petrosky W, Jessen WJ, Ouyang X, Gao H, Rao J, Quinn J, Aronow BJ, Abate-Shen C.
Cancer Res. 2007 Oct 1;67(19):9089-96.
PMID 17909013
 
Molecular alterations in primary prostate cancer after androgen ablation therapy.
Best CJ, Gillespie JW, Yi Y, Chandramouli GV, Perlmutter MA, Gathright Y, Erickson HS, Georgevich L, Tangrea MA, Duray PH, Gonzalez S, Velasco A, Linehan WM, Matusik RJ, Price DK, Figg WD, Emmert-Buck MR, Chuaqui RF.
Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):6823-34.
PMID 16203770
 
Host deficiency in Vav2/3 guanine nucleotide exchange factors impairs tumor growth, survival, and angiogenesis in vivo.
Brantley-Sieders DM, Zhuang G, Vaught D, Freeman T, Hwang Y, Hicks D, Chen J.
Mol Cancer Res. 2009 May;7(5):615-23. Epub 2009 May 12.
PMID 19435813
 
Vav proteins, adaptors and cell signaling.
Bustelo XR.
Oncogene. 2001 Oct 1;20(44):6372-81. (REVIEW)
PMID 11607839
 
Phylogenetic conservation of the regulatory and functional properties of the Vav oncoprotein family.
Couceiro JR, Martin-Bermudo MD, Bustelo XR.
Exp Cell Res. 2005 Aug 15;308(2):364-80.
PMID 15950967
 
Vav3 oncogene is overexpressed and regulates cell growth and androgen receptor activity in human prostate cancer.
Dong Z, Liu Y, Lu S, Wang A, Lee K, Wang LH, Revelo M, Lu S.
Mol Endocrinol. 2006 Oct;20(10):2315-25. Epub 2006 Jun 8.
PMID 16762975
 
Vav3 regulates osteoclast function and bone mass.
Faccio R, Teitelbaum SL, Fujikawa K, Chappel J, Zallone A, Tybulewicz VL, Ross FP, Swat W.
Nat Med. 2005 Mar;11(3):284-90. Epub 2005 Feb 13.
PMID 15711558
 
Identification and functional analysis of phosphorylated tyrosine residues within EphA2 receptor tyrosine kinase.
Fang WB, Brantley-Sieders DM, Hwang Y, Ham AJ, Chen J.
J Biol Chem. 2008 Jun 6;283(23):16017-26. Epub 2008 Apr 3.
PMID 18387945
 
Nonobese diabetic congenic strain analysis of autoimmune diabetes reveals genetic complexity of the Idd18 locus and identifies Vav3 as a candidate gene.
Fraser HI, Dendrou CA, Healy B, Rainbow DB, Howlett S, Smink LJ, Gregory S, Steward CA, Todd JA, Peterson LB, Wicker LS.
J Immunol. 2010 May 1;184(9):5075-84. Epub 2010 Apr 2.
PMID 20363978
 
Vav GEFs are required for beta2 integrin-dependent functions of neutrophils.
Gakidis MA, Cullere X, Olson T, Wilsbacher JL, Zhang B, Moores SL, Ley K, Swat W, Mayadas T, Brugge JS.
J Cell Biol. 2004 Jul 19;166(2):273-82. Epub 2004 Jul 12.
PMID 15249579
 
Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance.
Holzbeierlein J, Lal P, LaTulippe E, Smith A, Satagopan J, Zhang L, Ryan C, Smith S, Scher H, Scardino P, Reuter V, Gerald WL.
Am J Pathol. 2004 Jan;164(1):217-27.
PMID 14695335
 
Essential role of Vav family guanine nucleotide exchange factors in EphA receptor-mediated angiogenesis.
Hunter SG, Zhuang G, Brantley-Sieders D, Swat W, Cowan CW, Chen J.
Mol Cell Biol. 2006 Jul;26(13):4830-42.
PMID 16782872
 
Major signaling pathways in migrating neuroblasts.
Khodosevich K, Seeburg PH, Monyer H.
Front Mol Neurosci. 2009;2:7. Epub 2009 Jul 24.
PMID 19668709
 
Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer.
Lee K, Liu Y, Mo JQ, Zhang J, Dong Z, Lu S.
BMC Cancer. 2008 Jun 2;8:158.
PMID 18518979
 
Targeted overexpression of vav3 oncogene in prostatic epithelium induces nonbacterial prostatitis and prostate cancer.
Liu Y, Mo JQ, Hu Q, Boivin G, Levin L, Lu S, Yang D, Dong Z, Lu S.
Cancer Res. 2008 Aug 1;68(15):6396-406.
PMID 18676865
 
Global conformational rearrangements during the activation of the GDP/GTP exchange factor Vav3.
Llorca O, Arias-Palomo E, Zugaza JL, Bustelo XR.
EMBO J. 2005 Apr 6;24(7):1330-40. Epub 2005 Mar 10.
PMID 15775967
 
Vav3, a Rho GTPase guanine nucleotide exchange factor, increases during progression to androgen independence in prostate cancer cells and potentiates androgen receptor transcriptional activity.
Lyons LS, Burnstein KL.
Mol Endocrinol. 2006 May;20(5):1061-72. Epub 2005 Dec 29.
PMID 16384856
 
Ligand-independent activation of androgen receptors by Rho GTPase signaling in prostate cancer.
Lyons LS, Rao S, Balkan W, Faysal J, Maiorino CA, Burnstein KL.
Mol Endocrinol. 2008 Mar;22(3):597-608. Epub 2007 Dec 13.
PMID 18079321
 
Construction and analysis of tag single nucleotide polymorphism maps for six human-mouse orthologous candidate genes in type 1 diabetes.
Maier LM, Smyth DJ, Vella A, Payne F, Cooper JD, Pask R, Lowe C, Hulme J, Smink LJ, Fraser H, Moule C, Hunter KM, Chamberlain G, Walker N, Nutland S, Undlien DE, Ronningen KS, Guja C, Ionescu-Tirgoviste C, Savage DA, Strachan DP, Peterson LB, Todd JA, Wicker LS, Twells RC.
BMC Genet. 2005 Feb 18;6:9.
PMID 15720714
 
B cell antigen receptor endocytosis and antigen presentation to T cells require Vav and dynamin.
Malhotra S, Kovats S, Zhang W, Coggeshall KM.
J Biol Chem. 2009 Sep 4;284(36):24088-97. Epub 2009 Jul 8.
PMID 19586920
 
Vav family proteins couple to diverse cell surface receptors.
Moores SL, Selfors LM, Fredericks J, Breit T, Fujikawa K, Alt FW, Brugge JS, Swat W.
Mol Cell Biol. 2000 Sep;20(17):6364-73.
PMID 10938113
 
Biological and regulatory properties of Vav-3, a new member of the Vav family of oncoproteins.
Movilla N, Bustelo XR.
Mol Cell Biol. 1999 Nov;19(11):7870-85.
PMID 10523675
 
Activator protein-1 transcription factors are associated with progression and recurrence of prostate cancer.
Ouyang X, Jessen WJ, Al-Ahmadie H, Serio AM, Lin Y, Shih WJ, Reuter VE, Scardino PT, Shen MM, Aronow BJ, Vickers AJ, Gerald WL, Abate-Shen C.
Cancer Res. 2008 Apr 1;68(7):2132-44.
PMID 18381418
 
Vav family proteins are required for optimal regulation of PLCgamma2 by integrin alphaIIbbeta3.
Pearce AC, McCarty OJ, Calaminus SD, Vigorito E, Turner M, Watson SP.
Biochem J. 2007 Feb 1;401(3):753-61.
PMID 17054426
 
Vav1 and vav3 have critical but redundant roles in mediating platelet activation by collagen.
Pearce AC, Senis YA, Billadeau DD, Turner M, Watson SP, Vigorito E.
J Biol Chem. 2004 Dec 24;279(52):53955-62. Epub 2004 Sep 27.
PMID 15456756
 
Vav3-deficient mice exhibit a transient delay in cerebellar development.
Quevedo C, Sauzeau V, Menacho-Marquez M, Castro-Castro A, Bustelo XR.
Mol Biol Cell. 2010 Mar;21(6):1125-39. Epub 2010 Jan 20.
PMID 20089829
 
Distinct role of phosphatidylinositol 3-kinase and Rho family GTPases in Vav3-induced cell transformation, cell motility, and morphological changes.
Sachdev P, Zeng L, Wang LH.
J Biol Chem. 2002 May 17;277(20):17638-48. Epub 2002 Mar 7.
PMID 11884391
 
Possible involvement of RUNX3 silencing in the peritoneal metastases of gastric cancers.
Sakakura C, Hasegawa K, Miyagawa K, Nakashima S, Yoshikawa T, Kin S, Nakase Y, Yazumi S, Yamagishi H, Okanoue T, Chiba T, Hagiwara A.
Clin Cancer Res. 2005 Sep 15;11(18):6479-88.
PMID 16166423
 
The guanine nucleotide exchange factors trio, Ect2, and Vav3 mediate the invasive behavior of glioblastoma.
Salhia B, Tran NL, Chan A, Wolf A, Nakada M, Rutka F, Ennis M, McDonough WS, Berens ME, Symons M, Rutka JT.
Am J Pathol. 2008 Dec;173(6):1828-38. Epub 2008 Nov 13.
PMID 19008376
 
Vav3 proto-oncogene deficiency leads to sympathetic hyperactivity and cardiovascular dysfunction.
Sauzeau V, Sevilla MA, Rivas-Elena JV, de Alava E, Montero MJ, Lopez-Novoa JM, Bustelo XR.
Nat Med. 2006 Jul;12(7):841-5. Epub 2006 Jun 11.
PMID 16767097
 
Correlation between hypomethylation of c-myc and c-N-ras oncogenes and pathological changes in human hepatocellular carcinoma.
Shen L, Qui D, Fang J.
Zhonghua Zhong Liu Za Zhi. 1997 May;19(3):173-6.
PMID 10920889
 
Wound healing defect of Vav3-/- mice due to impaired {beta}2-integrin-dependent macrophage phagocytosis of apoptotic neutrophils.
Sindrilaru A, Peters T, Schymeinsky J, Oreshkova T, Wang H, Gompf A, Mannella F, Wlaschek M, Sunderkotter C, Rudolph KL, Walzog B, Bustelo XR, Fischer KD, Scharffetter-Kochanek K.
Blood. 2009 May 21;113(21):5266-76. Epub 2009 Jan 15.
PMID 19147786
 
AceView: a comprehensive cDNA-supported gene and transcripts annotation.
Thierry-Mieg D, Thierry-Mieg J.
Genome Biol. 2006;7 Suppl 1:S12.1-14. Epub 2006 Aug 7.
PMID 16925834
 
The Rho protein exchange factor Vav3 regulates vascular smooth muscle cell proliferation and migration.
Toumaniantz G, Ferland-McCollough D, Cario-Toumaniantz C, Pacaud P, Loirand G.
Cardiovasc Res. 2010 Apr 1;86(1):131-40. Epub 2009 Dec 7.
PMID 19969623
 
Major transcript variants of VAV3, a new member of the VAV family of guanine nucleotide exchange factors.
Trenkle T, McClelland M, Adlkofer K, Welsh J.
Gene. 2000 Mar 7;245(1):139-49.
PMID 10713454
 
Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity.
Yabana N, Shibuya M.
Oncogene. 2002 Oct 31;21(50):7720-9.
PMID 12400014
 
Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1.
Yu B, Martins IR, Li P, Amarasinghe GK, Umetani J, Fernandez-Zapico ME, Billadeau DD, Machius M, Tomchick DR, Rosen MK.
Cell. 2010 Jan 22;140(2):246-56.
PMID 20141838
 
Vav3 mediates receptor protein tyrosine kinase signaling, regulates GTPase activity, modulates cell morphology, and induces cell transformation.
Zeng L, Sachdev P, Yan L, Chan JL, Trenkle T, McClelland M, Welsh J, Wang LH.
Mol Cell Biol. 2000 Dec;20(24):9212-24.
PMID 11094073
 
Structural determinants for the biological activity of Vav proteins.
Zugaza JL, Lopez-Lago MA, Caloca MJ, Dosil M, Movilla N, Bustelo XR.
J Biol Chem. 2002 Nov 22;277(47):45377-92. Epub 2002 Sep 12.
PMID 12228230
 

Citation

This paper should be referenced as such :
Lyons, L ; Burnstein, KL
VAV3 (vav 3 guanine nucleotide exchange factor)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(5):436-440.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/VAV3ID42782ch1p13.html


External links

Nomenclature
HGNC (Hugo)VAV3   12659
Cards
AtlasVAV3ID42782ch1p13
Entrez_Gene (NCBI)VAV3  10451  vav guanine nucleotide exchange factor 3
Aliases
GeneCards (Weizmann)VAV3
Ensembl hg19 (Hinxton)ENSG00000134215 [Gene_View]  chr1:108113782-108231126 [Contig_View]  VAV3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000134215 [Gene_View]  chr1:108113782-108231126 [Contig_View]  VAV3 [Vega]
ICGC DataPortalENSG00000134215
TCGA cBioPortalVAV3
AceView (NCBI)VAV3
Genatlas (Paris)VAV3
WikiGenes10451
SOURCE (Princeton)VAV3
Genetics Home Reference (NIH)VAV3
Genomic and cartography
GoldenPath hg19 (UCSC)VAV3  -     chr1:108113782-108231126 -  1p13.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)VAV3  -     1p13.3   [Description]    (hg38-Dec_2013)
EnsemblVAV3 - 1p13.3 [CytoView hg19]  VAV3 - 1p13.3 [CytoView hg38]
Mapping of homologs : NCBIVAV3 [Mapview hg19]  VAV3 [Mapview hg38]
OMIM605541   
Gene and transcription
Genbank (Entrez)AF035442 AF067817 AF118886 AF118887 AI304566
RefSeq transcript (Entrez)NM_001079874 NM_006113
RefSeq genomic (Entrez)NC_000001 NC_018912 NT_032977 NW_004929290
Consensus coding sequences : CCDS (NCBI)VAV3
Cluster EST : UnigeneHs.267659 [ NCBI ]
CGAP (NCI)Hs.267659
Alternative Splicing GalleryENSG00000134215
Gene ExpressionVAV3 [ NCBI-GEO ]   VAV3 [ EBI - ARRAY_EXPRESS ]   VAV3 [ SEEK ]   VAV3 [ MEM ]
Gene Expression Viewer (FireBrowse)VAV3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10451
GTEX Portal (Tissue expression)VAV3
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UKW4   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UKW4  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UKW4
Splice isoforms : SwissVarQ9UKW4
PhosPhoSitePlusQ9UKW4
Domaine pattern : Prosite (Expaxy)CH (PS50021)    DH_1 (PS00741)    DH_2 (PS50010)    PH_DOMAIN (PS50003)    SH2 (PS50001)    SH3 (PS50002)    ZF_DAG_PE_1 (PS00479)    ZF_DAG_PE_2 (PS50081)   
Domains : Interpro (EBI)CAMSAP_CH    CH-domain    DH-domain    GDS_CDC24_CS    PE/DAG-bd    PH_dom-like    PH_domain    SH2    SH3_2    SH3_domain    SM22_calponin    Vav   
Domain families : Pfam (Sanger)C1_1 (PF00130)    CAMSAP_CH (PF11971)    PH (PF00169)    RhoGEF (PF00621)    SH2 (PF00017)    SH3_2 (PF07653)   
Domain families : Pfam (NCBI)pfam00130    pfam11971    pfam00169    pfam00621    pfam00017    pfam07653   
Domain families : Smart (EMBL)C1 (SM00109)  CH (SM00033)  PH (SM00233)  RhoGEF (SM00325)  SH2 (SM00252)  SH3 (SM00326)  
Conserved Domain (NCBI)VAV3
DMDM Disease mutations10451
Blocks (Seattle)VAV3
PDB (SRS)2D86   
PDB (PDBSum)2D86   
PDB (IMB)2D86   
PDB (RSDB)2D86   
Structural Biology KnowledgeBase2D86   
SCOP (Structural Classification of Proteins)2D86   
CATH (Classification of proteins structures)2D86   
SuperfamilyQ9UKW4
Human Protein AtlasENSG00000134215
Peptide AtlasQ9UKW4
HPRD05706
IPIIPI00299763   IPI00219689   IPI00976117   IPI00910879   IPI01009452   IPI00384729   IPI00981561   IPI00978808   IPI00980176   
Protein Interaction databases
DIP (DOE-UCLA)Q9UKW4
IntAct (EBI)Q9UKW4
FunCoupENSG00000134215
BioGRIDVAV3
STRING (EMBL)VAV3
ZODIACVAV3
Ontologies - Pathways
QuickGOQ9UKW4
Ontology : AmiGOangiogenesis  SH3/SH2 adaptor activity  guanyl-nucleotide exchange factor activity  guanyl-nucleotide exchange factor activity  Rho guanyl-nucleotide exchange factor activity  GTPase activator activity  epidermal growth factor receptor binding  protein binding  cytosol  plasma membrane  vesicle fusion  cellular response to DNA damage stimulus  integrin-mediated signaling pathway  small GTPase mediated signal transduction  regulation of cell size  regulation of cell size  positive regulation of signal transduction  lamellipodium assembly  platelet activation  neutrophil chemotaxis  Rac guanyl-nucleotide exchange factor activity  positive regulation of B cell proliferation  regulation of Rho protein signal transduction  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  response to drug  positive regulation of apoptotic process  regulation of GTPase activity  positive regulation of GTPase activity  positive regulation of GTPase activity  positive regulation of GTPase activity  positive regulation of phosphatidylinositol 3-kinase activity  positive regulation of cell adhesion  metal ion binding  vascular endothelial growth factor receptor signaling pathway  ephrin receptor signaling pathway  B cell receptor signaling pathway  regulation of small GTPase mediated signal transduction  extracellular exosome  
Ontology : EGO-EBIangiogenesis  SH3/SH2 adaptor activity  guanyl-nucleotide exchange factor activity  guanyl-nucleotide exchange factor activity  Rho guanyl-nucleotide exchange factor activity  GTPase activator activity  epidermal growth factor receptor binding  protein binding  cytosol  plasma membrane  vesicle fusion  cellular response to DNA damage stimulus  integrin-mediated signaling pathway  small GTPase mediated signal transduction  regulation of cell size  regulation of cell size  positive regulation of signal transduction  lamellipodium assembly  platelet activation  neutrophil chemotaxis  Rac guanyl-nucleotide exchange factor activity  positive regulation of B cell proliferation  regulation of Rho protein signal transduction  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  response to drug  positive regulation of apoptotic process  regulation of GTPase activity  positive regulation of GTPase activity  positive regulation of GTPase activity  positive regulation of GTPase activity  positive regulation of phosphatidylinositol 3-kinase activity  positive regulation of cell adhesion  metal ion binding  vascular endothelial growth factor receptor signaling pathway  ephrin receptor signaling pathway  B cell receptor signaling pathway  regulation of small GTPase mediated signal transduction  extracellular exosome  
Pathways : KEGGChemokine signaling pathway    Focal adhesion    Natural killer cell mediated cytotoxicity    T cell receptor signaling pathway    B cell receptor signaling pathway    Fc epsilon RI signaling pathway    Fc gamma R-mediated phagocytosis    Leukocyte transendothelial migration    Regulation of actin cytoskeleton   
REACTOMEQ9UKW4 [protein]
REACTOME Pathways114604 [pathway]   193648 [pathway]   194840 [pathway]   2029482 [pathway]   2424491 [pathway]   2871796 [pathway]   2871809 [pathway]   3928665 [pathway]   416482 [pathway]   4420097 [pathway]   5218920 [pathway]   
NDEx NetworkVAV3
Atlas of Cancer Signalling NetworkVAV3
Wikipedia pathwaysVAV3
Orthology - Evolution
OrthoDB10451
GeneTree (enSembl)ENSG00000134215
Phylogenetic Trees/Animal Genes : TreeFamVAV3
HOVERGENQ9UKW4
HOGENOMQ9UKW4
Homologs : HomoloGeneVAV3
Homology/Alignments : Family Browser (UCSC)VAV3
Gene fusions - Rearrangements
Fusion : MitelmanVAV3/DAB1 [1p13.3/1p32.2]  
Fusion : MitelmanVAV3/RGL1 [1p13.3/1q25.3]  [t(1;1)(p13;q25)]  
Fusion : MitelmanVAV3/ZHX2 [1p13.3/8q24.13]  [t(1;8)(p13;q24)]  
Fusion: TCGAVAV3 1p13.3 RGL1 1q25.3 BRCA
Fusion: TCGAVAV3 1p13.3 ZHX2 8q24.13 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerVAV3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)VAV3
dbVarVAV3
ClinVarVAV3
1000_GenomesVAV3 
Exome Variant ServerVAV3
ExAC (Exome Aggregation Consortium)VAV3 (select the gene name)
Genetic variants : HAPMAP10451
Genomic Variants (DGV)VAV3 [DGVbeta]
DECIPHER (Syndromes)1:108113782-108231126  ENSG00000134215
CONAN: Copy Number AnalysisVAV3 
Mutations
ICGC Data PortalVAV3 
TCGA Data PortalVAV3 
Broad Tumor PortalVAV3
OASIS PortalVAV3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICVAV3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDVAV3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch VAV3
DgiDB (Drug Gene Interaction Database)VAV3
DoCM (Curated mutations)VAV3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)VAV3 (select a term)
intoGenVAV3
NCG5 (London)VAV3
Cancer3DVAV3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM605541   
Orphanet
MedgenVAV3
Genetic Testing Registry VAV3
NextProtQ9UKW4 [Medical]
TSGene10451
GENETestsVAV3
Huge Navigator VAV3 [HugePedia]
snp3D : Map Gene to Disease10451
BioCentury BCIQVAV3
ClinGenVAV3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10451
Chemical/Pharm GKB GenePA37282
Clinical trialVAV3
Miscellaneous
canSAR (ICR)VAV3 (select the gene name)
Other databaseGeneNote
Other databaseH-InvDB
Other databaseECgene
Probes
Litterature
PubMed67 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineVAV3
EVEXVAV3
GoPubMedVAV3
iHOPVAV3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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