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Protein

Proto-oncogene vav

Gene

VAV1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.

Miscellaneous

'Vav' stands for the sixth letter of the Hebrew alphabet.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri515 – 564Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST50

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGuanine-nucleotide releasing factor
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-114604 GPVI-mediated activation cascade
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-193648 NRAGE signals death through JNK
R-HSA-194840 Rho GTPase cycle
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-389359 CD28 dependent Vav1 pathway
R-HSA-416482 G alpha (12/13) signalling events
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-5218920 VEGFR2 mediated vascular permeability
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-912631 Regulation of signaling by CBL
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
SignaLinkiP15498
SIGNORiP15498

Names & Taxonomyi

Protein namesi
Recommended name:
Proto-oncogene vav
Gene namesi
Name:VAV1
Synonyms:VAV
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000141968.7
HGNCiHGNC:12657 VAV1
MIMi164875 gene
neXtProtiNX_P15498

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi529C → R: Abolishes transforming activity. 1 Publication1
Mutagenesisi696R → L: Loss of interaction with SYK. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi7409
OpenTargetsiENSG00000141968
PharmGKBiPA37280

Chemistry databases

ChEMBLiCHEMBL3259472

Polymorphism and mutation databases

BioMutaiVAV1
DMDMi13124807

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809801 – 845Proto-oncogene vavAdd BLAST845

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei826PhosphotyrosineCombined sources1
Modified residuei844PhosphotyrosineBy similarity1

Post-translational modificationi

Phosphorylated on tyrosine residues by HCK in response to IFNG and bacterial lipopolysaccharide (LPS) (By similarity). Phosphorylated by FYN.By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP15498
MaxQBiP15498
PaxDbiP15498
PeptideAtlasiP15498
PRIDEiP15498
ProteomicsDBi53143

PTM databases

iPTMnetiP15498
PhosphoSitePlusiP15498

Miscellaneous databases

PMAP-CutDBiP15498

Expressioni

Tissue specificityi

Widely expressed in hematopoietic cells but not in other cell types.

Gene expression databases

BgeeiENSG00000141968
CleanExiHS_VAV1
ExpressionAtlasiP15498 baseline and differential
GenevisibleiP15498 HS

Organism-specific databases

HPAiHPA001864

Interactioni

Subunit structurei

Interacts with SHB (PubMed:12084069). Interacts with APS, GRB2, GRB3, DOCK2, SLA, TEC and ZNF655/VIK (PubMed:12393632, PubMed:12400014, PubMed:15558030). Interacts with SIAH2; without leading to its degradation (PubMed:10207103). Associates with BLNK, PLCG1, GRB2 and NCK1 in a B-cell antigen receptor-dependent fashion (PubMed:9697839). Interacts with CBLB; which inhibits tyrosine phosphorylation and down-regulates activity (PubMed:9399639). May interact with CCPG1. Interacts with CLNK. Interacts with THEMIS2 (By similarity). Interacts with NEK3 and this interaction is prolactin-dependent (PubMed:15618286). Interacts with ITK (PubMed:15661896). Interacts with PTK2B/PYK2 (By similarity). Interacts with HCK. Interacts with PTK2B/PYK2 (PubMed:19207108). Interacts (via SH2 domain) with SYK (PubMed:8986718). Interacts with ANKRD54. Interacts with CD6 (By similarity).By similarity11 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113252, 88 interactors
CORUMiP15498
DIPiDIP-1061N
IntActiP15498, 29 interactors
MINTiP15498
STRINGi9606.ENSP00000472929

Chemistry databases

BindingDBiP15498

Structurei

Secondary structure

1845
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 13Combined sources11
Turni22 – 24Combined sources3
Helixi30 – 37Combined sources8
Helixi41 – 50Combined sources10
Helixi57 – 59Combined sources3
Helixi68 – 84Combined sources17
Helixi96 – 100Combined sources5
Helixi105 – 117Combined sources13
Turni119 – 121Combined sources3
Helixi122 – 124Combined sources3
Helixi145 – 149Combined sources5
Helixi159 – 162Combined sources4
Helixi168 – 178Combined sources11
Helixi191 – 218Combined sources28
Helixi221 – 224Combined sources4
Turni225 – 227Combined sources3
Helixi230 – 237Combined sources8
Helixi240 – 259Combined sources20
Turni260 – 262Combined sources3
Helixi267 – 273Combined sources7
Helixi276 – 278Combined sources3
Helixi279 – 300Combined sources22
Helixi302 – 316Combined sources15
Beta strandi317 – 319Combined sources3
Helixi322 – 326Combined sources5
Helixi328 – 333Combined sources6
Helixi336 – 344Combined sources9
Helixi351 – 388Combined sources38
Helixi397 – 400Combined sources4
Beta strandi403 – 412Combined sources10
Beta strandi420 – 435Combined sources16
Beta strandi442 – 448Combined sources7
Helixi449 – 451Combined sources3
Beta strandi452 – 456Combined sources5
Beta strandi469 – 479Combined sources11
Beta strandi481 – 488Combined sources8
Helixi489 – 506Combined sources18
Turni509 – 512Combined sources4
Helixi513 – 515Combined sources3
Beta strandi518 – 521Combined sources4
Turni530 – 532Combined sources3
Beta strandi538 – 540Combined sources3
Beta strandi543 – 546Combined sources4
Turni547 – 549Combined sources3
Helixi555 – 560Combined sources6
Helixi666 – 668Combined sources3
Beta strandi669 – 672Combined sources4
Helixi678 – 684Combined sources7
Turni685 – 687Combined sources3
Beta strandi692 – 696Combined sources5
Beta strandi700 – 702Combined sources3
Beta strandi706 – 711Combined sources6
Beta strandi714 – 719Combined sources6
Beta strandi721 – 723Combined sources3
Beta strandi726 – 730Combined sources5
Beta strandi735 – 737Combined sources3
Helixi738 – 745Combined sources8
Helixi750 – 752Combined sources3
Beta strandi754 – 756Combined sources3
Beta strandi763 – 766Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CRHNMR-A629-775[»]
2LCTNMR-A664-767[»]
2MC1NMR-A664-767[»]
2RORNMR-A629-775[»]
3BJIX-ray2.60A/B189-565[»]
3KY9X-ray2.73A/B2-584[»]
ProteinModelPortaliP15498
SMRiP15498
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15498

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 119Calponin-homology (CH)PROSITE-ProRule annotationAdd BLAST119
Domaini194 – 373DHPROSITE-ProRule annotationAdd BLAST180
Domaini402 – 504PHPROSITE-ProRule annotationAdd BLAST103
Domaini592 – 660SH3 1PROSITE-ProRule annotationAdd BLAST69
Domaini671 – 765SH2PROSITE-ProRule annotationAdd BLAST95
Domaini782 – 842SH3 2PROSITE-ProRule annotationAdd BLAST61

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi33 – 99Leu-richAdd BLAST67

Domaini

The DH domain is involved in interaction with CCPG1.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri515 – 564Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST50

Keywords - Domaini

Repeat, SH2 domain, SH3 domain, Zinc-finger

Phylogenomic databases

eggNOGiKOG2996 Eukaryota
ENOG410XPH6 LUCA
GeneTreeiENSGT00920000148946
HOGENOMiHOG000234364
HOVERGENiHBG018066
InParanoidiP15498
KOiK05730
OMAiDKRECCL
OrthoDBiEOG091G01O3
PhylomeDBiP15498
TreeFamiTF316171

Family and domain databases

CDDicd00029 C1, 1 hit
cd01223 PH_Vav, 1 hit
cd00160 RhoGEF, 1 hit
cd10405 SH2_Vav1, 1 hit
cd11979 SH3_VAV1_1, 1 hit
cd11976 SH3_VAV1_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
IPR028530 Vav1
IPR035879 VAV1_SH2
IPR035730 VAV1_SH3_1
IPR035729 VAV1_SH3_2
PANTHERiPTHR22826:SF112 PTHR22826:SF112, 1 hit
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, 2 hits
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, 1 hit
SSF55550 SSF55550, 1 hit
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P15498-1) [UniParc]FASTAAdd to basket

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
MELWRQCTHW LIQCRVLPPS HRVTWDGAQV CELAQALRDG VLLCQLLNNL
60 70 80 90 100
LPHAINLREV NLRPQMSQFL CLKNIRTFLS TCCEKFGLKR SELFEAFDLF
110 120 130 140 150
DVQDFGKVIY TLSALSWTPI AQNRGIMPFP TEEESVGDED IYSGLSDQID
160 170 180 190 200
DTVEEDEDLY DCVENEEAEG DEIYEDLMRS EPVSMPPKMT EYDKRCCCLR
210 220 230 240 250
EIQQTEEKYT DTLGSIQQHF LKPLQRFLKP QDIEIIFINI EDLLRVHTHF
260 270 280 290 300
LKEMKEALGT PGAANLYQVF IKYKERFLVY GRYCSQVESA SKHLDRVAAA
310 320 330 340 350
REDVQMKLEE CSQRANNGRF TLRDLLMVPM QRVLKYHLLL QELVKHTQEA
360 370 380 390 400
MEKENLRLAL DAMRDLAQCV NEVKRDNETL RQITNFQLSI ENLDQSLAHY
410 420 430 440 450
GRPKIDGELK ITSVERRSKM DRYAFLLDKA LLICKRRGDS YDLKDFVNLH
460 470 480 490 500
SFQVRDDSSG DRDNKKWSHM FLLIEDQGAQ GYELFFKTRE LKKKWMEQFE
510 520 530 540 550
MAISNIYPEN ATANGHDFQM FSFEETTSCK ACQMLLRGTF YQGYRCHRCR
560 570 580 590 600
ASAHKECLGR VPPCGRHGQD FPGTMKKDKL HRRAQDKKRN ELGLPKMEVF
610 620 630 640 650
QEYYGLPPPP GAIGPFLRLN PGDIVELTKA EAEQNWWEGR NTSTNEIGWF
660 670 680 690 700
PCNRVKPYVH GPPQDLSVHL WYAGPMERAG AESILANRSD GTFLVRQRVK
710 720 730 740 750
DAAEFAISIK YNVEVKHIKI MTAEGLYRIT EKKAFRGLTE LVEFYQQNSL
760 770 780 790 800
KDCFKSLDTT LQFPFKEPEK RTISRPAVGS TKYFGTAKAR YDFCARDRSE
810 820 830 840
LSLKEGDIIK ILNKKGQQGW WRGEIYGRVG WFPANYVEED YSEYC
Length:845
Mass (Da):98,314
Last modified:February 21, 2001 - v4
Checksum:iAC3BC9736FD2F138
GO
Isoform 2 (identifier: P15498-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     187-218: Missing.

Note: No experimental confirmation available.
Show »
Length:813
Mass (Da):94,493
Checksum:i2DD711DA5E0A8403
GO

Sequence cautioni

The sequence BAG62721 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA34383 differs from that shown. Reason: Frameshift at positions 322 and 355.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti264A → P in CAA34383 (PubMed:2477241).Curated1
Sequence conflicti368Q → R in BAG62721 (PubMed:14702039).Curated1
Sequence conflicti718I → TV (PubMed:2477241).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051997739T → M. Corresponds to variant dbSNP:rs36097961Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047563187 – 218Missing in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030227
, AF030201, AF030202, AF030203, AF030204, AF030205, AF030206, AF030207, AF030208, AF030209, AF030210, AF030211, AF030212, AF030213, AF030214, AF030215, AF030216, AF030217, AF030218, AF030219, AF030220, AF030221, AF030222, AF030223, AF030224, AF030225, AF030226 Genomic DNA Translation: AAC25011.1
AC010647 Genomic DNA No translation available.
AC020895 Genomic DNA No translation available.
AC020954 Genomic DNA No translation available.
AC022156 Genomic DNA No translation available.
M59834 Genomic DNA Translation: AAA63267.1
AK301128 mRNA Translation: BAG62721.1 Different initiation.
X16316 mRNA Translation: CAA34383.1 Frameshift.
X83931 mRNA Translation: CAA58783.1
CCDSiCCDS12174.1 [P15498-1]
CCDS59342.1 [P15498-2]
PIRiB39576 TVHUVV
RefSeqiNP_001245136.1, NM_001258207.1 [P15498-2]
NP_005419.2, NM_005428.3 [P15498-1]
UniGeneiHs.116237

Genome annotation databases

EnsembliENST00000596764; ENSP00000469450; ENSG00000141968 [P15498-2]
ENST00000602142; ENSP00000472929; ENSG00000141968 [P15498-1]
GeneIDi7409
KEGGihsa:7409
UCSCiuc002mfu.3 human [P15498-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiVAV_HUMAN
AccessioniPrimary (citable) accession number: P15498
Secondary accession number(s): B4DVK9, M0QXX6, Q15860
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: February 21, 2001
Last modified: June 20, 2018
This is version 215 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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