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P70460 (VASP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Vasodilator-stimulated phosphoprotein

Short name=VASP
Gene names
Name:Vasp
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length375 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration. VASP promotes actin filament elongation. It protects the barbed end of growing actin filaments against capping and increases the rate of actin polymerization in the presence of capping protein. VASP stimulates actin filament elongation by promoting the transfer of profilin-bound actin monomers onto the barbed end of growing actin filaments. Plays a role in actin-based mobility of Listeria monocytogenes in host cells. Regulates actin dynamics in platelets and plays an important role in regulating platelet aggregation By similarity. Ref.6

Subunit structure

Homotetramer By similarity. Interacts with PFN1, PFN2, LPP, ACTN1 and ACTG1. Interacts, via the EVH1 domain, with the Pro-rich regions of ZYX. This interaction is important for targeting to focal adhesions and the formation of actin-rich structures at the apical surface of cells. Interacts, via the EVH1 domain, with the Pro-rich domain of Listeria monocytogenes actA. Interacts with APBB1IP. Interacts, via the Pro-rich domain, with the C-terminal SH3 domain of DNMBP. Interacts weakly with MEFV By similarity. Ref.7 Ref.8 Ref.9 Ref.10

Subcellular location

Cytoplasm. Cytoplasmcytoskeleton. Cell junctionfocal adhesion. Cell junctiontight junction By similarity. Cell projectionlamellipodium membrane. Cell projectionfilopodium membrane. Note: Targeted to stress fibers and focal adhesions through interaction with a number of proteins including MRL family members. Localizes to the plasma membrane in protruding lamellipodia and filopodial tips. Stimulation by thrombin or PMA, also translocates VASP to focal adhesions. Localized along the sides of actin filaments throughout the peripheral cytoplasm under basal conditions By similarity. In pre-apoptotic cells, colocalizes with MEFV in large specks (pyroptosomes) By similarity. Ref.6

Tissue specificity

Highly expressed in thymus and spleen. Lower levels in lung, ovary, placenta and fat. Ref.5

Developmental stage

Expressed constantly throughout brain development, with lower levels in adulthood. Ref.5

Domain

The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization.

The WH1 domain mediates interaction with XIRP1 By similarity.

Post-translational modification

Major substrate for cAMP-dependent (PKA) and cGMP-dependent protein kinase (PKG) in platelets. The preferred site for PKA is Ser-153, the preferred site for PKG, Ser-235. In ADP-activated platelets, phosphorylation by PKA or PKG/PRKG1 on Ser-153 leads to fibrinogen receptor inhibition. Phosphorylation on Thr-274 requires prior phosphorylation on Ser-153 and Ser-235. In response to phorbol ester (PMA) stimulation, phosphorylated by PKC/PRKCA. In response to thrombin, phosphorylated by both PKC and ROCK1. Phosphorylation at Thr-274 by AMPK does not require prior phosphorylation at Ser-153 or Ser-235. Phosphorylation at Ser-153 by PKA is required for localization to the tight junctions in epithelial cells. Phosphorylation modulates F-actin binding, actin filament elongation and platelet activation. Phosphorylation at Ser-318 by AMPK also alters actin filament binding. Carbon monoxide (CO) promotes phosphorylation at Ser-153, while nitric oxide (NO) promotes phosphorylation at Ser-153, but also at Ser-235. Ref.2 Ref.7 Ref.8 Ref.13

Sequence similarities

Belongs to the Ena/VASP family.

Contains 1 WH1 domain.

Sequence caution

The sequence CAA67108.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Tight junction
   Coding sequence diversityPolymorphism
   DomainCoiled coil
Repeat
SH3-binding
   LigandActin-binding
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from genetic interaction PubMed 15371503. Source: MGI

actin polymerization or depolymerization

Inferred from electronic annotation. Source: InterPro

axon guidance

Inferred from genetic interaction PubMed 15371503. Source: MGI

neural tube closure

Inferred from genetic interaction PubMed 15371503. Source: MGI

protein homotetramerization

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

filopodium

Inferred from direct assay PubMed 15148305PubMed 15294161. Source: MGI

filopodium membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

focal adhesion

Inferred from direct assay PubMed 15148305. Source: MGI

lamellipodium

Inferred from direct assay PubMed 15148305. Source: MGI

lamellipodium membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

tight junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 15465019. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 375374Vasodilator-stimulated phosphoprotein
PRO_0000065768

Regions

Domain2 – 113112WH1
Repeat340 – 354151
Repeat355 – 369152
Region221 – 373153EVH2
Region221 – 24121EVH2 block A
Region257 – 27418EVH2 block B
Region338 – 37235EVH2 block C
Region339 – 368302 X 15 AA tandem repeats of L-[EQ]-[KR] [MV]-K-[EQ]-E-[IL]-[IL]-E-[AEV]-[FV]-[KRV]-[KQ]-E
Coiled coil337 – 36731 Potential
Motif230 – 2334KLKR
Compositional bias166 – 18217Poly-Pro
Compositional bias317 – 3204Poly-Ser

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue391Phosphotyrosine By similarity
Modified residue1531Phosphoserine; by PKA, PKC, PKG/PRKG1 and ROCK1 Ref.7
Modified residue2351Phosphoserine; by PKA and PKG Ref.7
Modified residue2741Phosphothreonine; by PKA, PKG/PRKG1 and AMPK By similarity
Modified residue2791N6-acetyllysine By similarity
Modified residue3111Phosphothreonine By similarity
Modified residue3171Phosphoserine By similarity
Modified residue3181Phosphoserine; by AMPK Ref.13

Natural variations

Natural variant2091A → T. Ref.1 Ref.3

Experimental info

Mutagenesis1531S → D: Reduces actin polymerization to a lesser extent than wild-type. Greater effect on actin polymerization; when associated with D-235 and E-274. Ref.7 Ref.8
Mutagenesis232 – 2332RK → GE or EE: Reduced binding to monomeric actin. No VASP-induced actin polymerization. Ref.8
Mutagenesis2351S → D: Reduces actin polymerization to a lesser extent than wild-type. Ref.7 Ref.8
Mutagenesis2741T → E: Reduces actin polymerization to a lesser extent than wild-type. Ref.7 Ref.8
Sequence conflict106 – 11510Missing in BAE42025. Ref.3
Sequence conflict2371Missing in BAE33933. Ref.3
Sequence conflict3371S → Y in BAE29310. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P70460 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 19369286CF4276C7

FASTA37539,667
        10         20         30         40         50         60 
MSETVICSSR ATVMLYDDSN KRWLPAGTGP QAFSRVQIYH NPTANSFRVV GRKMQPDQQV 

        70         80         90        100        110        120 
VINCAIIRGV KYNQATPIFH QWRDARQVWG LNFGSKEDAI QFATGMANAL EALEGGGPPP 

       130        140        150        160        170        180 
APAPPAWSAQ NGPSPEELEQ QKRQPEHMER RVSNAGGPPA PPAGGPPPPP GPPPPPGPPP 

       190        200        210        220        230        240 
PPGLPSSGVS GAGHGAGAAP PPAPPLPTAQ GPNSGGSGAP GLAAAIAGAK LRKVSKQEEA 

       250        260        270        280        290        300 
SGGPLAPKAE NSRSTGGGLM EEMNAMLARR RKATQVGEKP PKDESASEES EARLPAQSEP 

       310        320        330        340        350        360 
VRRPWEKNST TLPRMKSSSS VTTSEAHPST PCSSDDSDLE RVKQELLEEV RKELQKMKEE 

       370 
IIEVFVQELR KRGSP 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of the VASP (vasodilator-stimulated phosphoprotein) genes in human and mouse: structure, sequence, and chromosomal localization."
Zimmer M., Fink T., Fischer L., Hauser W., Scherer K., Lichter P., Walter U.
Genomics 36:227-233(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-209.
Strain: 129.
[2]"Cyclic AMP- and cyclic GMP-dependent protein kinases differ in their regulation of cyclic AMP response element-dependent gene transcription."
Collins S.P., Uhler M.D.
J. Biol. Chem. 274:8391-8404(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION.
Strain: C57BL/6J.
[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. expand/collapse author list , 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], VARIANT THR-209.
Strain: C57BL/6J and NOD.
Tissue: Adipose tissue, Bone marrow, Dendritic cell and Spleen.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Kidney and Mammary tumor.
[5]"Mena is required for neurulation and commissure formation."
Lanier L.M., Gates M.A., Witke W., Menzies A.S., Wehman A.M., Macklis J.D., Kwiatkowski D., Soriano P., Gertler F.B.
Neuron 22:313-325(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
[6]"Directed actin polymerization is the driving force for epithelial cell-cell adhesion."
Vasioukhin V., Bauer C., Yin M., Fuchs E.
Cell 100:209-219(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]"Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its interaction with actin."
Harbeck B., Huttelmaier S., Schlueter K., Jockusch B.M., Illenberger S.
J. Biol. Chem. 275:30817-30825(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ACTN1; PFN1; PFN2; VCL AND ZYX, PHOSPHORYLATION AT SER-153 AND SER-235, MUTAGENESIS OF SER-153; SER-235 AND THR-274.
[8]"The vasodilator-stimulated phosphoprotein promotes actin polymerisation through direct binding to monomeric actin."
Walders-Harbeck B., Khaitlina S.Y., Hinssen H., Jockusch B.M., Illenberger S.
FEBS Lett. 529:275-280(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ACTG1, PHOSPHORYLATION, MUTAGENESIS OF 232-ARG-LYS-233.
[9]"Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology domains, links dynamin to regulation of the actin cytoskeleton."
Salazar M.A., Kwiatkowski A.V., Pellegrini L., Cestra G., Butler M.H., Rossman K.L., Serna D.M., Sondek J., Gertler F.B., De Camilli P.
J. Biol. Chem. 278:49031-49043(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DNMBP.
[10]"PREL1 provides a link from Ras signalling to the actin cytoskeleton via Ena/VASP proteins."
Jenzora A., Behrendt B., Small J.V., Wehland J., Stradal T.E.
FEBS Lett. 579:455-463(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APBB1IP.
[11]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[12]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Phosphorylation of VASP by AMPK alters actin binding and occurs at a novel site."
Thomson D.M., Ascione M.P., Grange J., Nelson C., Hansen M.D.
Biochem. Biophys. Res. Commun. 414:215-219(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-318.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X98475 Genomic DNA. Translation: CAA67108.1. Sequence problems.
AF084548 mRNA. Translation: AAD16045.1.
AK140329 mRNA. Translation: BAE24338.1.
AK150103 mRNA. Translation: BAE29310.1.
AK157021 mRNA. Translation: BAE33933.1.
AK170780 mRNA. Translation: BAE42025.1.
AK171715 mRNA. Translation: BAE42628.1.
BC010223 mRNA. Translation: AAH10223.1.
BC015289 mRNA. Translation: AAH15289.1.
CCDSCCDS52056.1.
RefSeqNP_001268950.1. NM_001282021.1.
NP_001268951.1. NM_001282022.1.
NP_033525.2. NM_009499.3.
UniGeneMm.9684.

3D structure databases

ProteinModelPortalP70460.
SMRP70460. Positions 1-115, 333-372.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204499. 2 interactions.
IntActP70460. 3 interactions.
MINTMINT-1215713.

PTM databases

PhosphoSiteP70460.

Proteomic databases

MaxQBP70460.
PaxDbP70460.
PRIDEP70460.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000032561; ENSMUSP00000032561; ENSMUSG00000030403.
GeneID22323.
KEGGmmu:22323.
UCSCuc009fle.2. mouse.

Organism-specific databases

CTD7408.
MGIMGI:109268. Vasp.

Phylogenomic databases

eggNOGNOG265043.
GeneTreeENSGT00730000110272.
HOVERGENHBG006655.
InParanoidP70460.
KOK06274.
OMAQPEHMER.
OrthoDBEOG72JWGQ.
PhylomeDBP70460.
TreeFamTF321411.

Gene expression databases

BgeeP70460.
CleanExMM_VASP.
GenevestigatorP70460.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR011993. PH_like_dom.
IPR017354. Vasodilator_phosphoprotein.
IPR014885. VASP_tetra.
IPR000697. WH1/EVH1.
[Graphical view]
PfamPF08776. VASP_tetra. 1 hit.
PF00568. WH1. 1 hit.
[Graphical view]
PIRSFPIRSF038010. Vasodilator_Phospo. 1 hit.
SMARTSM00461. WH1. 1 hit.
[Graphical view]
PROSITEPS50229. WH1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSVASP. mouse.
NextBio302545.
PROP70460.
SOURCESearch...

Entry information

Entry nameVASP_MOUSE
AccessionPrimary (citable) accession number: P70460
Secondary accession number(s): Q3TAP0 expand/collapse secondary AC list , Q3TCD2, Q3U0C2, Q3UDF1, Q91VD2, Q9R214
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 121 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot