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vasodilator-stimulated phosphoprotein (VASP, ENAH)
Function:
- actin-associated protein involved in a range of processes dependent on cytoskeleton remodeling & cell polarity including axon guidance & lamellipodial & filopodial dynamics in migrating cells
- promotes actin nucleation & increases the rate of actin polymerization in the presence of capping protein
- associated with actin/integrin focal contacts
- major substrate for cAMP-dependent protein kinase (PKA) & cGMP-dependent protein kinase (PKG) in platelets
- preferred site for PKA is Ser-157
- preferred site for PKG, 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 & Ser-239
- in response to phorbol ester (PMA) stimulation, phosphorylated by PKC/PRKCA
- in response to thrombin, phosphorylated by both PKC & ROCK1
- interacts with PFN1, PFN2, LPP, ACTN1 & ACTG1
- interacts, via the EVH1, with the Pro-rich regions of ZYX; this interaction is important for targeting to focal adhesions & formation of actin-rich structures at the apical surface of cells
- interacts with APBB1IP
- interacts, via Pro-rich domain, with C-terminal SH3 domain of DNMBP
Structure:
- homotetramer
- 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 & for actin polymerization
- block B is required for F-actin binding & subcellular location, & block C for tetramerization
- the WH1 domain mediates interaction with XIRP1
- belongs to the Ena/VASP family
- contains 1 WH1 domain
Compartment:
- cytoplasm, cytoskeleton
- cell junction, focal adhesion
- cell projection, lamellipodium membrane
- cell projection, filopodium membrane
- targeted to stress fibers & focal adhesions through interaction with a number of proteins including MRL family members
- localizes to the plasma membrane in protruding lamellipodia & filopodial tips
- stimulation by thrombin or PMA, also translocates VASP to focal adhesions
Expression: highly expressed in platelets
Pathology:
- role in actin-based activity of Listeria monocytogenes in platelets (putative)
- VASP interacts, via EVH1 domain, with the Pro-rich domain of Listeria monocytogenes actA
General
cytoskeletal protein
phosphoprotein
Properties
SIZE: entity length = 380 aa
MW = 40 kD
COMPARTMENT: cytoplasm
MOTIF: WH1 {2-113}
acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
Tyr phosphorylation site {Y39}
proline-rich region
SITE: 118-216
MOTIF: proline residue (SEVERAL)
Ser phosphorylation site {S157}
glycine-rich region {215-222}
EVH2 {225-377}
MOTIF: EVH2 block A {225-245}
KLKR {234-237}
Ser phosphorylation site {S239}
EVH2 block B {259-278}
glycine-rich region {259-262}
Thr phosphorylation site {T278}
Thr phosphorylation site {T316}
serine-rich region {322-325}
MOTIF: serine residue (SEVERAL)
Ser phosphorylation site {S322}
Ser phosphorylation site {S323}
coiled coil {337-373}
EVH2 block C {343-377}
repeats {344-373}
consensus repeat {344-358}
consensus repeat {359-373}
Database Correlations
OMIM 601703
UniProt P50552
PFAM correlations
Entrez Gene 7408
Kegg hsa:7408
References
- Stossel TP.
On the crawling of animal cells.
Science. 1993 May 21;260(5111):1086-94. Review.
PMID: 8493552
- UniProt :accession P50552