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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

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi157 – 1571S → 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 Publication
Mutagenesisi239 – 2391S → 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 Publication
Mutagenesisi278 – 2781T → A: Promotes F-actin assembly; when associated with A-157 and A-239. 1 Publication
Mutagenesisi278 – 2781T → E: Interferes with F-actin assembly; when associated with A-157 and A-239. 1 Publication
Mutagenesisi370 – 3701F → A: Lower stability of tetramerization domain. 1 Publication
Mutagenesisi370 – 3701F → I or K: No change in stability of tetramerization domain. 1 Publication

Organism-specific databases

PharmGKBiPA37276.

Polymorphism and mutation databases

BioMutaiVASP.
DMDMi1718079.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources1 Publication
Chaini2 – 380379Vasodilator-stimulated phosphoproteinPRO_0000065767Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineCombined sources1 Publication
Modified residuei39 – 391PhosphotyrosineCombined sources
Modified residuei46 – 461PhosphoserineCombined sources
Modified residuei157 – 1571Phosphoserine; by PKA, PKC, PKG/PRKG1 and ROCK14 Publications
Modified residuei239 – 2391Phosphoserine; by PKA and PKG/PRKG1Combined sources2 Publications
Modified residuei278 – 2781Phosphothreonine; by PKA, PKG/PRKG1 and AMPK2 Publications
Modified residuei283 – 2831N6-acetyllysineCombined sources
Modified residuei284 – 2841PhosphothreonineCombined sources
Modified residuei305 – 3051PhosphoserineCombined sources
Modified residuei314 – 3141PhosphoserineCombined sources
Modified residuei316 – 3161PhosphothreonineCombined sources
Modified residuei322 – 3221Phosphoserine; by AMPKCombined sources
Modified residuei323 – 3231PhosphoserineBy similarity
Modified residuei325 – 3251PhosphoserineBy similarity

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.
PhosphoSiteiP50552.

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
ABI3Q9P2A43EBI-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
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 interactions.
DIPiDIP-44105N.
IntActiP50552. 33 interactions.
MINTiMINT-1437861.
STRINGi9606.ENSP00000245932.

Structurei

Secondary structure

1
380
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi5 – 128Combined sources
Beta strandi14 – 163Combined sources
Turni18 – 203Combined sources
Beta strandi25 – 273Combined sources
Beta strandi34 – 418Combined sources
Turni42 – 454Combined sources
Beta strandi46 – 5510Combined sources
Beta strandi60 – 667Combined sources
Beta strandi79 – 868Combined sources
Beta strandi88 – 958Combined sources
Helixi96 – 11419Combined sources
Helixi226 – 2316Combined sources
Helixi341 – 37636Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 1-115, 338-377.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50552.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 113112WH1PROSITE-ProRule annotationAdd
BLAST
Repeati344 – 358151Add
BLAST
Repeati359 – 373152Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni225 – 377153EVH2Add
BLAST
Regioni225 – 24521EVH2 block AAdd
BLAST
Regioni259 – 27820EVH2 block BAdd
BLAST
Regioni343 – 37735EVH2 block CAdd
BLAST
Regioni344 – 373302 X 15 AA tandem repeats of L-[EQ]-[KR]-[MV]-K-[EQ]-E-[IL]-[IL]-E-[AEV]-[FV]-[KRV]-[KQ]-EAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili337 – 37337Sequence analysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi234 – 2374KLKR

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi118 – 21699Pro-richAdd
BLAST
Compositional biasi215 – 2228Poly-Gly
Compositional biasi259 – 2624Poly-Gly
Compositional biasi322 – 3254Poly-Ser

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti2 – 21S → SS in AAH26019 (PubMed:15489334).Curated
Sequence conflicti241 – 2411Missing in AAH26019 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti104 – 1041A → T.
Corresponds to variant rs10415373 [ dbSNP | Ensembl ].
VAR_048929
Natural varianti140 – 1401Q → H.
Corresponds to variant rs34345197 [ dbSNP | Ensembl ].
VAR_048930

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
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. Positions 1-115, 338-377.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113251. 79 interactions.
DIPiDIP-44105N.
IntActiP50552. 33 interactions.
MINTiMINT-1437861.
STRINGi9606.ENSP00000245932.

PTM databases

iPTMnetiP50552.
PhosphoSiteiP50552.

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

Phylogenomic databases

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

Enzyme and pathway databases

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: September 7, 2016
This is version 167 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.