P27870 (VAV_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proto-oncogene vav

Alternative name(s):
p95vav

Gene names

Name:	Vav1
Synonyms:	Vav

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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	Interacts with SHB 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. May interact with CCPG1. Interacts with CLNK. Interacts with THEMIS2. Interacts with NEK3 and this interaction is prolactin-dependent. Interacts with ITK. Interacts with PTK2B/PYK2 By similarity. Interacts with HCK. Interacts with PTK2B/PYK2. Interacts (via SH2 domain) with SYK By similarity. Interacts with ANKRD54. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14
Tissue specificity	Widely expressed in hematopoietic cells but not in other cell types. Found in the spleen and lung. Ref.1
Domain	The DH domain is involved in interaction with CCPG1.
Post-translational modification	Phosphorylated by FYN By similarity. Phosphorylated on tyrosine residues by HCK in response to IFNG and bacterial lipopolysaccharide (LPS). Ref.6 Ref.8 Ref.9
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
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 differentiation Traceable author statement PubMed 11070165. Source: MGI immune response Inferred from mutant phenotype PubMed 11070165. Source: MGI integrin-mediated signaling pathway Inferred from genetic interaction PubMed 15249579. Source: MGI intracellular signal transduction Inferred from mutant phenotype PubMed 11070165. Source: MGI phagocytosis Inferred from genetic interaction PubMed 15249579. Source: MGI positive regulation of cell adhesion Inferred from genetic interaction PubMed 15249579. Source: MGI regulation of GTPase activity Inferred from genetic interaction PubMed 15249579. Source: MGI regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	Rac guanyl-nucleotide exchange factor activity Inferred from genetic interaction PubMed 15249579. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 845

845

Proto-oncogene vav

PRO_0000080981

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 By similarity

Modified residue

844

1

Phosphotyrosine Ref.12

Experimental info

Mutagenesis

529

1

C → S: Abolishes transforming activity. Ref.1

Mutagenesis

532

1

C → S: Abolishes transforming activity. Ref.1

Mutagenesis

554

1

H → D: Abolishes transforming activity. Ref.1

Sequence conflict

29

1

Q → E in AAA63402. Ref.4

Sequence conflict

226

1

R → L in BAC40436. Ref.3

Secondary structure

1

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845

Helix Strand Turn

Details...

Helix

170 – 177

8

Turn

178 – 180

3

Helix

191 – 219

29

Helix

221 – 224

4

Turn

225 – 227

3

Helix

230 – 237

8

Helix

240 – 259

20

Helix

261 – 263

3

Helix

266 – 273

8

Helix

276 – 278

3

Helix

279 – 300

22

Helix

302 – 316

15

Helix

322 – 325

4

Helix

328 – 333

6

Helix

336 – 346

11

Helix

350 – 389

40

Beta strand

390 – 392

3

Helix

397 – 400

4

Beta strand

402 – 412

11

Beta strand

420 – 437

18

Beta strand

440 – 448

9

Turn

449 – 451

3

Beta strand

452 – 455

4

Beta strand

469 – 475

7

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 – 541

4

Beta strand

543 – 546

4

Turn

547 – 549

3

Helix

555 – 560

6

Turn

585 – 587

3

Beta strand

596 – 599

4

Beta strand

603 – 607

5

Helix

610 – 612

3

Beta strand

624 – 629

6

Beta strand

635 – 641

7

Turn

642 – 644

3

Beta strand

647 – 651

5

Helix

652 – 654

3

Beta strand

655 – 657

3

Beta strand

786 – 791

6

Beta strand

796 – 800

5

Beta strand

808 – 813

6

Beta strand

817 – 825

9

Beta strand

828 – 833

6

Beta strand

836 – 841

6

Sequences

	Sequence		Length	Mass (Da)
	P27870 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 3666DCCD1C5229DA	FASTA	845	98,137
	10 20 30 40 50 60 MELWRQCTHW LIQCRVLPPS HRVTWEGAQV CELAQALRDG VLLCQLLNNL LPQAINLREV 70 80 90 100 110 120 NLRPQMSQFL CLKNIRTFLS TCCEKFGLKR SELFEAFDLF DVQDFGKVIY TLSALSWTPI 130 140 150 160 170 180 AQNKGIMPFP TEDSALNDED IYSGLSDQID DTAEEDEDLY DCVENEEAEG DEIYEDLMRL 190 200 210 220 230 240 ESVPTPPKMT EYDKRCCCLR EIQQTEEKYT DTLGSIQQHF MKPLQRFLKP QDMETIFVNI 250 260 270 280 290 300 EELFSVHTHF LKELKDALAG PGATTLYQVF IKYKERFLVY GRYCSQVESA SKHLDQVATA 310 320 330 340 350 360 REDVQMKLEE CSQRANNGRF TLRDLLMVPM QRVLKYHLLL QELVKHTQDA TEKENLRLAL 370 380 390 400 410 420 DAMRDLAQCV NEVKRDNETL RQITNFQLSI ENLDQSLANY GRPKIDGELK ITSVERRSKT 430 440 450 460 470 480 DRYAFLLDKA LLICKRRGDS YDLKASVNLH SFQVRDDSSG ERDNKKWSHM FLLIEDQGAQ 490 500 510 520 530 540 GYELFFKTRE LKKKWMEQFE MAISNIYPEN ATANGHDFQM FSFEETTSCK ACQMLLRGTF 550 560 570 580 590 600 YQGYRCYRCR APAHKECLGR VPPCGRHGQD FAGTMKKDKL HRRAQDKKRN ELGLPKMEVF 610 620 630 640 650 660 QEYYGIPPPP GAFGPFLRLN PGDIVELTKA EAEHNWWEGR NTATNEVGWF PCNRVHPYVH 670 680 690 700 710 720 GPPQDLSVHL WYAGPMERAG AEGILTNRSD GTYLVRQRVK DTAEFAISIK YNVEVKHIKI 730 740 750 760 770 780 MTSEGLYRIT EKKAFRGLLE LVEFYQQNSL KDCFKSLDTT LQFPYKEPER RAISKPPAGS 790 800 810 820 830 840 TKYFGTAKAR YDFCARDRSE LSLKEGDIIK ILNKKGQQGW WRGEIYGRIG WFPSNYVEED 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], TISSUE SPECIFICITY, MUTAGENESIS OF CYS-529; CYS-532 AND HIS-554.
[2]	"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: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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. , 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]. Strain: NOD. Tissue: Thymus.
[4]	"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 [MRNA] OF 1-93.
[5]	"Tec protein tyrosine kinase is involved in the signaling mechanism of granulocyte colony-stimulating factor receptor." Miyazato A., Yamashita Y., Hatake K., Miura Y., Ozawa K., Mano H. Cell Growth Differ. 7:1135-1139(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TEC.
[6]	"Bacterial LPS and IFN-gamma trigger the tyrosine phosphorylation of vav in macrophages: evidence for involvement of the hck tyrosine kinase." English B.K., Orlicek S.L., Mei Z., Meals E.A. J. Leukoc. Biol. 62:859-864(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCK, PHOSPHORYLATION.
[7]	"Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling." Sosinowski T., Pandey A., Dixit V.M., Weiss A. J. Exp. Med. 191:463-474(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SLA.
[8]	"Cbl-b regulates the CD28 dependence of T-cell activation." Chiang Y.J., Kole H.K., Brown K., Naramura M., Fukuhara S., Hu R.-J., Jang I.K., Gutkind J.S., Shevach E., Gu H. Nature 403:216-220(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH CBLB.
[9]	"Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b." Bachmaier K., Krawczyk C., Kozieradzki I., Kong Y.-Y., Sasaki T., Oliveira-dos-Santos A., Mariathasan S., Bouchard D., Wakeham A., Itie A., Le J., Ohashi P.S., Sarosi I., Nishina H., Lipkowitz S., Penninger J.M. Nature 403:211-216(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH CBLB.
[10]	"MIST functions through distinct domains in immunoreceptor signaling in the presence and absence of LAT." Goitsuka R., Tatsuno A., Ishiai M., Kurosaki T., Kitamura D. J. Biol. Chem. 276:36043-36050(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CLNK.
[11]	"Ccpg1, a novel scaffold protein that regulates the activity of the Rho guanine nucleotide exchange factor Dbs." Kostenko E.V., Olabisi O.O., Sahay S., Rodriguez P.L., Whitehead I.P. Mol. Cell. Biol. 26:8964-8975(2006) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INTERACTION WITH CCPG1.
[12]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-844, MASS SPECTROMETRY. Tissue: Mast cell.
[13]	"Liar, a novel Lyn-binding nuclear/cytoplasmic shuttling protein that influences erythropoietin-induced differentiation." Samuels A.L., Klinken S.P., Ingley E. Blood 113:3845-3856(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ANKRD54.
[14]	"Themis2/ICB1 is a signaling scaffold that selectively regulates macrophage Toll-like receptor signaling and cytokine production." Peirce M.J., Brook M., Morrice N., Snelgrove R., Begum S., Lanfrancotti A., Notley C., Hussell T., Cope A.P., Wait R. PLoS ONE 5:E11465-E11465(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH THEMIS2.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X64361 mRNA. Translation: CAA45713.1.
AK088586 mRNA. Translation: BAC40436.1.
M59833 mRNA. Translation: AAA63402.1.

IPI

IPI00322118.

PIR

TVMSVV. A61187.

RefSeq

NP_035821.3. NM_011691.4.

UniGene

Mm.248172.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F5X	NMR	-	A	170-375	[»]
1GCP	X-ray	2.10	A/B/C/D	595-660	[»]
1GCQ	X-ray	1.68	C	595-660	[»]
1K1Z	NMR	-	A	583-660	[»]
2KBT	NMR	-	A	784-844	[»]
2VRW	X-ray	1.85	B	170-575	[»]

ProteinModelPortal

P27870.

SMR

P27870. Positions 2-565, 596-779, 784-844.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31010N.

IntAct

P27870. 5 interactions.

MINT

MINT-85069.

PTM databases

PhosphoSite

P27870.

Proteomic databases

PaxDb

P27870.

PRIDE

P27870.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000005889; ENSMUSP00000005889; ENSMUSG00000034116.

GeneID

22324.

KEGG

mmu:22324.

Organism-specific databases

CTD

7409.

MGI

MGI:98923. Vav1.

Phylogenomic databases

eggNOG

NOG326494.

HOGENOM

HOG000234364.

HOVERGEN

HBG018066.

InParanoid

P27870.

KO

K05730.

OMA

HRVTWDG.

Enzyme and pathway databases

Reactome

REACT_89750. Hemostasis.

Gene expression databases

ArrayExpress

P27870.

Bgee

P27870.

CleanEx

MM_VAV1.

Genevestigator

P27870.

GermOnline

ENSMUSG00000034116. Mus musculus.

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

IPR022613. 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.
[Graphical view]

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.
[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

P27870.

NextBio

302549.

SOURCE

Search...

Entry information

Entry name

VAV_MOUSE

Accession

Primary (citable) accession number: P27870
Secondary accession number(s): Q8BTV7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	April 3, 2013
This is version 145 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program