UniProtKB - Q9R0C8 (VAV3_MOUSE)
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Protein
Guanine nucleotide exchange factor VAV3
Gene
Vav3
Organism
Mus musculus (Mouse)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Zinc fingeri | 513 – 562 | Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST | 50 |
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 function | Guanine-nucleotide releasing factor |
| Biological process | Angiogenesis |
| Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
| Reactomei | R-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 VAV3Short name: VAV-3 |
| Gene namesi | Name:Vav3 |
| Organismi | Mus musculus (Mouse) |
| Taxonomic identifieri | 10090 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
| Proteomesi |
|
Organism-specific databases
| MGIi | MGI:1888518. Vav3. |
Subcellular locationi
GO - Cellular componenti
- cytoplasm Source: MGI
- extracellular exosome Source: MGI
- plasma membrane Source: MGI
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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000080987 | 1 – 847 | Guanine nucleotide exchange factor VAV3Add BLAST | 847 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 141 | PhosphotyrosineBy similarity | 1 |
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
PhosphoproteinProteomic databases
| EPDi | Q9R0C8. |
| PaxDbi | Q9R0C8. |
| PeptideAtlasi | Q9R0C8. |
| PRIDEi | Q9R0C8. |
PTM databases
| iPTMneti | Q9R0C8. |
| PhosphoSitePlusi | Q9R0C8. |
Expressioni
Tissue specificityi
Abundantly expressed in osteoclasts and mature osteoblasts. Also expressed in bone marrow macrophages (at protein level):.
Gene expression databases
| Bgeei | ENSMUSG00000033721. |
| CleanExi | MM_VAV3. |
| Genevisiblei | Q9R0C8. 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
Protein-protein interaction databases
| BioGridi | 208227. 1 interactor. |
| STRINGi | 10090.ENSMUSP00000036270. |
Structurei
3D structure databases
| ProteinModelPortali | Q9R0C8. |
| SMRi | Q9R0C8. |
| ModBasei | Search... |
| MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 1 – 119 | Calponin-homologyPROSITE-ProRule annotationAdd BLAST | 119 | |
| Domaini | 192 – 371 | DHPROSITE-ProRule annotationAdd BLAST | 180 | |
| Domaini | 400 – 502 | PHPROSITE-ProRule annotationAdd BLAST | 103 | |
| Domaini | 592 – 660 | SH3 1PROSITE-ProRule annotationAdd BLAST | 69 | |
| Domaini | 672 – 766 | SH2PROSITE-ProRule annotationAdd BLAST | 95 | |
| Domaini | 788 – 847 | SH3 2PROSITE-ProRule annotationAdd BLAST | 60 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 560 – 847 | Sufficient for interaction with ROS1By similarityAdd BLAST | 288 |
Zinc finger
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Zinc fingeri | 513 – 562 | Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST | 50 |
Keywords - Domaini
Repeat, SH2 domain, SH3 domain, Zinc-fingerPhylogenomic databases
| eggNOGi | KOG2996. Eukaryota. ENOG410XPH6. LUCA. |
| GeneTreei | ENSGT00880000137925. |
| HOGENOMi | HOG000234364. |
| HOVERGENi | HBG018066. |
| InParanoidi | Q9R0C8. |
| KOi | K05730. |
| OMAi | GPPLHIQ. |
| OrthoDBi | EOG091G01O3. |
| PhylomeDBi | Q9R0C8. |
| TreeFami | TF316171. |
Family and domain databases
| CDDi | cd00029. C1. 1 hit. cd00014. CH. 1 hit. |
| Gene3Di | 1.10.418.10. 1 hit. 2.30.29.30. 1 hit. 3.30.505.10. 1 hit. |
| InterProi | View protein in InterPro IPR022613. CAMSAP_CH. IPR001715. CH-domain. IPR000219. DH-domain. IPR001331. GDS_CDC24_CS. IPR002219. PE/DAG-bd. IPR011993. PH_dom-like. IPR001849. PH_domain. IPR000980. SH2. IPR011511. SH3_2. IPR001452. SH3_domain. IPR003096. SM22_calponin. |
| Pfami | View 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. |
| PRINTSi | PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00888. SM22CALPONIN. |
| SMARTi | View 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. |
| SUPFAMi | SSF47576. SSF47576. 1 hit. SSF48065. SSF48065. 1 hit. SSF50044. SSF50044. 2 hits. SSF50729. SSF50729. 1 hit. SSF55550. SSF55550. 2 hits. |
| PROSITEi | View 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.
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
Isoform 2 (identifier: Q9R0C8-2)
Also known as: Beta
Sequence is not available
Length:–
Mass (Da):–
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 355 | K → R in BAC30879 (PubMed:16141072).Curated | 1 | |
| Sequence conflicti | 452 | I → T in BAC28212 (PubMed:16141072).Curated | 1 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_042360 | 1 – 560 | Missing in isoform 3. 2 PublicationsAdd BLAST | 560 | |
| Alternative sequenceiVSP_042361 | 561 – 568 | NCGRVNSV → MPIFTFVS in isoform 3. 2 Publications | 8 | |
| Alternative sequenceiVSP_042362 | 569 – 574 | EQGPFK → GKSCLL in isoform 4. 1 Publication | 6 | |
| Alternative sequenceiVSP_042363 | 575 – 847 | Missing in isoform 4. 1 PublicationAdd BLAST | 273 |
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 CR938729 Genomic DNA. Translation: CAM28077.1. CR938729, CR936848 Genomic DNA. Translation: CAM28109.1. CR938729 CR936849 Genomic DNA. Translation: CAM28111.1. CR936849 CR938729 Genomic DNA. Translation: CAM28160.1. CR936848, CR938729 Genomic DNA. Translation: CAM28169.1. CR936848 CR938729 Genomic DNA. Translation: CAM28172.1. BC027242 mRNA. Translation: AAH27242.1. BC052739 mRNA. Translation: AAH52739.1. |
| CCDSi | CCDS17773.1. [Q9R0C8-1] CCDS59650.1. [Q9R0C8-3] |
| RefSeqi | NP_065251.2. NM_020505.2. [Q9R0C8-1] NP_666251.1. NM_146139.2. [Q9R0C8-3] |
| UniGenei | Mm.282257. |
Genome annotation databases
| Ensembli | ENSMUST00000046864; ENSMUSP00000036270; ENSMUSG00000033721. [Q9R0C8-1] ENSMUST00000106576; ENSMUSP00000102186; ENSMUSG00000033721. [Q9R0C8-3] |
| GeneIDi | 57257. |
| KEGGi | mmu:57257. |
| UCSCi | uc008raf.1. mouse. [Q9R0C8-4] uc008rag.1. mouse. [Q9R0C8-1] uc008rah.1. mouse. [Q9R0C8-3] |
Keywords - Coding sequence diversityi
Alternative promoter usage, Alternative splicingSimilar proteinsi
Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:| 100% | UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry. |
| 90% | UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence). |
| 50% | UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster. |
Entry informationi
| Entry namei | VAV3_MOUSE | |
| Accessioni | Q9R0C8Primary (citable) accession number: Q9R0C8 Secondary accession number(s): A2CFD7 Q9JLS6 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 24, 2001 |
| Last sequence update: | August 16, 2004 | |
| Last modified: | July 5, 2017 | |
| This is version 157 of the entry and version 2 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
