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Q9R0C8 (VAV3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Guanine nucleotide exchange factor VAV3

Short name=VAV-3
Gene names
Name:Vav3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length847 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7 Ref.8

Subunit structure

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. Ref.7

Tissue specificity

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

Post-translational modification

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

Disruption phenotype

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. Ref.6 Ref.8

Sequence similarities

Contains 1 CH (calponin-homology) domain.

Contains 1 DH (DBL-homology) domain.

Contains 1 PH domain.

Contains 1 phorbol-ester/DAG-type zinc finger.

Contains 1 SH2 domain.

Contains 2 SH3 domains.

Ontologies

Keywords
   Biological processAngiogenesis
   Coding sequence diversityAlternative promoter usage
Alternative splicing
   DomainRepeat
SH2 domain
SH3 domain
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionGuanine-nucleotide releasing factor
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

cell migration

Inferred from genetic interaction PubMed 15728722. Source: MGI

cell projection assembly

Inferred from genetic interaction PubMed 15728722. Source: MGI

cellular response to DNA damage stimulus

Inferred from electronic annotation. Source: Ensembl

integrin-mediated signaling pathway

Inferred from genetic interaction PubMed 15249579. Source: MGI

lamellipodium assembly

Inferred from genetic interaction PubMed 15728722. Source: MGI

neutrophil chemotaxis

Inferred from genetic interaction PubMed 21178006. Source: MGI

positive regulation of B cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell adhesion

Inferred from genetic interaction PubMed 15249579. Source: MGI

positive regulation of phosphatidylinositol 3-kinase activity

Inferred from genetic interaction PubMed 15728722. Source: MGI

regulation of GTPase activity

Inferred from genetic interaction PubMed 15249579. Source: MGI

regulation of Rac GTPase activity

Inferred from genetic interaction PubMed 15249579. Source: GOC

regulation of Rho GTPase activity

Inferred from genetic interaction PubMed 15249579. Source: GOC

response to drug

Inferred from electronic annotation. Source: Ensembl

small GTPase mediated signal transduction

Inferred from mutant phenotype PubMed 15728722. Source: MGI

vesicle fusion

Inferred from genetic interaction PubMed 15249579. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 15728722. Source: MGI

plasma membrane

Inferred from direct assay PubMed 15728722. Source: MGI

   Molecular_functionRac guanyl-nucleotide exchange factor activity

Inferred from genetic interaction PubMed 15249579. Source: MGI

Rho guanyl-nucleotide exchange factor activity

Inferred from genetic interaction PubMed 15249579. Source: MGI

epidermal growth factor receptor binding

Inferred from physical interaction PubMed 15728722. Source: MGI

guanyl-nucleotide exchange factor activity

Inferred from mutant phenotype PubMed 15728722. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.7. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9R0C8-1)

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.
Isoform 2 (identifier: Q9R0C8-2)

Also known as: Beta;

The sequence of this isoform is not available.
Isoform 3 (identifier: Q9R0C8-3)

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.
Isoform 4 (identifier: Q9R0C8-4)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 847847Guanine nucleotide exchange factor VAV3
PRO_0000080987

Regions

Domain1 – 119119CH
Domain192 – 371180DH
Domain400 – 502103PH
Domain592 – 66069SH3 1
Domain672 – 76695SH2
Domain788 – 84760SH3 2
Zinc finger513 – 56250Phorbol-ester/DAG-type
Region560 – 847288Sufficient for interaction with ROS1 By similarity

Amino acid modifications

Modified residue1411Phosphotyrosine By similarity

Natural variations

Alternative sequence1 – 560560Missing in isoform 3.
VSP_042360
Alternative sequence561 – 5688NCGRVNSV → MPIFTFVS in isoform 3.
VSP_042361
Alternative sequence569 – 5746EQGPFK → GKSCLL in isoform 4.
VSP_042362
Alternative sequence575 – 847273Missing in isoform 4.
VSP_042363

Experimental info

Sequence conflict3551K → R in BAC30879. Ref.2
Sequence conflict4521I → T in BAC28212. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified August 16, 2004. Version 2.
Checksum: 727C9BF50DF8CF19

FASTA84797,968
        10         20         30         40         50         60 
MEPWKQCAQW LIHSKVLPPN HRVTWDSAQV FDLAQTLRDG VLLCQLLNNL RPHSINLKEI 

        70         80         90        100        110        120 
NLRPQMSQFL CLKNIRTFLA ACCDTFGMRK SELFEAFDLF DVRDFGKVIE TLSRLSRTPI 

       130        140        150        160        170        180 
ALATGIRPFP TEESINDEDI YKGLPDLIDE TRVEDEEDLY DCVYGEDEGG EVYEDLMKAE 

       190        200        210        220        230        240 
EAQQPKSQEN DIRSCCLAEI RQTEEKYTET LESIEKYFMA PLKRFLTAAE FDSVFINIPD 

       250        260        270        280        290        300 
LVKVHRSLMQ EIHDSIVNKD DQNLYQVFIN YKERLVIYGQ YCSGVESAIS NLDYISKTKE 

       310        320        330        340        350        360 
DVKLKLEECS KRANNGKFTL RDLLVVPMQR VLKYHLLLQE LVKHTHDPME KANLKLALDA 

       370        380        390        400        410        420 
MKDLAQYVNE VKRDNETLRE IKQFQLSIEN LNQPVLLFGR PQGDGEIRIT TLDKHTKQER 

       430        440        450        460        470        480 
HIFLFDLAVI VCKRKGDNYE MKEIIDLQQY KIANNPTTDK ENKKWSYGFY LIHTQGQNGL 

       490        500        510        520        530        540 
EFYCKTKDLK KKWLEQFEMA LSNIRPDYAD SNFHDFKMHT FTRVTSCRVC QMLLRGTFYQ 

       550        560        570        580        590        600 
GYLCFKCGAK AHKECLGRVD NCGRVNSVEQ GPFKPPEKRT NGLRRASRQV DPGLPKMQVI 

       610        620        630        640        650        660 
RNYTGTPAPG LHEGPPLHIQ AGDTVELLRG DAHSVFWQGR NLASGEVGFF PSDAVKPSPC 

       670        680        690        700        710        720 
VPKPVDYSCQ PWYAGPMERL QAETELINRV NSTYLVRHRT KESGEYAISI KYNNEAKHIK 

       730        740        750        760        770        780 
ILTRDGFFHI AENRKFKSLM ELVEYYKHHS LKEGFRTLDT TLQFPYKEPE QPAGQRGNRT 

       790        800        810        820        830        840 
GNSLLSPKVL GIAIARYDFC ARDMRELSLL KGDMVKIYTK MSANGWWRGE VNGRVGWFPS 


TYVEEDE 

« Hide

Isoform 2 (Beta) (Sequence not available).
Isoform 3 (VAV3.1) [UniParc].

Checksum: BF2850B8F921F048
Show »

FASTA28732,662
Isoform 4 [UniParc].

Checksum: 6AB7C243493B6F2B
Show »

FASTA57466,849

References

« Hide 'large scale' references
[1]"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 245:139-149(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 1-789 (ISOFORM 3).
Tissue: Skin.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-731 (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Embryonic stomach and Embryonic testis.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain and Mammary tumor.
[5]Lubec G., Sunyer B., Chen W.-Q.
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 143-152, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: OF1.
Tissue: Hippocampus.
[6]"Vav3 regulates osteoclast function and bone mass."
Faccio R., Teitelbaum S.L., Fujikawa K., Chappel J., Zallone A., Tybulewicz V.L., Ross F.P., Swat W.
Nat. Med. 11:284-290(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]"Essential role of Vav family guanine nucleotide exchange factors in EphA receptor-mediated angiogenesis."
Hunter S.G., Zhuang G., Brantley-Sieders D.M., Swat W., Cowan C.W., Chen J.
Mol. Cell. Biol. 26:4830-4842(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EPHA2.
[8]"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 K.L., Walzog B., Bustelo X.R., Fischer K.D., Scharffetter-Kochanek K.
Blood 113:5266-5276(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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 expand/collapse EMBL AC list , CR936848, CR936849, CR938729 Genomic DNA. Translation: CAM28077.1.
CR938729, CR936848 Genomic DNA. Translation: CAM28109.1.
CR938729 expand/collapse EMBL AC list , CR936838, CR936848, CR936849 Genomic DNA. Translation: CAM28111.1.
CR936849 expand/collapse EMBL AC list , CR936838, CR936848, CR938729 Genomic DNA. Translation: CAM28160.1.
CR936848, CR938729 Genomic DNA. Translation: CAM28169.1.
CR936848 expand/collapse EMBL AC list , CR936838, CR936849, CR938729 Genomic DNA. Translation: CAM28172.1.
BC027242 mRNA. Translation: AAH27242.1.
BC052739 mRNA. Translation: AAH52739.1.
CCDSCCDS17773.1. [Q9R0C8-1]
CCDS59650.1. [Q9R0C8-3]
RefSeqNP_065251.2. NM_020505.2. [Q9R0C8-1]
NP_666251.1. NM_146139.2. [Q9R0C8-3]
UniGeneMm.282257.

3D structure databases

ProteinModelPortalQ9R0C8.
SMRQ9R0C8. Positions 1-563, 593-846.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000036270.

PTM databases

PhosphoSiteQ9R0C8.

Proteomic databases

PaxDbQ9R0C8.
PRIDEQ9R0C8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000046864; ENSMUSP00000036270; ENSMUSG00000033721. [Q9R0C8-1]
ENSMUST00000106576; ENSMUSP00000102186; ENSMUSG00000033721. [Q9R0C8-3]
GeneID57257.
KEGGmmu:57257.
UCSCuc008raf.1. mouse. [Q9R0C8-4]
uc008rag.1. mouse. [Q9R0C8-1]
uc008rah.1. mouse. [Q9R0C8-3]

Organism-specific databases

CTD10451.
MGIMGI:1888518. Vav3.

Phylogenomic databases

eggNOGNOG326494.
GeneTreeENSGT00740000115307.
HOGENOMHOG000234364.
HOVERGENHBG018066.
InParanoidQ9R0C8.
KOK05730.
OMADPGLPKM.
OrthoDBEOG73FQKZ.
PhylomeDBQ9R0C8.
TreeFamTF316171.

Gene expression databases

ArrayExpressQ9R0C8.
BgeeQ9R0C8.
CleanExMM_VAV3.
GenevestigatorQ9R0C8.

Family and domain databases

Gene3D1.10.418.10. 1 hit.
1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProIPR022613. CAMSAP_CH.
IPR001715. CH-domain.
IPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000980. SH2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
IPR003096. SM22_calponin.
IPR028530. Vav.
[Graphical view]
PANTHERPTHR22826:SF97. PTHR22826:SF97. 1 hit.
PfamPF00130. C1_1. 1 hit.
PF11971. CAMSAP_CH. 1 hit.
PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF00017. SH2. 1 hit.
PF07653. SH3_2. 2 hits.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00888. SM22CALPONIN.
SMARTSM00109. C1. 1 hit.
SM00033. CH. 1 hit.
SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]
SUPFAMSSF47576. SSF47576. 1 hit.
SSF48065. SSF48065. 1 hit.
SSF50044. SSF50044. 2 hits.
SSF55550. SSF55550. 2 hits.
PROSITEPS50021. 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.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSVAV3. mouse.
NextBio313559.
PROQ9R0C8.
SOURCESearch...

Entry information

Entry nameVAV3_MOUSE
AccessionPrimary (citable) accession number: Q9R0C8
Secondary accession number(s): A2CFD7 expand/collapse secondary AC list , Q7TS85, Q8BRV2, Q8CCF5, Q8R076, Q9JLS6
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: August 16, 2004
Last modified: July 9, 2014
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

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