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Protein

Guanine nucleotide exchange factor VAV3

Gene

Vav3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Exchange factor for GTP-binding proteins RhoA, RhoG and, to a lesser extent, Rac1. Binds physically to the nucleotide-free states of those GTPases (By similarity). Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. May be important for integrin-mediated signaling, at least in some cell types. In osteoclasts, along with SYK tyrosine kinase, required for signaling through integrin alpha-v/beta-1 (ITAGV-ITGB1), a crucial event for osteoclast proper cytoskeleton organization and function. This signaling pathway involves RAC1, but not RHO, activation. Necessary for proper wound healing. In the course of wound healing, required for the phagocytotic cup formation preceding macrophage phagocytosis of apoptotic neutrophils. Responsible for integrin beta-2-mediated macrophage adhesion and, to a lesser extent, contributes to beta-3-mediated adhesion. Does not affect integrin beta-1-mediated adhesion.By similarity3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri513 – 562Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST50

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: MGI
  • guanyl-nucleotide exchange factor activity Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • Rac guanyl-nucleotide exchange factor activity Source: MGI
  • Rho guanyl-nucleotide exchange factor activity Source: MGI

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • B cell receptor signaling pathway Source: MGI
  • cell migration Source: MGI
  • cell projection assembly Source: MGI
  • cellular response to DNA damage stimulus Source: MGI
  • integrin-mediated signaling pathway Source: MGI
  • lamellipodium assembly Source: MGI
  • neutrophil chemotaxis Source: MGI
  • positive regulation of B cell proliferation Source: MGI
  • positive regulation of cell adhesion Source: MGI
  • positive regulation of phosphatidylinositol 3-kinase activity Source: MGI
  • regulation of cell size Source: Ensembl
  • regulation of GTPase activity Source: MGI
  • regulation of Rho protein signal transduction Source: InterPro
  • response to drug Source: MGI
  • small GTPase mediated signal transduction Source: MGI
  • vesicle fusion Source: MGI

Keywordsi

Molecular functionGuanine-nucleotide releasing factor
Biological processAngiogenesis
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-114604 GPVI-mediated activation cascade
R-MMU-193648 NRAGE signals death through JNK
R-MMU-194840 Rho GTPase cycle
R-MMU-2029482 Regulation of actin dynamics for phagocytic cup formation
R-MMU-2424491 DAP12 signaling
R-MMU-2871796 FCERI mediated MAPK activation
R-MMU-2871809 FCERI mediated Ca+2 mobilization
R-MMU-3928665 EPH-ephrin mediated repulsion of cells
R-MMU-416482 G alpha (12/13) signalling events
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-5218920 VEGFR2 mediated vascular permeability

Names & Taxonomyi

Protein namesi
Recommended name:
Guanine nucleotide exchange factor VAV3
Short name:
VAV-3
Gene namesi
Name:Vav3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1888518 Vav3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Disruption phenotypei

Mutant mice exhibit increased bone density, due to diminished bone resorption, including following parathyroid hormone treatment. This phenotype is due to defective terminal osteoclast differentiation. They also show a delayed wound repair program, characterized by a deficit in macrophage emigration to the wound, a reduced myofibroblast-dependent wound contraction and a diminished neovascularization in the restoration tissue.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809871 – 847Guanine nucleotide exchange factor VAV3Add BLAST847

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei141PhosphotyrosineBy similarity1

Post-translational modificationi

Phosphorylated. Phosphorylation can be mediated by ROS1 (By similarity). In osteoclasts, undergoes tyrosine phosphorylation in response to CSF1.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9R0C8
PaxDbiQ9R0C8
PeptideAtlasiQ9R0C8
PRIDEiQ9R0C8

PTM databases

iPTMnetiQ9R0C8
PhosphoSitePlusiQ9R0C8

Expressioni

Tissue specificityi

Abundantly expressed in osteoclasts and mature osteoblasts. Also expressed in bone marrow macrophages (at protein level):.

Gene expression databases

BgeeiENSMUSG00000033721
CleanExiMM_VAV3
GenevisibleiQ9R0C8 MM

Interactioni

Subunit structurei

Interacts with the PH domain of APS. Interacts with ROS1; constitutive interaction that mediates VAV3 phosphorylation (By similarity). Interacts (via SH2 domains) with the phosphorylated form of EPHA2.By similarity1 Publication

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: MGI
  • guanyl-nucleotide exchange factor activity Source: MGI
  • Rac guanyl-nucleotide exchange factor activity Source: MGI
  • Rho guanyl-nucleotide exchange factor activity Source: MGI

Protein-protein interaction databases

BioGridi208227, 1 interactor
STRINGi10090.ENSMUSP00000036270

Structurei

3D structure databases

ProteinModelPortaliQ9R0C8
SMRiQ9R0C8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 119Calponin-homology (CH)PROSITE-ProRule annotationAdd BLAST119
Domaini192 – 371DHPROSITE-ProRule annotationAdd BLAST180
Domaini400 – 502PHPROSITE-ProRule annotationAdd BLAST103
Domaini592 – 660SH3 1PROSITE-ProRule annotationAdd BLAST69
Domaini672 – 766SH2PROSITE-ProRule annotationAdd BLAST95
Domaini788 – 847SH3 2PROSITE-ProRule annotationAdd BLAST60

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni560 – 847Sufficient for interaction with ROS1By similarityAdd BLAST288

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri513 – 562Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST50

Keywords - Domaini

Repeat, SH2 domain, SH3 domain, Zinc-finger

Phylogenomic databases

eggNOGiKOG2996 Eukaryota
ENOG410XPH6 LUCA
GeneTreeiENSGT00910000144110
HOGENOMiHOG000234364
HOVERGENiHBG018066
InParanoidiQ9R0C8
KOiK05730
OMAiLGRVDNC
OrthoDBiEOG091G01O3
PhylomeDBiQ9R0C8
TreeFamiTF316171

Family and domain databases

CDDicd00029 C1, 1 hit
cd00014 CH, 1 hit
cd01223 PH_Vav, 1 hit
cd00160 RhoGEF, 1 hit
cd10407 SH2_Vav3, 1 hit
cd11978 SH3_VAV3_2, 1 hit
Gene3Di1.10.418.10, 1 hit
1.20.900.10, 1 hit
2.30.29.30, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR022613 CAMSAP_CH
IPR001715 CH-domain
IPR036872 CH_dom_sf
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR001331 GDS_CDC24_CS
IPR002219 PE/DAG-bd
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR037832 PH_Vav
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR003096 SM22_calponin
IPR035881 VAV3_SH2
IPR035734 VAV3_SH3_2
PfamiView protein in Pfam
PF00130 C1_1, 1 hit
PF11971 CAMSAP_CH, 1 hit
PF00169 PH, 1 hit
PF00621 RhoGEF, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PF07653 SH3_2, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00888 SM22CALPONIN
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00033 CH, 1 hit
SM00233 PH, 1 hit
SM00325 RhoGEF, 1 hit
SM00252 SH2, 1 hit
SM00326 SH3, 2 hits
SUPFAMiSSF47576 SSF47576, 1 hit
SSF48065 SSF48065, 1 hit
SSF50044 SSF50044, 2 hits
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50021 CH, 1 hit
PS00741 DH_1, 1 hit
PS50010 DH_2, 1 hit
PS50003 PH_DOMAIN, 1 hit
PS50001 SH2, 1 hit
PS50002 SH3, 2 hits
PS00479 ZF_DAG_PE_1, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9R0C8-1) [UniParc]FASTAAdd to basket
Also known as: Alpha

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEPWKQCAQW LIHSKVLPPN HRVTWDSAQV FDLAQTLRDG VLLCQLLNNL
60 70 80 90 100
RPHSINLKEI NLRPQMSQFL CLKNIRTFLA ACCDTFGMRK SELFEAFDLF
110 120 130 140 150
DVRDFGKVIE TLSRLSRTPI ALATGIRPFP TEESINDEDI YKGLPDLIDE
160 170 180 190 200
TRVEDEEDLY DCVYGEDEGG EVYEDLMKAE EAQQPKSQEN DIRSCCLAEI
210 220 230 240 250
RQTEEKYTET LESIEKYFMA PLKRFLTAAE FDSVFINIPD LVKVHRSLMQ
260 270 280 290 300
EIHDSIVNKD DQNLYQVFIN YKERLVIYGQ YCSGVESAIS NLDYISKTKE
310 320 330 340 350
DVKLKLEECS KRANNGKFTL RDLLVVPMQR VLKYHLLLQE LVKHTHDPME
360 370 380 390 400
KANLKLALDA MKDLAQYVNE VKRDNETLRE IKQFQLSIEN LNQPVLLFGR
410 420 430 440 450
PQGDGEIRIT TLDKHTKQER HIFLFDLAVI VCKRKGDNYE MKEIIDLQQY
460 470 480 490 500
KIANNPTTDK ENKKWSYGFY LIHTQGQNGL EFYCKTKDLK KKWLEQFEMA
510 520 530 540 550
LSNIRPDYAD SNFHDFKMHT FTRVTSCRVC QMLLRGTFYQ GYLCFKCGAK
560 570 580 590 600
AHKECLGRVD NCGRVNSVEQ GPFKPPEKRT NGLRRASRQV DPGLPKMQVI
610 620 630 640 650
RNYTGTPAPG LHEGPPLHIQ AGDTVELLRG DAHSVFWQGR NLASGEVGFF
660 670 680 690 700
PSDAVKPSPC VPKPVDYSCQ PWYAGPMERL QAETELINRV NSTYLVRHRT
710 720 730 740 750
KESGEYAISI KYNNEAKHIK ILTRDGFFHI AENRKFKSLM ELVEYYKHHS
760 770 780 790 800
LKEGFRTLDT TLQFPYKEPE QPAGQRGNRT GNSLLSPKVL GIAIARYDFC
810 820 830 840
ARDMRELSLL KGDMVKIYTK MSANGWWRGE VNGRVGWFPS TYVEEDE
Length:847
Mass (Da):97,968
Last modified:August 16, 2004 - v2
Checksum:i727C9BF50DF8CF19
GO
Isoform 2 (identifier: Q9R0C8-2)
Also known as: Beta
Sequence is not available
Length:
Mass (Da):
Isoform 3 (identifier: Q9R0C8-3) [UniParc]FASTAAdd to basket
Also known as: VAV3.1

The sequence of this isoform differs from the canonical sequence as follows:
     1-560: Missing.
     561-568: NCGRVNSV → MPIFTFVS

Note: Produced by alternative promoter usage.
Show »
Length:287
Mass (Da):32,662
Checksum:iBF2850B8F921F048
GO
Isoform 4 (identifier: Q9R0C8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     569-574: EQGPFK → GKSCLL
     575-847: Missing.

Note: Produced by alternative splicing. No experimental confirmation available.
Show »
Length:574
Mass (Da):66,849
Checksum:i6AB7C243493B6F2B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti355K → R in BAC30879 (PubMed:16141072).Curated1
Sequence conflicti452I → T in BAC28212 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0423601 – 560Missing in isoform 3. 2 PublicationsAdd BLAST560
Alternative sequenceiVSP_042361561 – 568NCGRVNSV → MPIFTFVS in isoform 3. 2 Publications8
Alternative sequenceiVSP_042362569 – 574EQGPFK → GKSCLL in isoform 4. 1 Publication6
Alternative sequenceiVSP_042363575 – 847Missing in isoform 4. 1 PublicationAdd BLAST273

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF067816 mRNA Translation: AAF09171.1
AF140280 mRNA Translation: AAF20330.2
AK033253 mRNA Translation: BAC28212.1
AK041249 mRNA Translation: BAC30879.2
AK147053 mRNA Translation: BAE27637.1
AL731716, AL671857, AL671987 Genomic DNA Translation: CAM14541.1
AL671857, AL671987, AL731716 Genomic DNA Translation: CAM16459.1
AL671987, AL731716, AL671857 Genomic DNA Translation: CAM18527.1
CR936838
, CR936848, CR936849, CR938729 Genomic DNA Translation: CAM28077.1
CR938729, CR936848 Genomic DNA Translation: CAM28109.1
CR938729
, CR936838, CR936848, CR936849 Genomic DNA Translation: CAM28111.1
CR936849
, CR936838, CR936848, CR938729 Genomic DNA Translation: CAM28160.1
CR936848, CR938729 Genomic DNA Translation: CAM28169.1
CR936848
, CR936838, CR936849, CR938729 Genomic DNA Translation: CAM28172.1
BC027242 mRNA Translation: AAH27242.1
BC052739 mRNA Translation: AAH52739.1
CCDSiCCDS17773.1 [Q9R0C8-1]
CCDS59650.1 [Q9R0C8-3]
RefSeqiNP_065251.2, NM_020505.2 [Q9R0C8-1]
NP_666251.1, NM_146139.2 [Q9R0C8-3]
UniGeneiMm.282257

Genome annotation databases

EnsembliENSMUST00000046864; ENSMUSP00000036270; ENSMUSG00000033721 [Q9R0C8-1]
ENSMUST00000106576; ENSMUSP00000102186; ENSMUSG00000033721 [Q9R0C8-3]
GeneIDi57257
KEGGimmu:57257
UCSCiuc008raf.1 mouse [Q9R0C8-4]
uc008rag.1 mouse [Q9R0C8-1]
uc008rah.1 mouse [Q9R0C8-3]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiVAV3_MOUSE
AccessioniPrimary (citable) accession number: Q9R0C8
Secondary accession number(s): A2CFD7
, Q7TS85, Q8BRV2, Q8CCF5, Q8R076, Q9JLS6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: August 16, 2004
Last modified: March 28, 2018
This is version 162 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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