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Protein

Vasodilator-stimulated phosphoprotein

Gene

VASP

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

Functioni

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.5 Publications

Miscellaneous

VASP phosphorylation is used to monitor the effect of so-called antiplatelet drugs that reduce platelet reactivity and are used to prevent stent thrombosis, strokes and heart attacks in patients at risk for these problems.

GO - Molecular functioni

  • actin binding Source: UniProtKB-KW
  • cadherin binding Source: BHF-UCL
  • profilin binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionActin-binding

Enzyme and pathway databases

ReactomeiR-HSA-202433 Generation of second messenger molecules
R-HSA-376176 Signaling by ROBO receptors
R-HSA-446353 Cell-extracellular matrix interactions
SIGNORiP50552

Protein family/group databases

MoonDBiP50552 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Vasodilator-stimulated phosphoprotein
Short name:
VASP
Gene namesi
Name:VASP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000125753.13
HGNCiHGNC:12652 VASP
MIMi601703 gene
neXtProtiNX_P50552

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

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Tight junction

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi157S → A: Promotes F-actin assembly; when associated with A-239 and A-278. Interferes with F-actin assembly; when associated with A-239 and E-278. 1 Publication1
Mutagenesisi239S → A: Promotes F-actin assembly; when associated with A-157 and A-278. Interferes with F-actin assembly; when associated with A-157 and E-278. 1 Publication1
Mutagenesisi278T → A: Promotes F-actin assembly; when associated with A-157 and A-239. 1 Publication1
Mutagenesisi278T → E: Interferes with F-actin assembly; when associated with A-157 and A-239. 1 Publication1
Mutagenesisi370F → A: Lower stability of tetramerization domain. 1 Publication1
Mutagenesisi370F → I or K: No change in stability of tetramerization domain. 1 Publication1

Organism-specific databases

DisGeNETi7408
OpenTargetsiENSG00000125753
PharmGKBiPA37276

Polymorphism and mutation databases

BioMutaiVASP
DMDMi1718079

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000657672 – 380Vasodilator-stimulated phosphoproteinAdd BLAST379

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei39PhosphotyrosineCombined sources1
Modified residuei46PhosphoserineCombined sources1
Modified residuei157Phosphoserine; by PKA, PKC, PKG/PRKG1 and ROCK14 Publications1
Modified residuei239Phosphoserine; by PKA and PKG/PRKG1Combined sources2 Publications1
Modified residuei278Phosphothreonine; by PKA, PKG/PRKG1 and AMPK2 Publications1
Modified residuei283N6-acetyllysineCombined sources1
Modified residuei284PhosphothreonineCombined sources1
Modified residuei305PhosphoserineCombined sources1
Modified residuei314PhosphoserineCombined sources1
Modified residuei316PhosphothreonineCombined sources1
Modified residuei322Phosphoserine; by AMPKCombined sources1
Modified residuei323PhosphoserineBy similarity1
Modified residuei325PhosphoserineBy similarity1

Post-translational modificationi

Major substrate for cAMP-dependent (PKA) and cGMP-dependent protein kinase (PKG) in platelets. The preferred site for PKA is Ser-157, the preferred site for PKG/PRKG1, Ser-239. In ADP-activated platelets, phosphorylation by PKA or PKG on Ser-157 leads to fibrinogen receptor inhibition. Phosphorylation on Thr-278 requires prior phosphorylation on Ser-157 and Ser-239. In response to phorbol ester (PMA) stimulation, phosphorylated by PKC/PRKCA. In response to thrombin, phosphorylated by both PKC and ROCK1. Phosphorylation at Thr-278 by AMPK does not require prior phosphorylation at Ser-157 or Ser-239. Phosphorylation at Ser-157 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-322 by AMPK also alters actin filament binding. Carbon monoxide (CO) promotes phosphorylation at Ser-157, while nitric oxide (NO) promotes phosphorylation at Ser-157, but also at Ser-239. Response to NO and CO is blunted in platelets from diabetic patients, and VASP is not phosphorylated efficiently at Ser-157 and Ser-239.6 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP50552
MaxQBiP50552
PaxDbiP50552
PeptideAtlasiP50552
PRIDEiP50552
ProteomicsDBi56248
TopDownProteomicsiP50552

2D gel databases

OGPiP50552

PTM databases

iPTMnetiP50552
PhosphoSitePlusiP50552

Expressioni

Tissue specificityi

Highly expressed in platelets.1 Publication

Gene expression databases

BgeeiENSG00000125753
CleanExiHS_VASP
ExpressionAtlasiP50552 baseline and differential
GenevisibleiP50552 HS

Organism-specific databases

HPAiCAB004612
HPA005724

Interactioni

Subunit structurei

Homotetramer. 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 (By similarity). Interacts weakly with MEFV.By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin binding Source: UniProtKB-KW
  • cadherin binding Source: BHF-UCL
  • profilin binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW

Protein-protein interaction databases

BioGridi113251, 91 interactors
CORUMiP50552
DIPiDIP-44105N
ELMiP50552
IntActiP50552, 42 interactors
MINTiP50552
STRINGi9606.ENSP00000245932

Structurei

Secondary structure

1380
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 12Combined sources8
Beta strandi14 – 16Combined sources3
Turni18 – 20Combined sources3
Beta strandi25 – 27Combined sources3
Beta strandi34 – 41Combined sources8
Turni42 – 45Combined sources4
Beta strandi46 – 55Combined sources10
Beta strandi60 – 66Combined sources7
Beta strandi79 – 86Combined sources8
Beta strandi88 – 95Combined sources8
Helixi96 – 114Combined sources19
Helixi226 – 231Combined sources6
Helixi341 – 376Combined sources36

3D structure databases

ProteinModelPortaliP50552
SMRiP50552
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50552

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 113WH1PROSITE-ProRule annotationAdd BLAST112
Repeati344 – 3581Add BLAST15
Repeati359 – 3732Add BLAST15

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni225 – 377EVH2Add BLAST153
Regioni225 – 245EVH2 block AAdd BLAST21
Regioni259 – 278EVH2 block BAdd BLAST20
Regioni343 – 377EVH2 block CAdd BLAST35
Regioni344 – 3732 X 15 AA tandem repeats of L-[EQ]-[KR]-[MV]-K-[EQ]-E-[IL]-[IL]-E-[AEV]-[FV]-[KRV]-[KQ]-EAdd BLAST30

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili337 – 373Sequence analysisAdd BLAST37

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi234 – 237KLKR4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi118 – 216Pro-richAdd BLAST99
Compositional biasi215 – 222Poly-Gly8
Compositional biasi259 – 262Poly-Gly4
Compositional biasi322 – 325Poly-Ser4

Domaini

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.

Sequence similaritiesi

Belongs to the Ena/VASP family.Curated

Keywords - Domaini

Coiled coil, Repeat, SH3-binding

Phylogenomic databases

eggNOGiKOG4590 Eukaryota
ENOG41101TS LUCA
GeneTreeiENSGT00730000110272
HOGENOMiHOG000013015
HOVERGENiHBG006655
InParanoidiP50552
KOiK06274
OMAiMSETVIC
OrthoDBiEOG091G0QTE
PhylomeDBiP50552
TreeFamiTF321411

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR011993 PH-like_dom_sf
IPR034367 VASP
IPR017354 VASP/EVL
IPR038023 VASP_sf
IPR014885 VASP_tetra
IPR000697 WH1/EVH1_dom
PANTHERiPTHR11202:SF12 PTHR11202:SF12, 1 hit
PfamiView protein in Pfam
PF08776 VASP_tetra, 1 hit
PF00568 WH1, 1 hit
PIRSFiPIRSF038010 Vasodilator_Phospo, 1 hit
SMARTiView protein in SMART
SM00461 WH1, 1 hit
SUPFAMiSSF118370 SSF118370, 1 hit
PROSITEiView protein in PROSITE
PS50229 WH1, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P50552-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSETVICSSR ATVMLYDDGN KRWLPAGTGP QAFSRVQIYH NPTANSFRVV
60 70 80 90 100
GRKMQPDQQV VINCAIVRGV KYNQATPNFH QWRDARQVWG LNFGSKEDAA
110 120 130 140 150
QFAAGMASAL EALEGGGPPP PPALPTWSVP NGPSPEEVEQ QKRQQPGPSE
160 170 180 190 200
HIERRVSNAG GPPAPPAGGP PPPPGPPPPP GPPPPPGLPP SGVPAAAHGA
210 220 230 240 250
GGGPPPAPPL PAAQGPGGGG AGAPGLAAAI AGAKLRKVSK QEEASGGPTA
260 270 280 290 300
PKAESGRSGG GGLMEEMNAM LARRRKATQV GEKTPKDESA NQEEPEARVP
310 320 330 340 350
AQSESVRRPW EKNSTTLPRM KSSSSVTTSE TQPCTPSSSD YSDLQRVKQE
360 370 380
LLEEVKKELQ KVKEEIIEAF VQELRKRGSP
Length:380
Mass (Da):39,830
Last modified:January 23, 2007 - v3
Checksum:i17634B8134DEBF59
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2S → SS in AAH26019 (PubMed:15489334).Curated1
Sequence conflicti241Missing in AAH26019 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048929104A → T. Corresponds to variant dbSNP:rs10415373Ensembl.1
Natural variantiVAR_048930140Q → H. Corresponds to variant dbSNP:rs34345197Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46389 mRNA Translation: CAA86523.1
CH471126 Genomic DNA Translation: EAW57362.1
AK314812 mRNA Translation: BAG37336.1
BC026019 mRNA Translation: AAH26019.1
BC038224 mRNA Translation: AAH38224.1
X98534, X98533 Genomic DNA Translation: CAA67147.2
CCDSiCCDS33051.1
PIRiS51797
RefSeqiNP_003361.1, NM_003370.3
UniGeneiHs.515469

Genome annotation databases

EnsembliENST00000245932; ENSP00000245932; ENSG00000125753
GeneIDi7408
KEGGihsa:7408
UCSCiuc002pcg.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiVASP_HUMAN
AccessioniPrimary (citable) accession number: P50552
Secondary accession number(s): B2RBT9, Q6PIZ1, Q93035
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 185 of the entry and version 3 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, Direct protein sequencing, 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
  6. SIMILARITY comments
    Index of protein domains and families

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