Vasodilator-stimulated phosphoprotein

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Reviewed, UniProtKB/Swiss-Prot P50552 (VASP_HUMAN)

Last modified November 25, 2008. Version 89. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
Vasodilator-stimulated phosphoprotein
Short name=VASP

Gene names

Name:

VASP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	380 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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 and lamellipodial and filopodial dynamics in migrating cells. VASP promotes actin nucleation and increases the rate of actin polymerization in the presence of capping protein. Plays a role in actin-based activity of Listeria monocytogenes in platelets By similarity.
Subunit structure	Homotetramer. Interacts with PFN1, PFN2, LPP, ACTN1 and ACTG1. Interacts, via the EVH1, 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.
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton. Cell junction › focal adhesion. Cell projection › lamellipodium membrane. Cell projection › filopodium 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.
Tissue specificity	Highly expressed in platelets.
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.
Post-translational modification	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, 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.
Sequence similarities	Belongs to the Ena/VASP family. Contains 1 WH1 domain.

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Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane
Domain	Coiled coil Repeat SH3-binding
Ligand	Actin-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Cellular component	actin cytoskeleton Ref.1 Traceable author statement. Source: ProtInc cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW focal adhesion Inferred from direct assay. Source: HPA
Molecular function	SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW actin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed

Chain

2 – 380

379

Vasodilator-stimulated phosphoprotein

PRO_0000065767

Regions

Domain

2 – 113

112

WH1

Repeat

344 – 358

Repeat

359 – 373

Region

225 – 377

153

EVH2

Region

225 – 245

EVH2 block A

Region

259 – 278

EVH2 block B

Region

343 – 377

EVH2 block C

Region

344 – 373

2 X 15 AA tandem repeats of L-[EQ]-[KR]-[MV]-K-[EQ]-E-[IL]-[IL]-E-[AEV]-[FV]-[KRV]-[KQ]-E

Coiled coil

337 – 373

Potential

Motif

234 – 237

KLKR

Compositional bias

118 – 216

Pro-rich

Compositional bias

215 – 222

Poly-Gly

Compositional bias

259 – 262

Poly-Gly

Compositional bias

322 – 325

Poly-Ser

Amino acid modifications

Modified residue

N-acetylserine

Modified residue

Phosphotyrosine

Modified residue

157

Phosphoserine; by PKA, PKC, PKG and ROCK1

Modified residue

239

Phosphoserine; by PKA and PKG

Modified residue

278

Phosphothreonine; by PKA and PKG

Modified residue

316

Phosphothreonine

Modified residue

322

Phosphoserine

Modified residue

323

Phosphoserine By similarity

Experimental info

Mutagenesis

370

F → A: Lower stability of tetramerization domain

Mutagenesis

370

F → I or K: No change in stability of tetramerization domain

Sequence conflict

S → SS in AAH26019. Ref.3

Sequence conflict

241

Missing in AAH26019. Ref.3

Secondary structure

380

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P50552-1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 17634B8134DEBF59
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FASTA

380

39,830

        10         20         30         40         50         60 
MSETVICSSR ATVMLYDDGN KRWLPAGTGP QAFSRVQIYH NPTANSFRVV GRKMQPDQQV 

        70         80         90        100        110        120 
VINCAIVRGV KYNQATPNFH QWRDARQVWG LNFGSKEDAA QFAAGMASAL EALEGGGPPP 

       130        140        150        160        170        180 
PPALPTWSVP NGPSPEEVEQ QKRQQPGPSE HIERRVSNAG GPPAPPAGGP PPPPGPPPPP 

       190        200        210        220        230        240 
GPPPPPGLPP SGVPAAAHGA GGGPPPAPPL PAAQGPGGGG AGAPGLAAAI AGAKLRKVSK 

       250        260        270        280        290        300 
QEEASGGPTA PKAESGRSGG GGLMEEMNAM LARRRKATQV GEKTPKDESA NQEEPEARVP 

       310        320        330        340        350        360 
AQSESVRRPW EKNSTTLPRM KSSSSVTTSE TQPCTPSSSD YSDLQRVKQE LLEEVKKELQ 

       370        380 
KVKEEIIEAF VQELRKRGSP

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, structural analysis and functional expression of the proline-rich focal adhesion and microfilament-associated protein VASP." Haffner C., Jarchau T., Reinhard M., Hoppe J., Lohmann S.M., Walter U. EMBO J. 14:19-27(1995) [PubMed: 7828592] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 11-32; 87-96; 140-154; 255-282 AND 297-322, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, POSSIBLE FUNCTION. Tissue: Promyelocyte.
[2]	"Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes." Laurent V., Loisel T.P., Harbeck B., Wehman A., Groebe L., Jockusch B.M., Wehland J., Gertler F.B., Carlier M.-F. J. Cell Biol. 144:1245-1258(1999) [PubMed: 10087267] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH L.MONOCYTOGENES ACTA.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Fetal lung, Fetal spleen and Skin.
[4]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-10, ACETYLATION AT SER-2. Tissue: Platelet.
[5]	"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: 8812448] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3-380.
[6]	"cAMP- and cGMP-dependent protein kinase phosphorylation sites of the focal adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro and in intact human platelets." Butt E., Abel K., Krieger M., Palm D., Hoppe V., Hoppe J., Walter U. J. Biol. Chem. 269:14509-14517(1994) [PubMed: 8182057] [Abstract] Cited for: PROTEIN SEQUENCE OF 143-164; 235-244 AND 267-285, PHOSPHORYLATION AT SER-157; SER-239 AND THR-278.
[7]	"Phosphorylation of focal adhesion vasodilator-stimulated phosphoprotein at Ser157 in intact human platelets correlates with fibrinogen receptor inhibition." Horstrup K., Jablonka B., Honig-Liedl P., Just M., Kochsiek K., Walter U. Eur. J. Biochem. 225:21-27(1994) [PubMed: 7925440] [Abstract] Cited for: PHOSPHORYLATION AT SER-157, FIBRINOGEN RECEPTOR INHIBITION.
[8]	"The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins." Reinhard M., Giehl K., Abel K., Haffner C., Jarchau T., Hoppe V., Jockusch B.M., Walter U. EMBO J. 14:1583-1589(1995) [PubMed: 7737110] [Abstract] Cited for: INTERACTION WITH ACTG1 AND PFN1.
[9]	"The EVH2 domain of the vasodilator-stimulated phosphoprotein mediates tetramerization, F-actin binding, and actin bundle formation." Bachmann C., Fischer L., Walter U., Reinhard M. J. Biol. Chem. 274:23549-23557(1999) [PubMed: 10438535] [Abstract] Cited for: FUNCTION OF EVH2 DOMAIN.
[10]	"Characterization of the interaction between zyxin and members of the Ena/vasodilator-stimulated phosphoprotein family of proteins." Drees B., Friederich E., Fradelizi J., Louvard D., Beckerle M.C., Golsteyn R.M. J. Biol. Chem. 275:22503-22511(2000) [PubMed: 10801818] [Abstract] Cited for: INTERACTION WITH ZYX.
[11]	"LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity." Petit M.M., Fradelizi J., Golsteyn R.M., Ayoubi T.A., Menichi B., Louvard D., Van de Ven W.J.M., Friederich E. Mol. Biol. Cell 11:117-129(2000) [PubMed: 10637295] [Abstract] Cited for: INTERACTION WITH LPP.
[12]	"Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics." Krause M., Leslie J.D., Stewart M., Lafuente E.M., Valderrama F., Jagannathan R., Strasser G.A., Rubinson D.A., Liu H., Way M., Yaffe M.B., Boussiotis V.A., Gertler F.B. Dev. Cell 7:571-583(2004) [PubMed: 15469845] [Abstract] Cited for: INTERACTION WITH RAPH1.
[13]	"Vasodilator-stimulated phosphoprotein is a substrate for protein kinase C." Chitaley K., Chen L., Galler A., Walter U., Daum G., Clowes A.W. FEBS Lett. 556:211-215(2004) [PubMed: 14706852] [Abstract] Cited for: PHOSPHORYLATION BY PKC.
[14]	"Ena/VASP proteins enhance actin polymerization in the presence of barbed end capping proteins." Barzik M., Kotova T.I., Higgs H.N., Hazelwood L., Hanein D., Gertler F.B., Schafer D.A. J. Biol. Chem. 280:28653-28662(2005) [PubMed: 15939738] [Abstract] Cited for: FUNCTION.
[15]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39, MASS SPECTROMETRY.
[16]	"Vasodilator-stimulated phosphoprotein (VASP) is phosphorylated on Ser 157 by protein kinase C-dependent and -independent mechanisms in thrombin-stimulated human platelets." Wentworth J.K., Pula G., Poole A.W. Biochem. J. 393:555-564(2006) [PubMed: 16197368] [Abstract] Cited for: PHOSPHORYLATION AT SER-157, SUBCELLULAR LOCATION.
[17]	"Unusual splicing events result in distinct Xin isoforms that associate differentially with filamin c and Mena/VASP." van der Ven P.F.M., Ehler E., Vakeel P., Eulitz S., Schenk J.A., Milting H., Micheel B., Fuerst D.O. Exp. Cell Res. 312:2154-2167(2006) [PubMed: 16631741] [Abstract] Cited for: INTERACTION WITH XIRP1.
[18]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39, MASS SPECTROMETRY.
[19]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, MASS SPECTROMETRY.
[20]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-316 AND SER-322, MASS SPECTROMETRY.
[21]	"The VASP tetramerization domain is a right-handed coiled coil based on a 15-residue repeat." Kuehnel K., Jarchau T., Wolf E., Schlichting I., Walter U., Wittinghofer A., Strelkov S.V. Proc. Natl. Acad. Sci. U.S.A. 101:17027-17032(2004) [PubMed: 15569942] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 336-380, TETRAMERIZATION, MUTAGENESIS OF PHE-370.
[22]	"Dual epitope recognition by the VASP EVH1 domain modulates polyproline ligand specificity and binding affinity." Ball L.J., Kuehne R., Hoffmann B., Haefner A., Schmieder P., Volkmer-Engert R., Hof M., Wahl M., Schneider-Mergener J., Walter U., Oschkinat H., Jarchau T. EMBO J. 19:4903-4914(2000) [PubMed: 10990454] [Abstract] Cited for: STRUCTURE BY NMR OF 1-115.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

Z46389 mRNA. Translation: CAA86523.1.
BC026019 mRNA. Translation: AAH26019.1.
BC038224 mRNA. Translation: AAH38224.1.
X98534, X98533 Genomic DNA. Translation: CAA67147.2.

PIR

S51797.

RefSeq

NP_003361.1.

UniGene

Hs.702197

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EGX	NMR	-	A	1-115	[»]
1JNG	model	-	A	1-115	[»]
1USD	X-ray	1.70	A	336-380	[»]
1USE	X-ray	1.30	A	336-380	[»]
2PAV	X-ray	1.80	V	199-214	[»]
2PBD	X-ray	1.50	V	203-245	[»]