Reviewed, UniProtKB/Swiss-Prot P52735 (VAV2_HUMAN)

Names and origin

Protein names

Recommended name:
    Guanine nucleotide exchange factor VAV2
      Short name=VAV-2

Gene names

Name:

VAV2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	878 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases.
Tissue specificity	Widely expressed.
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
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Phorbol-ester binding Repeat SH2 domain SH3 domain Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	intracellular signaling cascade Inferred from electronic annotation. Source: InterPro regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular function	Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NEK3	P51956	3	EBI-297549,EBI-476041
PRLR	P16471	1	EBI-297549,EBI-476182

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P52735-1)

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: P52735-2)

The sequence of this isoform differs from the canonical sequence as follows:
     185-189: Missing.
     470-474: Missing.

Isoform 3 (identifier: P52735-3)

The sequence of this isoform differs from the canonical sequence as follows:
     185-189: Missing.
     470-474: Missing.
     783-811: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 878

878

Guanine nucleotide exchange factor VAV2

PRO_0000080984

Regions

Domain

1 – 119

119

CH

Domain

198 – 376

179

DH

Domain

405 – 512

108

PH

Domain

586 – 652

67

SH3 1

Domain

673 – 767

95

SH2

Domain

816 – 877

62

SH3 2

Zinc finger

523 – 572

50

Phorbol-ester/DAG-type

Amino acid modifications

Modified residue

142

1

Phosphotyrosine; by EGFR Ref.7

Modified residue

159

1

Phosphotyrosine; by EGFR Ref.7

Modified residue

172

1

Phosphotyrosine; by EGFR Ref.7

Modified residue

576

1

Phosphoserine Ref.8

Modified residue

626

1

Phosphoserine Ref.8

Natural variations

Alternative sequence

185 – 189

5

Missing in isoform 2 and isoform 3.

VSP_034900

Alternative sequence

470 – 474

5

Missing in isoform 2 and isoform 3.

VSP_034901

Alternative sequence

783 – 811

29

Missing in isoform 3.

VSP_034902

Natural variant

594

1

M → V Ref.1 Ref.4

VAR_045690

Experimental info

Sequence conflict

241

1

F → L in CAE45861. Ref.5

Sequence conflict

254

1

F → L in CAE45861. Ref.5

Sequence conflict

877

1

I → T in CAE45861. Ref.5

Secondary structure

1

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878

Helix Strand Turn

Details...

Helix

668 – 670

3

Beta strand

674 – 677

4

Helix

680 – 689

10

Beta strand

694 – 698

5

Beta strand

707 – 712

6

Beta strand

714 – 725

12

Beta strand

728 – 731

4

Beta strand

737 – 739

3

Helix

740 – 747

8

Turn

752 – 755

4

Beta strand

819 – 825

7

Beta strand

842 – 844

3

Beta strand

847 – 854

8

Beta strand

856 – 860

5

Beta strand

863 – 867

5

Beta strand

869 – 874

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 22, 2008. Version 2. Checksum: C186911605FD5B73	FASTA	878	101,289
	10 20 30 40 50 60 MEQWRQCGRW LIDCKVLPPN HRVVWPSAVV FDLAQALRDG VLLCQLLHNL SPGSIDLKDI 70 80 90 100 110 120 NFRPQMSQFL CLKNIRTFLK VCHDKFGLRN SELFDPFDLF DVRDFGKVIS AVSRLSLHSI 130 140 150 160 170 180 AQNKGIRPFP SEETTENDDD VYRSLEELAD EHDLGEDIYD CVPCEDGGDD IYEDIIKVEV 190 200 210 220 230 240 QQPMIRYMQK MGMTEDDKRN CCLLEIQETE AKYYRTLEDI EKNYMSPLRL VLSPADMAAV 250 260 270 280 290 300 FINLEDLIKV HHSFLRAIDV SVMVGGSTLA KVFLDFKERL LIYGEYCSHM EHAQNTLNQL 310 320 330 340 350 360 LASREDFRQK VEECTLKVQD GKFKLQDLLV VPMQRVLKYH LLLKELLSHS AERPERQQLK 370 380 390 400 410 420 EALEAMQDLA MYINEVKRDK ETLRKISEFQ SSIENLQVKL EEFGRPKIDG ELKVRSIVNH 430 440 450 460 470 480 TKQDRYLFLF DKVVIVCKRK GYSYELKEII ELLFHKMTDD PMNNKDVKKS HGKMWSYGFY 490 500 510 520 530 540 LIHLQGKQGF QFFCKTEDMK RKWMEQFEMA MSNIKPDKAN ANHHSFQMYT FDKTTNCKAC 550 560 570 580 590 600 KMFLRGTFYQ GYMCTKCGVG AHKECLEVIP PCKFTSPADL DASGAGPGPK MVAMQNYHGN 610 620 630 640 650 660 PAPPGKPVLT FQTGDVLELL RGDPESPWWE GRLVQTRKSG YFPSSSVKPC PVDGRPPISR 670 680 690 700 710 720 PPSREIDYTA YPWFAGNMER QQTDNLLKSH ASGTYLIRER PAEAERFAIS IKFNDEVKHI 730 740 750 760 770 780 KVVEKDNWIH ITEAKKFDSL LELVEYYQCH SLKESFKQLD TTLKYPYKSR ERSASRASSR 790 800 810 820 830 840 SPASCASYNF SFLSPQGLSF ASQGPSAPFW SVFTPRVIGT AVARYNFAAR DMRELSLREG 850 860 870 DVVRIYSRIG GDQGWWKGET NGRIGWFPST YVEEEGIQ
	Isoform 2. Checksum: 6C67C472825D2DFD	FASTA	868	100,057
	10 20 30 40 50 60 MEQWRQCGRW LIDCKVLPPN HRVVWPSAVV FDLAQALRDG VLLCQLLHNL SPGSIDLKDI 70 80 90 100 110 120 NFRPQMSQFL CLKNIRTFLK VCHDKFGLRN SELFDPFDLF DVRDFGKVIS AVSRLSLHSI 130 140 150 160 170 180 AQNKGIRPFP SEETTENDDD VYRSLEELAD EHDLGEDIYD CVPCEDGGDD IYEDIIKVEV 190 200 210 220 230 240 QQPMKMGMTE DDKRNCCLLE IQETEAKYYR TLEDIEKNYM SPLRLVLSPA DMAAVFINLE 250 260 270 280 290 300 DLIKVHHSFL RAIDVSVMVG GSTLAKVFLD FKERLLIYGE YCSHMEHAQN TLNQLLASRE 310 320 330 340 350 360 DFRQKVEECT LKVQDGKFKL QDLLVVPMQR VLKYHLLLKE LLSHSAERPE RQQLKEALEA 370 380 390 400 410 420 MQDLAMYINE VKRDKETLRK ISEFQSSIEN LQVKLEEFGR PKIDGELKVR SIVNHTKQDR 430 440 450 460 470 480 YLFLFDKVVI VCKRKGYSYE LKEIIELLFH KMTDDPMNNK DVKKWSYGFY LIHLQGKQGF 490 500 510 520 530 540 QFFCKTEDMK RKWMEQFEMA MSNIKPDKAN ANHHSFQMYT FDKTTNCKAC KMFLRGTFYQ 550 560 570 580 590 600 GYMCTKCGVG AHKECLEVIP PCKFTSPADL DASGAGPGPK MVAMQNYHGN PAPPGKPVLT 610 620 630 640 650 660 FQTGDVLELL RGDPESPWWE GRLVQTRKSG YFPSSSVKPC PVDGRPPISR PPSREIDYTA 670 680 690 700 710 720 YPWFAGNMER QQTDNLLKSH ASGTYLIRER PAEAERFAIS IKFNDEVKHI KVVEKDNWIH 730 740 750 760 770 780 ITEAKKFDSL LELVEYYQCH SLKESFKQLD TTLKYPYKSR ERSASRASSR SPASCASYNF 790 800 810 820 830 840 SFLSPQGLSF ASQGPSAPFW SVFTPRVIGT AVARYNFAAR DMRELSLREG DVVRIYSRIG 850 860 GDQGWWKGET NGRIGWFPST YVEEEGIQ
	Isoform 3. Checksum: 21910D516F4A211D	FASTA	839	97,032
	10 20 30 40 50 60 MEQWRQCGRW LIDCKVLPPN HRVVWPSAVV FDLAQALRDG VLLCQLLHNL SPGSIDLKDI 70 80 90 100 110 120 NFRPQMSQFL CLKNIRTFLK VCHDKFGLRN SELFDPFDLF DVRDFGKVIS AVSRLSLHSI 130 140 150 160 170 180 AQNKGIRPFP SEETTENDDD VYRSLEELAD EHDLGEDIYD CVPCEDGGDD IYEDIIKVEV 190 200 210 220 230 240 QQPMKMGMTE DDKRNCCLLE IQETEAKYYR TLEDIEKNYM SPLRLVLSPA DMAAVFINLE 250 260 270 280 290 300 DLIKVHHSFL RAIDVSVMVG GSTLAKVFLD FKERLLIYGE YCSHMEHAQN TLNQLLASRE 310 320 330 340 350 360 DFRQKVEECT LKVQDGKFKL QDLLVVPMQR VLKYHLLLKE LLSHSAERPE RQQLKEALEA 370 380 390 400 410 420 MQDLAMYINE VKRDKETLRK ISEFQSSIEN LQVKLEEFGR PKIDGELKVR SIVNHTKQDR 430 440 450 460 470 480 YLFLFDKVVI VCKRKGYSYE LKEIIELLFH KMTDDPMNNK DVKKWSYGFY LIHLQGKQGF 490 500 510 520 530 540 QFFCKTEDMK RKWMEQFEMA MSNIKPDKAN ANHHSFQMYT FDKTTNCKAC KMFLRGTFYQ 550 560 570 580 590 600 GYMCTKCGVG AHKECLEVIP PCKFTSPADL DASGAGPGPK MVAMQNYHGN PAPPGKPVLT 610 620 630 640 650 660 FQTGDVLELL RGDPESPWWE GRLVQTRKSG YFPSSSVKPC PVDGRPPISR PPSREIDYTA 670 680 690 700 710 720 YPWFAGNMER QQTDNLLKSH ASGTYLIRER PAEAERFAIS IKFNDEVKHI KVVEKDNWIH 730 740 750 760 770 780 ITEAKKFDSL LELVEYYQCH SLKESFKQLD TTLKYPYKSR ERSASRASSR SPVFTPRVIG 790 800 810 820 830 TAVARYNFAA RDMRELSLRE GDVVRIYSRI GGDQGWWKGE TNGRIGWFPS TYVEEEGIQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of VAV2 on 9q34 and its exclusion as the tuberous sclerosis gene TSC1." Henske E.P., Short M.P., Jozwiak S., Bovey C.M., Ramlakhan S., Haines J.L., Kwiatkowski D.J. Ann. Hum. Genet. 59:25-37(1995) [PubMed: 7762982] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-594. Tissue: Brain.
[2]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT VAL-594. Tissue: Kidney.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 39-878 (ISOFORM 3). Tissue: Rectum tumor.
[6]	"Transcript variant of VAV2 gene in tumoral cell lines (FaDu, HEp2, HeLa and Siha)." Mancini U.M., Tajara E.H. Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 453-506 (ISOFORM 2/3).
[7]	"Mechanism of epidermal growth factor regulation of Vav2, a guanine nucleotide exchange factor for Rac." Tamas P., Solti Z., Bauer P., Illes A., Sipeki S., Bauer A., Farago A., Downward J., Buday L. J. Biol. Chem. 278:5163-5171(2003) [PubMed: 12454019] [Abstract] Cited for: PHOSPHORYLATION AT TYR-142; TYR-159 AND TYR-172.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576 AND SER-626, MASS SPECTROMETRY.
[9]	"Solution structure of the SH2 domain and of the second SH3 domain of human protein VAV-2." RIKEN structural genomics initiative (RSGI) Submitted (APR-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 663-878.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

S76992 mRNA. Translation: AAB34377.1.
AL590710, AL357934, AL445931 Genomic DNA. Translation: CAI12279.1.
AL445931, AL357934, AL590710 Genomic DNA. Translation: CAI13722.1.
AL357934, AL445931, AL590710 Genomic DNA. Translation: CAI15783.1.
AL590710, AL357934, AL445931 Genomic DNA. Translation: CAI12278.1.
AL445931, AL357934, AL590710 Genomic DNA. Translation: CAI13723.1.
AL357934, AL445931, AL590710 Genomic DNA. Translation: CAI15781.1.
AL590710, AL357934, AL445931 Genomic DNA. Translation: CAI12280.1.
AL445931, AL357934, AL590710 Genomic DNA. Translation: CAI13724.1.
AL357934, AL445931, AL590710 Genomic DNA. Translation: CAI15782.1.
CH471090 Genomic DNA. Translation: EAW88108.1.
BC033187 mRNA. Translation: AAH33187.1.
BC132965 mRNA. Translation: AAI32966.1.
BC132967 mRNA. Translation: AAI32968.1.
BX640754 mRNA. Translation: CAE45861.1.
AY563001 mRNA. Translation: AAS75591.1.

IPI

IPI00004977.
IPI00472451.
IPI00872160.

PIR

I51940.

RefSeq

NP_001127870.1.
NP_003362.2.

UniGene

Hs.369921
Hs.689325

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DLZ	NMR	-	A	663-767	[»]
2DM1	NMR	-	A	819-878	[»]

SMR

P52735. Positions 1-131.

ModBase

Search...

Protein-protein interaction databases

IntAct

P52735. 3 interactions.

PTM databases

PhosphoSite

P52735.

Genome annotation databases

Ensembl

ENSG00000160293. Homo sapiens. [Contig view]

GeneID

7410.

KEGG

hsa:7410.

Organism-specific databases

GeneCards

GC09M135616.

H-InvDB

HIX0008512.

HGNC

HGNC:12658. VAV2.

HPA

HPA003224.

MIM

600428. gene.

PharmGKB

PA37281.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P52735.

OMA

P52735. PGPKMVA.

Enzyme and pathway databases

Pathway_Interaction_DB

bcr_5pathway. BCR signaling pathway.
epha_fwdpathway. EPHA forward signaling.
epha2_fwdpathway. EPHA2 forward signaling.
epopathway. EPO signaling pathway.
pdgfrbpathway. PDGFR-beta signaling pathway.

Reactome

REACT_11044. Signaling by Rho GTPases.

Gene expression databases

ArrayExpress

P52735.

Bgee

P52735.

GermOnline

ENSG00000160293. Homo sapiens.

Family and domain databases

InterPro

IPR001715. Calponin_act_bd.
IPR002219. DAG_PE_bd.
IPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR001849. Pleckstrin_homology.
IPR000980. SH2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]

Gene3D

G3DSA:1.10.418.10. Calponin-homology. 1 hit.
G3DSA:1.20.900.10. RhoGEF. 1 hit.
G3DSA:3.30.505.10. SH2. 1 hit.

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. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.

ProDom

PD000093. SH2. 1 hit.
PD000066. SH3. 1 hit.
[Graphical view] [Entries sharing at least one domain]

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]

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 Resources

NextBio

29012.

SOURCE

Search...

Entry information

Entry name

VAV2_HUMAN

Accession

Primary (citable) accession number: P52735
Secondary accession number(s): A2RUM4 , A8MQ12, Q5SYV3, Q5SYV4, Q5SYV5, Q6N012, Q6PIJ9, Q6Q317

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 22, 2008
Last modified:	June 16, 2009
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)