P15498 (VAV_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proto-oncogene vav

Gene names

Name:	VAV1
Synonyms:	VAV

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	845 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.
Subunit structure	May interact with CCPG1 By similarity. Interacts with APS, DOCK2, GRB2, GRB3, DOCK2, SLA, TEC and ZNF655/VIK. Interacts with SIAH2; without leading to its degradation. Associates with BLNK, PLCG1, GRB2 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with CBLB; which inhibits tyrosine phosphorylation and down-regulates activity. Interacts with SHB and CLNK By similarity. Interacts with THEMIS2. Interacts with HCK By similarity. Interacts with NEK3 and this interaction is prolactin-dependent. Interacts with ITK. Interacts with PTK2B/PYK2. Interacts (via SH2 domain) with SYK. Interacts with ANKRD54 By similarity. Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20
Tissue specificity	Widely expressed in hematopoietic cells but not in other cell types.
Domain	The DH domain is involved in interaction with CCPG1 By similarity.
Post-translational modification	Phosphorylated on tyrosine residues by HCK in response to IFNG and bacterial lipopolysaccharide (LPS) By similarity. Phosphorylated by FYN. Ref.12
Miscellaneous	'Vav' stands for the sixth letter of the Hebrew alphabet.
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.
Sequence caution	The sequence CAA34383.1 differs from that shown. Reason: Frameshift at positions 322 and 355.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Disease	Proto-oncogene
Domain	Repeat SH2 domain SH3 domain Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome
Molecular_function	Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro guanyl-nucleotide exchange factor activity Traceable author statement. Source: Reactome metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phospholipid binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Traceable author statement Ref.4. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	2	EBI-625518,EBI-401755
ZNF655	Q8N720	5	EBI-625518,EBI-625509

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 845

845

Proto-oncogene vav

PRO_0000080980

Regions

Domain

1 – 119

119

CH

Domain

194 – 373

180

DH

Domain

402 – 504

103

PH

Domain

617 – 660

44

SH3 1

Domain

671 – 765

95

SH2

Domain

782 – 842

61

SH3 2

Zinc finger

515 – 564

50

Phorbol-ester/DAG-type

Compositional bias

33 – 99

67

Leu-rich

Amino acid modifications

Modified residue

826

1

Phosphotyrosine Ref.18

Modified residue

844

1

Phosphotyrosine By similarity

Natural variations

Natural variant

739

1

T → M.
Corresponds to variant rs36097961 [ dbSNP | Ensembl ].

VAR_051997

Experimental info

Mutagenesis

529

1

C → R: Abolishes transforming activity. Ref.1

Mutagenesis

696

1

R → L: Loss of interaction with SYK. Ref.8

Sequence conflict

264

1

A → P in CAA34383. Ref.4

Sequence conflict

718

1

I → TV Ref.4

Secondary structure

1

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845

Helix Strand Turn

Details...

Helix

3 – 13

11

Turn

22 – 24

3

Helix

30 – 37

8

Helix

41 – 50

10

Helix

57 – 59

3

Helix

68 – 84

17

Helix

96 – 100

5

Helix

105 – 117

13

Turn

119 – 121

3

Helix

122 – 124

3

Helix

145 – 149

5

Helix

159 – 162

4

Helix

168 – 178

11

Helix

191 – 218

28

Helix

221 – 224

4

Turn

225 – 227

3

Helix

230 – 237

8

Helix

240 – 259

20

Turn

260 – 262

3

Helix

267 – 273

7

Helix

276 – 278

3

Helix

279 – 300

22

Helix

302 – 316

15

Beta strand

317 – 319

3

Helix

322 – 326

5

Helix

328 – 333

6

Helix

336 – 344

9

Helix

351 – 388

38

Helix

397 – 400

4

Beta strand

403 – 412

10

Beta strand

420 – 435

16

Beta strand

442 – 448

7

Helix

449 – 451

3

Beta strand

452 – 456

5

Beta strand

469 – 479

11

Beta strand

481 – 488

8

Helix

489 – 506

18

Turn

509 – 512

4

Helix

513 – 515

3

Beta strand

518 – 521

4

Turn

530 – 532

3

Beta strand

538 – 540

3

Beta strand

543 – 546

4

Turn

547 – 549

3

Helix

555 – 560

6

Helix

666 – 668

3

Beta strand

669 – 672

4

Helix

678 – 684

7

Turn

685 – 687

3

Beta strand

692 – 696

5

Beta strand

700 – 702

3

Beta strand

706 – 711

6

Beta strand

714 – 719

6

Beta strand

721 – 723

3

Beta strand

726 – 730

5

Beta strand

735 – 737

3

Helix

738 – 745

8

Helix

750 – 752

3

Beta strand

754 – 756

3

Beta strand

763 – 766

4

Sequences

	Sequence		Length	Mass (Da)
	P15498 [UniParc]. Last modified February 21, 2001. Version 4. Checksum: AC3BC9736FD2F138	FASTA	845	98,314
	10 20 30 40 50 60 MELWRQCTHW LIQCRVLPPS HRVTWDGAQV CELAQALRDG VLLCQLLNNL LPHAINLREV 70 80 90 100 110 120 NLRPQMSQFL CLKNIRTFLS TCCEKFGLKR SELFEAFDLF DVQDFGKVIY TLSALSWTPI 130 140 150 160 170 180 AQNRGIMPFP TEEESVGDED IYSGLSDQID DTVEEDEDLY DCVENEEAEG DEIYEDLMRS 190 200 210 220 230 240 EPVSMPPKMT EYDKRCCCLR EIQQTEEKYT DTLGSIQQHF LKPLQRFLKP QDIEIIFINI 250 260 270 280 290 300 EDLLRVHTHF LKEMKEALGT PGAANLYQVF IKYKERFLVY GRYCSQVESA SKHLDRVAAA 310 320 330 340 350 360 REDVQMKLEE CSQRANNGRF TLRDLLMVPM QRVLKYHLLL QELVKHTQEA MEKENLRLAL 370 380 390 400 410 420 DAMRDLAQCV NEVKRDNETL RQITNFQLSI ENLDQSLAHY GRPKIDGELK ITSVERRSKM 430 440 450 460 470 480 DRYAFLLDKA LLICKRRGDS YDLKDFVNLH SFQVRDDSSG DRDNKKWSHM FLLIEDQGAQ 490 500 510 520 530 540 GYELFFKTRE LKKKWMEQFE MAISNIYPEN ATANGHDFQM FSFEETTSCK ACQMLLRGTF 550 560 570 580 590 600 YQGYRCHRCR ASAHKECLGR VPPCGRHGQD FPGTMKKDKL HRRAQDKKRN ELGLPKMEVF 610 620 630 640 650 660 QEYYGLPPPP GAIGPFLRLN PGDIVELTKA EAEQNWWEGR NTSTNEIGWF PCNRVKPYVH 670 680 690 700 710 720 GPPQDLSVHL WYAGPMERAG AESILANRSD GTFLVRQRVK DAAEFAISIK YNVEVKHIKI 730 740 750 760 770 780 MTAEGLYRIT EKKAFRGLTE LVEFYQQNSL KDCFKSLDTT LQFPFKEPEK RTISRPAVGS 790 800 810 820 830 840 TKYFGTAKAR YDFCARDRSE LSLKEGDIIK ILNKKGQQGW WRGEIYGRVG WFPANYVEED YSEYC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mechanism of activation of the vav protooncogene." Coppola J., Bryant S., Koda T., Conway D., Barbacid M. Cell Growth Differ. 2:95-105(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF CYS-529.
[2]	"Genomic organization and regulation of the vav proto-oncogene." Denkinger D.J., Borges C.R., Butler C.L., Cushman A.M., Kawahara R.S. Biochim. Biophys. Acta 1491:253-262(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Loss of the amino-terminal helix-loop-helix domain of the vav proto-oncogene activates its transforming potential." Katzav S., Cleveland J.L., Heslop H.E., Pulido D. Mol. Cell. Biol. 11:1912-1920(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-61.
[4]	"vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells." Katzav S., Martin-Zanca D., Barbacid M. EMBO J. 8:2283-2290(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 68-845.
[5]	Romero F. Submitted (JAN-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 299-837.
[6]	"The proline-rich region of Vav binds to Grb2 and Grb3-3." Ramos-Morales F., Romero F., Schweighoffer F., Bismuth G., Camonis J., Tortolero M., Fischer S. Oncogene 11:1665-1669(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 299-334.
[7]	"The hematopoietically expressed vav proto-oncogene shares homology with the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization." Adams J.M., Houston H., Allen J., Lints T., Harvey R. Oncogene 7:611-618(1992) [PubMed] [Europe PMC] [Abstract] Cited for: SIMILARITY TO CDC24 FAMILY.
[8]	"Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product." Deckert M., Tartare-Deckert S., Couture C., Mustelin T., Altman A. Immunity 5:591-604(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SYK, MUTAGENESIS OF ARG-696.
[9]	"Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation." Bustelo X.R., Crespo P., Lopez-Barahona M., Gutkind J.S., Barbacid M. Oncogene 15:2511-2520(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CBLB.
[10]	"BLNK: a central linker protein in B cell activation." Fu C., Turck C.W., Kurosaki T., Chan A.C. Immunity 9:93-103(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BLNK; PLCG1; GRB2 AND NCK1.
[11]	"hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways." Germani A., Romero F., Houlard M., Camonis J., Gisselbrecht S., Fischer S., Varin-Blank N. Mol. Cell. Biol. 19:3798-3807(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SIAH2.
[12]	"T-cell receptor antagonists induce Vav phosphorylation by selective activation of Fyn kinase." Huang J., Tilly D., Altman A., Sugie K., Grey H.M. Proc. Natl. Acad. Sci. U.S.A. 97:10923-10929(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY FYN.
[13]	"DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines." Nishihara H., Maeda M., Oda A., Tsuda M., Sawa H., Nagashima K., Tanaka S. Blood 100:3968-3974(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DOCK2.
[14]	"Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells." Lindholm C.K., Henriksson M.L., Hallberg B., Welsh M. Eur. J. Biochem. 269:3279-3288(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SHB.
[15]	"Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity." Yabana N., Shibuya M. Oncogene 21:7720-7729(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APS.
[16]	"Kinase-independent functions for Itk in TCR-induced regulation of Vav and the actin cytoskeleton." Dombroski D., Houghtling R.A., Labno C.M., Precht P., Takesono A., Caplen N.J., Billadeau D.D., Wange R.L., Burkhardt J.K., Schwartzberg P.L. J. Immunol. 174:1385-1392(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ITK.
[17]	"Novel association of Vav2 and Nek3 modulates signaling through the human prolactin receptor." Miller S.L., DeMaria J.E., Freier D.O., Riegel A.M., Clevenger C.V. Mol. Endocrinol. 19:939-949(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NEK3.
[18]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-826, MASS SPECTROMETRY.
[19]	"Characterization of VIK-1: a new Vav-interacting Kruppel-like protein." Houlard M., Romero-Portillo F., Germani A., Depaux A., Regnier-Ricard F., Gisselbrecht S., Varin-Blank N. Oncogene 24:28-38(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZNF655/VIK.
[20]	"A Pyk2-Vav1 complex is recruited to beta3-adhesion sites to initiate Rho activation." Gao C., Blystone S.D. Biochem. J. 420:49-56(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTK2B/PYK2.
[21]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]	"Solution structure of the SH2 domain of human proto-oncogene protein VAV1." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 661-775.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
M59834 Genomic DNA. Translation: AAA63267.1.
X16316 mRNA. Translation: CAA34383.1. Frameshift.
X83931 mRNA. Translation: CAA58783.1.

IPI

IPI00011696.

PIR

TVHUVV. B39576.

RefSeq

NP_005419.2. NM_005428.3.

UniGene

Hs.116237.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CRH	NMR	-	A	629-775	[»]
2LCT	NMR	-	A	664-767	[»]
2ROR	NMR	-	A	629-775	[»]
3BJI	X-ray	2.60	A/B	189-565	[»]
3KY9	X-ray	2.73	A/B	2-584	[»]

ProteinModelPortal

P15498.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1061N.

IntAct

P15498. 3 interactions.

MINT

MINT-1211643.

STRING

9606.ENSP00000302269.

PTM databases

PhosphoSite

P15498.

Polymorphism databases

DMDM

13124807.

Proteomic databases

PaxDb

P15498.

PeptideAtlas

P15498.

PRIDE

P15498.

Protocols and materials databases

DNASU

7409.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000602142; ENSP00000472929; ENSG00000141968.

GeneID

7409.

KEGG

hsa:7409.

UCSC

uc002mfu.1. human.

Organism-specific databases

CTD

7409.

GeneCards

GC19P006772.

H-InvDB

HIX0202828.

HGNC

HGNC:12657. VAV1.

HPA

HPA001864.

MIM

164875. gene.

neXtProt

NX_P15498.

PharmGKB

PA37280.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG326494.

HOGENOM

HOG000234364.

HOVERGEN

HBG018066.

InParanoid

P15498.

KO

K05730.

OMA

HRVTWDG.

OrthoDB

EOG4XGZZJ.

PhylomeDB

P15498.

Enzyme and pathway databases

Pathway_Interaction_DB

pi3kcipathway. Class I PI3K signaling events.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
il6_7pathway. IL6-mediated signaling events.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.
REACT_85674. Hemostasis.

Gene expression databases

ArrayExpress

P15498.

Bgee

P15498.

CleanEx

HS_VAV1.

Genevestigator

P15498.

Family and domain databases

Gene3D

1.10.418.10. 1 hit.
1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
3.30.505.10. 1 hit.

InterPro

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.
IPR001452. SH3_domain.
IPR003096. SM22_calponin.
[Graphical view]

Pfam

PF00130. C1_1. 1 hit.
PF00307. CH. 1 hit.
PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 2 hits.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00888. SM22CALPONIN.

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.
[Graphical view]

SUPFAM

SSF47576. Calponin-homology. 1 hit.
SSF48065. DH-domain. 1 hit.
SSF50044. SH3. 2 hits.

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.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P15498.

GenomeRNAi

7409.

NextBio

29008.

PMAP-CutDB

P15498.

SOURCE

Search...

Entry information

Entry name

VAV_HUMAN

Accession

Primary (citable) accession number: P15498
Secondary accession number(s): Q15860

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	February 21, 2001
Last modified:	May 1, 2013
This is version 163 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.