P70460 (VASP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vasodilator-stimulated phosphoprotein
Short name=VASP

Gene names

Name:

Vasp

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	375 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

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, 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 By similarity. Ref.6
Subunit structure	Homotetramer By similarity. 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. Ref.7 Ref.8 Ref.9 Ref.10
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. Ref.6
Tissue specificity	Highly expressed in thymus and spleen. Lower levels in lung, ovary, placenta and fat. Ref.5
Developmental stage	Expressed constantly throughout brain development, with lower levels in adulthood. Ref.5
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 By similarity.
Post-translational modification	Major substrate for cAMP-dependent (PKA) and cGMP-dependent protein kinase (PKG) in platelets. The preferred site for PKA is Ser-153, the preferred site for PKG, Ser-235. In ADP-activated platelets, phosphorylation by PKA or PKG/PRKG1 on Ser-153 leads to fibrinogen receptor inhibition. Phosphorylation on Thr-274 requires prior phosphorylation on Ser-153 and Ser-235. In response to phorbol ester (PMA) stimulation, phosphorylated by PKC/PRKCA. In response to thrombin, phosphorylated by both PKC and ROCK1. Phosphorylation at Thr-274 by AMPK does not require prior phosphorylation at Ser-153 or Ser-235. Phosphorylation modulates F-actin binding, actin filament elongation and platelet activation. Phosphorylation at Ser-318 by AMPK also alters actin filament binding. Carbon monoxide (CO) promotes phosphorylation at Ser-153, while nitric oxide (NO) promotes phosphorylation at Ser-153, but also at Ser-235. Ref.2 Ref.7 Ref.8 Ref.12
Sequence similarities	Belongs to the Ena/VASP family. Contains 1 WH1 domain.
Sequence caution	The sequence CAA67108.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Polymorphism
Domain	Coiled coil Repeat SH3-binding
Ligand	Actin-binding
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Inferred from genetic interaction PubMed 15371503. Source: MGI actin polymerization or depolymerization Inferred from electronic annotation. Source: InterPro axon guidance Inferred from genetic interaction PubMed 15371503. Source: MGI neural tube closure Inferred from genetic interaction PubMed 15371503. Source: MGI protein homotetramerization Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome filopodium Inferred from direct assay PubMed 15148305PubMed 15294161. Source: MGI filopodium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell focal adhesion Inferred from direct assay PubMed 15148305. Source: MGI lamellipodium Inferred from direct assay PubMed 15148305. Source: MGI lamellipodium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 375	374	Vasodilator-stimulated phosphoprotein		PRO_0000065768
Regions
	Domain	2 – 113	112	WH1
	Repeat	340 – 354	15	1
	Repeat	355 – 369	15	2
	Region	221 – 373	153	EVH2
	Region	221 – 241	21	EVH2 block A
	Region	257 – 274	18	EVH2 block B
	Region	338 – 372	35	EVH2 block C
	Region	339 – 368	30	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 – 367	31	Potential
	Motif	230 – 233	4	KLKR
	Compositional bias	166 – 182	17	Poly-Pro
	Compositional bias	317 – 320	4	Poly-Ser
Amino acid modifications
	Modified residue	2	1	N-acetylserine By similarity
	Modified residue	39	1	Phosphotyrosine By similarity
	Modified residue	153	1	Phosphoserine; by PKA, PKC, PKG/PRKG1 and ROCK1
	Modified residue	235	1	Phosphoserine; by PKA and PKG
	Modified residue	274	1	Phosphothreonine; by PKA, PKG/PRKG1 and AMPK By similarity
	Modified residue	279	1	N6-acetyllysine By similarity
	Modified residue	311	1	Phosphothreonine By similarity
	Modified residue	317	1	Phosphoserine Ref.11
	Modified residue	318	1	Phosphoserine; by AMPK Ref.11 Ref.12
Natural variations
	Natural variant	209	1	A → T. Ref.1 Ref.3
Experimental info
	Mutagenesis	153	1	S → D: Reduces actin polymerization to a lesser extent than wild-type. Greater effect on actin polymerization; when associated with D-235 and E-274. Ref.7 Ref.8
	Mutagenesis	232 – 233	2	RK → GE or EE: Reduced binding to monomeric actin. No VASP-induced actin polymerization. Ref.8
	Mutagenesis	235	1	S → D: Reduces actin polymerization to a lesser extent than wild-type. Ref.7 Ref.8
	Mutagenesis	274	1	T → E: Reduces actin polymerization to a lesser extent than wild-type. Ref.7 Ref.8
	Sequence conflict	106 – 115	10	Missing in BAE42025. Ref.3
	Sequence conflict	237	1	Missing in BAE33933. Ref.3
	Sequence conflict	337	1	S → Y in BAE29310. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P70460 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 19369286CF4276C7	FASTA	375	39,667
	10 20 30 40 50 60 MSETVICSSR ATVMLYDDSN KRWLPAGTGP QAFSRVQIYH NPTANSFRVV GRKMQPDQQV 70 80 90 100 110 120 VINCAIIRGV KYNQATPIFH QWRDARQVWG LNFGSKEDAI QFATGMANAL EALEGGGPPP 130 140 150 160 170 180 APAPPAWSAQ NGPSPEELEQ QKRQPEHMER RVSNAGGPPA PPAGGPPPPP GPPPPPGPPP 190 200 210 220 230 240 PPGLPSSGVS GAGHGAGAAP PPAPPLPTAQ GPNSGGSGAP GLAAAIAGAK LRKVSKQEEA 250 260 270 280 290 300 SGGPLAPKAE NSRSTGGGLM EEMNAMLARR RKATQVGEKP PKDESASEES EARLPAQSEP 310 320 330 340 350 360 VRRPWEKNST TLPRMKSSSS VTTSEAHPST PCSSDDSDLE RVKQELLEEV RKELQKMKEE 370 IIEVFVQELR KRGSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-209. Strain: 129.
[2]	"Cyclic AMP- and cyclic GMP-dependent protein kinases differ in their regulation of cyclic AMP response element-dependent gene transcription." Collins S.P., Uhler M.D. J. Biol. Chem. 274:8391-8404(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION. Strain: C57BL/6J.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-209. Strain: C57BL/6J and NOD. Tissue: Adipose tissue, Bone marrow, Dendritic cell and Spleen.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Kidney and Mammary tumor.
[5]	"Mena is required for neurulation and commissure formation." Lanier L.M., Gates M.A., Witke W., Menzies A.S., Wehman A.M., Macklis J.D., Kwiatkowski D., Soriano P., Gertler F.B. Neuron 22:313-325(1999) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
[6]	"Directed actin polymerization is the driving force for epithelial cell-cell adhesion." Vasioukhin V., Bauer C., Yin M., Fuchs E. Cell 100:209-219(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]	"Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its interaction with actin." Harbeck B., Huttelmaier S., Schlueter K., Jockusch B.M., Illenberger S. J. Biol. Chem. 275:30817-30825(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ACTN1; PFN1; PFN2; VCL AND ZYX, PHOSPHORYLATION, MUTAGENESIS OF SER-153; SER-235 AND THR-274.
[8]	"The vasodilator-stimulated phosphoprotein promotes actin polymerisation through direct binding to monomeric actin." Walders-Harbeck B., Khaitlina S.Y., Hinssen H., Jockusch B.M., Illenberger S. FEBS Lett. 529:275-280(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ACTG1, PHOSPHORYLATION, MUTAGENESIS OF 232-ARG-LYS-233.
[9]	"Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology domains, links dynamin to regulation of the actin cytoskeleton." Salazar M.A., Kwiatkowski A.V., Pellegrini L., Cestra G., Butler M.H., Rossman K.L., Serna D.M., Sondek J., Gertler F.B., De Camilli P. J. Biol. Chem. 278:49031-49043(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DNMBP.
[10]	"PREL1 provides a link from Ras signalling to the actin cytoskeleton via Ena/VASP proteins." Jenzora A., Behrendt B., Small J.V., Wehland J., Stradal T.E. FEBS Lett. 579:455-463(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APBB1IP.
[11]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-317 AND SER-318, MASS SPECTROMETRY. Tissue: Liver.
[12]	"Phosphorylation of VASP by AMPK alters actin binding and occurs at a novel site." Thomson D.M., Ascione M.P., Grange J., Nelson C., Hansen M.D. Biochem. Biophys. Res. Commun. 414:215-219(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-318.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X98475 Genomic DNA. Translation: CAA67108.1. Sequence problems. AF084548 mRNA. Translation: AAD16045.1. AK140329 mRNA. Translation: BAE24338.1. AK150103 mRNA. Translation: BAE29310.1. AK157021 mRNA. Translation: BAE33933.1. AK170780 mRNA. Translation: BAE42025.1. AK171715 mRNA. Translation: BAE42628.1. BC010223 mRNA. Translation: AAH10223.1. BC015289 mRNA. Translation: AAH15289.1.
IPI	IPI00624876.
RefSeq	NP_033525.2. NM_009499.2.
UniGene	Mm.9684.
3D structure databases
ProteinModelPortal	P70460.
SMR	P70460. Positions 1-115, 333-372.
ModBase	Search...
Protein-protein interaction databases
IntAct	P70460. 1 interaction.
MINT	MINT-1215713.
PTM databases
PhosphoSite	P70460.
Proteomic databases
PaxDb	P70460.
PRIDE	P70460.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000032561; ENSMUSP00000032561; ENSMUSG00000030403.
GeneID	22323.
KEGG	mmu:22323.
UCSC	uc009fle.2. mouse.
Organism-specific databases
CTD	7408.
MGI	MGI:109268. Vasp.
Phylogenomic databases
eggNOG	NOG265043.
GeneTree	ENSGT00440000039080.
HOVERGEN	HBG006655.
InParanoid	P70460.
KO	K06274.
OMA	PTWSVPN.
OrthoDB	EOG49GKHQ.
Enzyme and pathway databases
Reactome	REACT_107772. Immune System.
Gene expression databases
Bgee	P70460.
CleanEx	MM_VASP.
Genevestigator	P70460.
GermOnline	ENSMUSG00000030403. Mus musculus.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR000697. EVH1. IPR011993. PH_like_dom. IPR017354. Vasodilator_phosphoprotein. IPR014885. VASP_tetra. [Graphical view]
Pfam	PF08776. VASP_tetra. 1 hit. PF00568. WH1. 1 hit. [Graphical view]
PIRSF	PIRSF038010. Vasodilator_Phospo. 1 hit.
SMART	SM00461. WH1. 1 hit. [Graphical view]
PROSITE	PS50229. WH1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	VASP. mouse.
NextBio	302545.
SOURCE	Search...

Entry information

Entry name

VASP_MOUSE

Accession

Primary (citable) accession number: P70460
Secondary accession number(s): Q3TAP0 , Q3TCD2, Q3U0C2, Q3UDF1, Q91VD2, Q9R214

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 111 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program