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Protein

Vasodilator-stimulated phosphoprotein

Gene

VASP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • profilin binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

Actin-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000125753-MONOMER.
ReactomeiR-HSA-202433. Generation of second messenger molecules.
R-HSA-376176. Signaling by Robo receptor.
R-HSA-446353. Cell-extracellular matrix interactions.
SIGNORiP50552.

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

HGNCiHGNC:12652. VASP.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: ProtInc
  • bicellular tight junction Source: UniProtKB-SubCell
  • cell-cell adherens junction Source: BHF-UCL
  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • filopodium membrane Source: UniProtKB-SubCell
  • focal adhesion Source: UniProtKB
  • lamellipodium membrane Source: UniProtKB-SubCell
  • plasma membrane Source: HPA
Complete GO annotation...

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.

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

WithEntry#Exp.IntActNotes
ABI2Q9NYB93EBI-748201,EBI-743598
ABI3Q9P2A45EBI-748201,EBI-742038
BAIAP2Q9UQB8-46EBI-748201,EBI-6174091
FGFR1OPO956843EBI-748201,EBI-1266334
NR4A1P227362EBI-748201,EBI-721550
NSMAFQ926362EBI-748201,EBI-2947053
RPS6KA1Q154184EBI-748201,EBI-963034
SCGB2A2Q132963EBI-748201,EBI-9058786
TRIM9Q9C0263EBI-748201,EBI-720828
VCLP120032EBI-748201,EBI-1039563From a different organism.
XIRP1Q702N85EBI-748201,EBI-7851194

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • profilin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113251. 79 interactors.
DIPiDIP-44105N.
IntActiP50552. 35 interactors.
MINTiMINT-1437861.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EGXNMR-A1-115[»]
1JNGmodel-A1-115[»]
1USDX-ray1.70A336-380[»]
1USEX-ray1.30A336-380[»]
2PAVX-ray1.80V199-214[»]
2PBDX-ray1.50V203-245[»]
3CHWX-ray2.30V199-214[»]
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
Contains 1 WH1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat, SH3-binding

Phylogenomic databases

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

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR017354. Vasodilator_phosphoprotein.
IPR014885. VASP_tetra.
IPR000697. WH1/EVH1_dom.
[Graphical view]
PANTHERiPTHR11202:SF12. PTHR11202:SF12. 1 hit.
PfamiPF08776. VASP_tetra. 1 hit.
PF00568. WH1. 1 hit.
[Graphical view]
PIRSFiPIRSF038010. Vasodilator_Phospo. 1 hit.
SMARTiSM00461. WH1. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS50229. WH1. 1 hit.
[Graphical view]

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 rs10415373dbSNPEnsembl.1
Natural variantiVAR_048930140Q → H.Corresponds to variant rs34345197dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EGXNMR-A1-115[»]
1JNGmodel-A1-115[»]
1USDX-ray1.70A336-380[»]
1USEX-ray1.30A336-380[»]
2PAVX-ray1.80V199-214[»]
2PBDX-ray1.50V203-245[»]
3CHWX-ray2.30V199-214[»]
ProteinModelPortaliP50552.
SMRiP50552.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113251. 79 interactors.
DIPiDIP-44105N.
IntActiP50552. 35 interactors.
MINTiMINT-1437861.
STRINGi9606.ENSP00000245932.

PTM databases

iPTMnetiP50552.
PhosphoSitePlusiP50552.

Polymorphism and mutation databases

BioMutaiVASP.
DMDMi1718079.

2D gel databases

OGPiP50552.

Proteomic databases

EPDiP50552.
MaxQBiP50552.
PaxDbiP50552.
PeptideAtlasiP50552.
PRIDEiP50552.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7408.
DisGeNETi7408.
GeneCardsiVASP.
HGNCiHGNC:12652. VASP.
HPAiCAB004612.
HPA005724.
MIMi601703. gene.
neXtProtiNX_P50552.
OpenTargetsiENSG00000125753.
PharmGKBiPA37276.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000125753-MONOMER.
ReactomeiR-HSA-202433. Generation of second messenger molecules.
R-HSA-376176. Signaling by Robo receptor.
R-HSA-446353. Cell-extracellular matrix interactions.
SIGNORiP50552.

Miscellaneous databases

ChiTaRSiVASP. human.
EvolutionaryTraceiP50552.
GeneWikiiVasodilator-stimulated_phosphoprotein.
GenomeRNAii7408.
PROiP50552.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125753.
CleanExiHS_VASP.
ExpressionAtlasiP50552. baseline and differential.
GenevisibleiP50552. HS.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR017354. Vasodilator_phosphoprotein.
IPR014885. VASP_tetra.
IPR000697. WH1/EVH1_dom.
[Graphical view]
PANTHERiPTHR11202:SF12. PTHR11202:SF12. 1 hit.
PfamiPF08776. VASP_tetra. 1 hit.
PF00568. WH1. 1 hit.
[Graphical view]
PIRSFiPIRSF038010. Vasodilator_Phospo. 1 hit.
SMARTiSM00461. WH1. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS50229. WH1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVASP_HUMAN
AccessioniPrimary (citable) accession number: P50552
Secondary accession number(s): B2RBT9, Q6PIZ1, Q93035
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 170 of the entry and version 3 of the sequence. [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

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.

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.