Full text data of VASP
VASP
[Confidence: high (present in two of the MS resources)]
Vasodilator-stimulated phosphoprotein; VASP
Vasodilator-stimulated phosphoprotein; VASP
UniProt
P50552
ID VASP_HUMAN Reviewed; 380 AA.
AC P50552; B2RBT9; Q6PIZ1; Q93035;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Vasodilator-stimulated phosphoprotein;
DE Short=VASP;
GN Name=VASP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 11-32; 87-96; 140-154;
RP 255-282 AND 297-322, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP POSSIBLE FUNCTION.
RC TISSUE=Promyelocyte;
RX PubMed=7828592;
RA Haffner C., Jarchau T., Reinhard M., Hoppe J., Lohmann S.M.,
RA Walter U.;
RT "Molecular cloning, structural analysis and functional expression of
RT the proline-rich focal adhesion and microfilament-associated protein
RT VASP.";
RL EMBO J. 14:19-27(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH
RP L.MONOCYTOGENES ACTA.
RX PubMed=10087267; DOI=10.1083/jcb.144.6.1245;
RA Laurent V., Loisel T.P., Harbeck B., Wehman A., Groebe L.,
RA Jockusch B.M., Wehland J., Gertler F.B., Carlier M.-F.;
RT "Role of proteins of the Ena/VASP family in actin-based motility of
RT Listeria monocytogenes.";
RL J. Cell Biol. 144:1245-1258(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Substantia nigra;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal lung, Fetal spleen, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 2-10, AND ACETYLATION AT SER-2.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3-380.
RX PubMed=8812448; DOI=10.1006/geno.1996.0457;
RA Zimmer M., Fink T., Fischer L., Hauser W., Scherer K., Lichter P.,
RA Walter U.;
RT "Cloning of the VASP (vasodilator-stimulated phosphoprotein) genes in
RT human and mouse: structure, sequence, and chromosomal localization.";
RL Genomics 36:227-233(1996).
RN [8]
RP PROTEIN SEQUENCE OF 143-164; 235-244 AND 267-285, AND PHOSPHORYLATION
RP AT SER-157; SER-239 AND THR-278 BY PRKG1.
RX PubMed=8182057;
RA Butt E., Abel K., Krieger M., Palm D., Hoppe V., Hoppe J., Walter U.;
RT "cAMP- and cGMP-dependent protein kinase phosphorylation sites of the
RT focal adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro
RT and in intact human platelets.";
RL J. Biol. Chem. 269:14509-14517(1994).
RN [9]
RP PHOSPHORYLATION AT SER-157, AND FIBRINOGEN RECEPTOR INHIBITION.
RX PubMed=7925440; DOI=10.1111/j.1432-1033.1994.00021.x;
RA Horstrup K., Jablonka B., Honig-Liedl P., Just M., Kochsiek K.,
RA Walter U.;
RT "Phosphorylation of focal adhesion vasodilator-stimulated
RT phosphoprotein at Ser157 in intact human platelets correlates with
RT fibrinogen receptor inhibition.";
RL Eur. J. Biochem. 225:21-27(1994).
RN [10]
RP INTERACTION WITH ACTG1 AND PFN1.
RX PubMed=7737110;
RA Reinhard M., Giehl K., Abel K., Haffner C., Jarchau T., Hoppe V.,
RA Jockusch B.M., Walter U.;
RT "The proline-rich focal adhesion and microfilament protein VASP is a
RT ligand for profilins.";
RL EMBO J. 14:1583-1589(1995).
RN [11]
RP FUNCTION OF EVH2 DOMAIN.
RX PubMed=10438535; DOI=10.1074/jbc.274.33.23549;
RA Bachmann C., Fischer L., Walter U., Reinhard M.;
RT "The EVH2 domain of the vasodilator-stimulated phosphoprotein mediates
RT tetramerization, F-actin binding, and actin bundle formation.";
RL J. Biol. Chem. 274:23549-23557(1999).
RN [12]
RP INTERACTION WITH ZYX.
RX PubMed=10801818; DOI=10.1074/jbc.M001698200;
RA Drees B., Friederich E., Fradelizi J., Louvard D., Beckerle M.C.,
RA Golsteyn R.M.;
RT "Characterization of the interaction between zyxin and members of the
RT Ena/vasodilator-stimulated phosphoprotein family of proteins.";
RL J. Biol. Chem. 275:22503-22511(2000).
RN [13]
RP INTERACTION WITH LPP.
RX PubMed=10637295; DOI=10.1091/mbc.11.1.117;
RA Petit M.M., Fradelizi J., Golsteyn R.M., Ayoubi T.A., Menichi B.,
RA Louvard D., Van de Ven W.J.M., Friederich E.;
RT "LPP, an actin cytoskeleton protein related to zyxin, harbors a
RT nuclear export signal and transcriptional activation capacity.";
RL Mol. Biol. Cell 11:117-129(2000).
RN [14]
RP INTERACTION WITH RAPH1.
RX PubMed=15469845; DOI=10.1016/j.devcel.2004.07.024;
RA Krause M., Leslie J.D., Stewart M., Lafuente E.M., Valderrama F.,
RA Jagannathan R., Strasser G.A., Rubinson D.A., Liu H., Way M.,
RA Yaffe M.B., Boussiotis V.A., Gertler F.B.;
RT "Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of
RT lamellipodial dynamics.";
RL Dev. Cell 7:571-583(2004).
RN [15]
RP PHOSPHORYLATION BY PKC.
RX PubMed=14706852; DOI=10.1016/S0014-5793(03)01435-2;
RA Chitaley K., Chen L., Galler A., Walter U., Daum G., Clowes A.W.;
RT "Vasodilator-stimulated phosphoprotein is a substrate for protein
RT kinase C.";
RL FEBS Lett. 556:211-215(2004).
RN [16]
RP FUNCTION, LACK OF ACTIN NUCLEATION ACTIVITY, AND FUNCTION IN ACTIN
RP FILAMENT ELONGATION.
RX PubMed=15939738; DOI=10.1074/jbc.M503957200;
RA Barzik M., Kotova T.I., Higgs H.N., Hazelwood L., Hanein D.,
RA Gertler F.B., Schafer D.A.;
RT "Ena/VASP proteins enhance actin polymerization in the presence of
RT barbed end capping proteins.";
RL J. Biol. Chem. 280:28653-28662(2005).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [18]
RP PHOSPHORYLATION AT SER-157, AND SUBCELLULAR LOCATION.
RX PubMed=16197368; DOI=10.1042/BJ20050796;
RA Wentworth J.K., Pula G., Poole A.W.;
RT "Vasodilator-stimulated phosphoprotein (VASP) is phosphorylated on Ser
RT 157 by protein kinase C-dependent and -independent mechanisms in
RT thrombin-stimulated human platelets.";
RL Biochem. J. 393:555-564(2006).
RN [19]
RP INTERACTION WITH XIRP1.
RX PubMed=16631741; DOI=10.1016/j.yexcr.2006.03.015;
RA van der Ven P.F.M., Ehler E., Vakeel P., Eulitz S., Schenk J.A.,
RA Milting H., Micheel B., Fuerst D.O.;
RT "Unusual splicing events result in distinct Xin isoforms that
RT associate differentially with filamin c and Mena/VASP.";
RL Exp. Cell Res. 312:2154-2167(2006).
RN [20]
RP PHOSPHORYLATION AT THR-278, MUTAGENESIS OF SER-157; SER-239 AND
RP THR-278, AND FUNCTION.
RX PubMed=17082196; DOI=10.1074/jbc.M608866200;
RA Blume C., Benz P.M., Walter U., Ha J., Kemp B.E., Renne T.;
RT "AMP-activated protein kinase impairs endothelial actin cytoskeleton
RT assembly by phosphorylating vasodilator-stimulated phosphoprotein.";
RL J. Biol. Chem. 282:4601-4612(2007).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-157 AND
RP SER-239.
RX PubMed=18559661; DOI=10.2337/db08-0381;
RA Li Calzi S., Purich D.L., Chang K.H., Afzal A., Nakagawa T.,
RA Busik J.V., Agarwal A., Segal M.S., Grant M.B.;
RT "Carbon monoxide and nitric oxide mediate cytoskeletal reorganization
RT in microvascular cells via vasodilator-stimulated phosphoprotein
RT phosphorylation: evidence for blunted responsiveness in diabetes.";
RL Diabetes 57:2488-2494(2008).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-316 AND SER-322, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-283, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-316, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [31]
RP STRUCTURE BY NMR OF 1-115.
RX PubMed=10990454; DOI=10.1093/emboj/19.18.4903;
RA Ball L.J., Kuehne R., Hoffmann B., Haefner A., Schmieder P.,
RA Volkmer-Engert R., Hof M., Wahl M., Schneider-Mergener J., Walter U.,
RA Oschkinat H., Jarchau T.;
RT "Dual epitope recognition by the VASP EVH1 domain modulates
RT polyproline ligand specificity and binding affinity.";
RL EMBO J. 19:4903-4914(2000).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 336-380, TETRAMERIZATION, AND
RP MUTAGENESIS OF PHE-370.
RX PubMed=15569942; DOI=10.1073/pnas.0403069101;
RA Kuehnel K., Jarchau T., Wolf E., Schlichting I., Walter U.,
RA Wittinghofer A., Strelkov S.V.;
RT "The VASP tetramerization domain is a right-handed coiled coil based
RT on a 15-residue repeat.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17027-17032(2004).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 203-245 IN COMPLEXES WITH
RP PFN1 AND ACTIN, AND INTERACTION WITH PFN1 AND MONOMERIC ACTIN.
RX PubMed=17914456; DOI=10.1038/sj.emboj.7601874;
RA Ferron F., Rebowski G., Lee S.H., Dominguez R.;
RT "Structural basis for the recruitment of profilin-actin complexes
RT during filament elongation by Ena/VASP.";
RL EMBO J. 26:4597-4606(2007).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 199-214 IN COMPLEX WITH PFN1
RP AND ACTIN.
RX PubMed=18689676; DOI=10.1073/pnas.0805852105;
RA Baek K., Liu X., Ferron F., Shu S., Korn E.D., Dominguez R.;
RT "Modulation of actin structure and function by phosphorylation of Tyr-
RT 53 and profilin binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:11748-11753(2008).
CC -!- FUNCTION: Ena/VASP proteins are actin-associated proteins involved
CC in a range of processes dependent on cytoskeleton remodeling and
CC cell polarity such as axon guidance, lamellipodial and filopodial
CC dynamics, platelet activation and cell migration. VASP promotes
CC actin filament elongation. It protects the barbed end of growing
CC actin filaments against capping and increases the rate of actin
CC polymerization in the presence of capping protein. VASP stimulates
CC actin filament elongation by promoting the transfer of profilin-
CC bound actin monomers onto the barbed end of growing actin
CC filaments. Plays a role in actin-based mobility of Listeria
CC monocytogenes in host cells. Regulates actin dynamics in platelets
CC and plays an important role in regulating platelet aggregation.
CC -!- SUBUNIT: Homotetramer. Interacts with PFN1, PFN2, LPP, ACTN1 and
CC ACTG1. Interacts, via the EVH1 domain, with the Pro-rich regions
CC of ZYX. This interaction is important for targeting to focal
CC adhesions and the formation of actin-rich structures at the apical
CC surface of cells. Interacts, via the EVH1 domain, with the Pro-
CC rich domain of Listeria monocytogenes actA. Interacts with
CC APBB1IP. Interacts, via the Pro-rich domain, with the C-terminal
CC SH3 domain of DNMBP (By similarity).
CC -!- INTERACTION:
CC P22736:NR4A1; NbExp=2; IntAct=EBI-748201, EBI-721550;
CC Q92636:NSMAF; NbExp=2; IntAct=EBI-748201, EBI-2947053;
CC Q15418:RPS6KA1; NbExp=4; IntAct=EBI-748201, EBI-963034;
CC P12003:VCL (xeno); NbExp=2; IntAct=EBI-748201, EBI-1039563;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton. Cell
CC junction, focal adhesion. Cell junction, tight junction (By
CC similarity). Cell projection, lamellipodium membrane. Cell
CC projection, filopodium membrane. Note=Targeted to stress fibers
CC and focal adhesions through interaction with a number of proteins
CC including MRL family members. Localizes to the plasma membrane in
CC protruding lamellipodia and filopodial tips. Stimulation by
CC thrombin or PMA, also translocates VASP to focal adhesions.
CC Localized along the sides of actin filaments throughout the
CC peripheral cytoplasm under basal conditions.
CC -!- TISSUE SPECIFICITY: Highly expressed in platelets.
CC -!- DOMAIN: The EVH2 domain is comprised of 3 regions. Block A is a
CC thymosin-like domain required for G-actin binding. The KLKR motif
CC within this block is essential for the G-actin binding and for
CC actin polymerization. Block B is required for F-actin binding and
CC subcellular location, and Block C for tetramerization.
CC -!- DOMAIN: The WH1 domain mediates interaction with XIRP1.
CC -!- PTM: Major substrate for cAMP-dependent (PKA) and cGMP-dependent
CC protein kinase (PKG) in platelets. The preferred site for PKA is
CC Ser-157, the preferred site for PKG/PRKG1, Ser-239. In ADP-
CC activated platelets, phosphorylation by PKA or PKG on Ser-157
CC leads to fibrinogen receptor inhibition. Phosphorylation on Thr-
CC 278 requires prior phosphorylation on Ser-157 and Ser-239. In
CC response to phorbol ester (PMA) stimulation, phosphorylated by
CC PKC/PRKCA. In response to thrombin, phosphorylated by both PKC and
CC ROCK1. Phosphorylation at Thr-278 by AMPK does not require prior
CC phosphorylation at Ser-157 or Ser-239. Phosphorylation at Ser-157
CC by PKA is required for localization to the tight junctions in
CC epithelial cells. Phosphorylation modulates F-actin binding, actin
CC filament elongation and platelet activation. Phosphorylation at
CC Ser-322 by AMPK also alters actin filament binding. Carbon
CC monoxide (CO) promotes phosphorylation at Ser-157, while nitric
CC oxide (NO) promotes phosphorylation at Ser-157, but also at Ser-
CC 239. Response to NO and CO is blunted in platelets from diabetic
CC patients, and VASP is not phosphorylated efficiently at Ser-157
CC and Ser-239.
CC -!- MISCELLANEOUS: VASP phosphorylation is used to monitor the effect
CC of so-called antiplatelet drugs that reduce platelet reactivity
CC and are used to prevent stent thrombosis, strokes and heart
CC attacks in patients at risk for these problems.
CC -!- SIMILARITY: Belongs to the Ena/VASP family.
CC -!- SIMILARITY: Contains 1 WH1 domain.
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DR EMBL; Z46389; CAA86523.1; -; mRNA.
DR EMBL; CH471126; EAW57362.1; -; Genomic_DNA.
DR EMBL; AK314812; BAG37336.1; -; mRNA.
DR EMBL; BC026019; AAH26019.1; -; mRNA.
DR EMBL; BC038224; AAH38224.1; -; mRNA.
DR EMBL; X98534; CAA67147.2; -; Genomic_DNA.
DR EMBL; X98533; CAA67147.2; JOINED; Genomic_DNA.
DR PIR; S51797; S51797.
DR RefSeq; NP_003361.1; NM_003370.3.
DR UniGene; Hs.515469; -.
DR PDB; 1EGX; NMR; -; A=1-115.
DR PDB; 1JNG; Model; -; A=1-115.
DR PDB; 1USD; X-ray; 1.70 A; A=336-380.
DR PDB; 1USE; X-ray; 1.30 A; A=336-380.
DR PDB; 2PAV; X-ray; 1.80 A; V=199-214.
DR PDB; 2PBD; X-ray; 1.50 A; V=203-245.
DR PDB; 3CHW; X-ray; 2.30 A; V=199-214.
DR PDBsum; 1EGX; -.
DR PDBsum; 1JNG; -.
DR PDBsum; 1USD; -.
DR PDBsum; 1USE; -.
DR PDBsum; 2PAV; -.
DR PDBsum; 2PBD; -.
DR PDBsum; 3CHW; -.
DR ProteinModelPortal; P50552; -.
DR SMR; P50552; 1-115, 338-377.
DR DIP; DIP-44105N; -.
DR IntAct; P50552; 21.
DR MINT; MINT-1437861; -.
DR STRING; 9606.ENSP00000245932; -.
DR PhosphoSite; P50552; -.
DR DMDM; 1718079; -.
DR OGP; P50552; -.
DR PaxDb; P50552; -.
DR PeptideAtlas; P50552; -.
DR PRIDE; P50552; -.
DR Ensembl; ENST00000245932; ENSP00000245932; ENSG00000125753.
DR GeneID; 7408; -.
DR KEGG; hsa:7408; -.
DR UCSC; uc002pcg.3; human.
DR CTD; 7408; -.
DR GeneCards; GC19P046010; -.
DR HGNC; HGNC:12652; VASP.
DR HPA; CAB004612; -.
DR HPA; HPA005724; -.
DR MIM; 601703; gene.
DR neXtProt; NX_P50552; -.
DR PharmGKB; PA37276; -.
DR eggNOG; NOG265043; -.
DR HOGENOM; HOG000013015; -.
DR HOVERGEN; HBG006655; -.
DR InParanoid; P50552; -.
DR KO; K06274; -.
DR PhylomeDB; P50552; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; VASP; human.
DR EvolutionaryTrace; P50552; -.
DR GeneWiki; Vasodilator-stimulated_phosphoprotein; -.
DR GenomeRNAi; 7408; -.
DR NextBio; 29004; -.
DR PRO; PR:P50552; -.
DR ArrayExpress; P50552; -.
DR Bgee; P50552; -.
DR CleanEx; HS_VASP; -.
DR Genevestigator; P50552; -.
DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031527; C:filopodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005923; C:tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0008154; P:actin polymerization or depolymerization; IEA:InterPro.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR017354; Vasodilator_phosphoprotein.
DR InterPro; IPR014885; VASP_tetra.
DR InterPro; IPR000697; WH1/EVH1.
DR Pfam; PF08776; VASP_tetra; 1.
DR Pfam; PF00568; WH1; 1.
DR PIRSF; PIRSF038010; Vasodilator_Phospo; 1.
DR SMART; SM00461; WH1; 1.
DR PROSITE; PS50229; WH1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Cell junction;
KW Cell membrane; Cell projection; Coiled coil; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Membrane;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; SH3-binding;
KW Tight junction.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 380 Vasodilator-stimulated phosphoprotein.
FT /FTId=PRO_0000065767.
FT DOMAIN 2 113 WH1.
FT REPEAT 344 358 1.
FT REPEAT 359 373 2.
FT REGION 225 377 EVH2.
FT REGION 225 245 EVH2 block A.
FT REGION 259 278 EVH2 block B.
FT REGION 343 377 EVH2 block C.
FT REGION 344 373 2 X 15 AA tandem repeats of L-[EQ]-[KR]-
FT [MV]-K-[EQ]-E-[IL]-[IL]-E-[AEV]-[FV]-
FT [KRV]-[KQ]-E.
FT COILED 337 373 Potential.
FT MOTIF 234 237 KLKR.
FT COMPBIAS 118 216 Pro-rich.
FT COMPBIAS 215 222 Poly-Gly.
FT COMPBIAS 259 262 Poly-Gly.
FT COMPBIAS 322 325 Poly-Ser.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 39 39 Phosphotyrosine.
FT MOD_RES 157 157 Phosphoserine; by PKA, PKC, PKG/PRKG1 and
FT ROCK1.
FT MOD_RES 239 239 Phosphoserine; by PKA and PKG/PRKG1.
FT MOD_RES 278 278 Phosphothreonine; by PKA, PKG/PRKG1 and
FT AMPK.
FT MOD_RES 283 283 N6-acetyllysine.
FT MOD_RES 316 316 Phosphothreonine.
FT MOD_RES 322 322 Phosphoserine; by AMPK.
FT MOD_RES 323 323 Phosphoserine (By similarity).
FT VARIANT 104 104 A -> T (in dbSNP:rs10415373).
FT /FTId=VAR_048929.
FT VARIANT 140 140 Q -> H (in dbSNP:rs34345197).
FT /FTId=VAR_048930.
FT MUTAGEN 157 157 S->A: Promotes F-actin assembly; when
FT associated with A-239 and A-278.
FT Interferes with F-actin assembly; when
FT associated with A-239 and E-278.
FT MUTAGEN 239 239 S->A: Promotes F-actin assembly; when
FT associated with A-157 and A-278.
FT Interferes with F-actin assembly; when
FT associated with A-157 and E-278.
FT MUTAGEN 278 278 T->A: Promotes F-actin assembly; when
FT associated with A-157 and A-239.
FT MUTAGEN 278 278 T->E: Interferes with F-actin assembly;
FT when associated with A-157 and A-239.
FT MUTAGEN 370 370 F->A: Lower stability of tetramerization
FT domain.
FT MUTAGEN 370 370 F->I,K: No change in stability of
FT tetramerization domain.
FT CONFLICT 2 2 S -> SS (in Ref. 5; AAH26019).
FT CONFLICT 241 241 Missing (in Ref. 5; AAH26019).
FT STRAND 5 12
FT STRAND 14 16
FT TURN 18 20
FT STRAND 25 27
FT STRAND 34 41
FT TURN 42 45
FT STRAND 46 55
FT STRAND 60 66
FT STRAND 79 86
FT STRAND 88 95
FT HELIX 96 114
FT HELIX 226 231
FT HELIX 341 376
SQ SEQUENCE 380 AA; 39830 MW; 17634B8134DEBF59 CRC64;
MSETVICSSR ATVMLYDDGN KRWLPAGTGP QAFSRVQIYH NPTANSFRVV GRKMQPDQQV
VINCAIVRGV KYNQATPNFH QWRDARQVWG LNFGSKEDAA QFAAGMASAL EALEGGGPPP
PPALPTWSVP NGPSPEEVEQ QKRQQPGPSE HIERRVSNAG GPPAPPAGGP PPPPGPPPPP
GPPPPPGLPP SGVPAAAHGA GGGPPPAPPL PAAQGPGGGG AGAPGLAAAI AGAKLRKVSK
QEEASGGPTA PKAESGRSGG GGLMEEMNAM LARRRKATQV GEKTPKDESA NQEEPEARVP
AQSESVRRPW EKNSTTLPRM KSSSSVTTSE TQPCTPSSSD YSDLQRVKQE LLEEVKKELQ
KVKEEIIEAF VQELRKRGSP
//
ID VASP_HUMAN Reviewed; 380 AA.
AC P50552; B2RBT9; Q6PIZ1; Q93035;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Vasodilator-stimulated phosphoprotein;
DE Short=VASP;
GN Name=VASP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 11-32; 87-96; 140-154;
RP 255-282 AND 297-322, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP POSSIBLE FUNCTION.
RC TISSUE=Promyelocyte;
RX PubMed=7828592;
RA Haffner C., Jarchau T., Reinhard M., Hoppe J., Lohmann S.M.,
RA Walter U.;
RT "Molecular cloning, structural analysis and functional expression of
RT the proline-rich focal adhesion and microfilament-associated protein
RT VASP.";
RL EMBO J. 14:19-27(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH
RP L.MONOCYTOGENES ACTA.
RX PubMed=10087267; DOI=10.1083/jcb.144.6.1245;
RA Laurent V., Loisel T.P., Harbeck B., Wehman A., Groebe L.,
RA Jockusch B.M., Wehland J., Gertler F.B., Carlier M.-F.;
RT "Role of proteins of the Ena/VASP family in actin-based motility of
RT Listeria monocytogenes.";
RL J. Cell Biol. 144:1245-1258(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Substantia nigra;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal lung, Fetal spleen, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 2-10, AND ACETYLATION AT SER-2.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3-380.
RX PubMed=8812448; DOI=10.1006/geno.1996.0457;
RA Zimmer M., Fink T., Fischer L., Hauser W., Scherer K., Lichter P.,
RA Walter U.;
RT "Cloning of the VASP (vasodilator-stimulated phosphoprotein) genes in
RT human and mouse: structure, sequence, and chromosomal localization.";
RL Genomics 36:227-233(1996).
RN [8]
RP PROTEIN SEQUENCE OF 143-164; 235-244 AND 267-285, AND PHOSPHORYLATION
RP AT SER-157; SER-239 AND THR-278 BY PRKG1.
RX PubMed=8182057;
RA Butt E., Abel K., Krieger M., Palm D., Hoppe V., Hoppe J., Walter U.;
RT "cAMP- and cGMP-dependent protein kinase phosphorylation sites of the
RT focal adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro
RT and in intact human platelets.";
RL J. Biol. Chem. 269:14509-14517(1994).
RN [9]
RP PHOSPHORYLATION AT SER-157, AND FIBRINOGEN RECEPTOR INHIBITION.
RX PubMed=7925440; DOI=10.1111/j.1432-1033.1994.00021.x;
RA Horstrup K., Jablonka B., Honig-Liedl P., Just M., Kochsiek K.,
RA Walter U.;
RT "Phosphorylation of focal adhesion vasodilator-stimulated
RT phosphoprotein at Ser157 in intact human platelets correlates with
RT fibrinogen receptor inhibition.";
RL Eur. J. Biochem. 225:21-27(1994).
RN [10]
RP INTERACTION WITH ACTG1 AND PFN1.
RX PubMed=7737110;
RA Reinhard M., Giehl K., Abel K., Haffner C., Jarchau T., Hoppe V.,
RA Jockusch B.M., Walter U.;
RT "The proline-rich focal adhesion and microfilament protein VASP is a
RT ligand for profilins.";
RL EMBO J. 14:1583-1589(1995).
RN [11]
RP FUNCTION OF EVH2 DOMAIN.
RX PubMed=10438535; DOI=10.1074/jbc.274.33.23549;
RA Bachmann C., Fischer L., Walter U., Reinhard M.;
RT "The EVH2 domain of the vasodilator-stimulated phosphoprotein mediates
RT tetramerization, F-actin binding, and actin bundle formation.";
RL J. Biol. Chem. 274:23549-23557(1999).
RN [12]
RP INTERACTION WITH ZYX.
RX PubMed=10801818; DOI=10.1074/jbc.M001698200;
RA Drees B., Friederich E., Fradelizi J., Louvard D., Beckerle M.C.,
RA Golsteyn R.M.;
RT "Characterization of the interaction between zyxin and members of the
RT Ena/vasodilator-stimulated phosphoprotein family of proteins.";
RL J. Biol. Chem. 275:22503-22511(2000).
RN [13]
RP INTERACTION WITH LPP.
RX PubMed=10637295; DOI=10.1091/mbc.11.1.117;
RA Petit M.M., Fradelizi J., Golsteyn R.M., Ayoubi T.A., Menichi B.,
RA Louvard D., Van de Ven W.J.M., Friederich E.;
RT "LPP, an actin cytoskeleton protein related to zyxin, harbors a
RT nuclear export signal and transcriptional activation capacity.";
RL Mol. Biol. Cell 11:117-129(2000).
RN [14]
RP INTERACTION WITH RAPH1.
RX PubMed=15469845; DOI=10.1016/j.devcel.2004.07.024;
RA Krause M., Leslie J.D., Stewart M., Lafuente E.M., Valderrama F.,
RA Jagannathan R., Strasser G.A., Rubinson D.A., Liu H., Way M.,
RA Yaffe M.B., Boussiotis V.A., Gertler F.B.;
RT "Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of
RT lamellipodial dynamics.";
RL Dev. Cell 7:571-583(2004).
RN [15]
RP PHOSPHORYLATION BY PKC.
RX PubMed=14706852; DOI=10.1016/S0014-5793(03)01435-2;
RA Chitaley K., Chen L., Galler A., Walter U., Daum G., Clowes A.W.;
RT "Vasodilator-stimulated phosphoprotein is a substrate for protein
RT kinase C.";
RL FEBS Lett. 556:211-215(2004).
RN [16]
RP FUNCTION, LACK OF ACTIN NUCLEATION ACTIVITY, AND FUNCTION IN ACTIN
RP FILAMENT ELONGATION.
RX PubMed=15939738; DOI=10.1074/jbc.M503957200;
RA Barzik M., Kotova T.I., Higgs H.N., Hazelwood L., Hanein D.,
RA Gertler F.B., Schafer D.A.;
RT "Ena/VASP proteins enhance actin polymerization in the presence of
RT barbed end capping proteins.";
RL J. Biol. Chem. 280:28653-28662(2005).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [18]
RP PHOSPHORYLATION AT SER-157, AND SUBCELLULAR LOCATION.
RX PubMed=16197368; DOI=10.1042/BJ20050796;
RA Wentworth J.K., Pula G., Poole A.W.;
RT "Vasodilator-stimulated phosphoprotein (VASP) is phosphorylated on Ser
RT 157 by protein kinase C-dependent and -independent mechanisms in
RT thrombin-stimulated human platelets.";
RL Biochem. J. 393:555-564(2006).
RN [19]
RP INTERACTION WITH XIRP1.
RX PubMed=16631741; DOI=10.1016/j.yexcr.2006.03.015;
RA van der Ven P.F.M., Ehler E., Vakeel P., Eulitz S., Schenk J.A.,
RA Milting H., Micheel B., Fuerst D.O.;
RT "Unusual splicing events result in distinct Xin isoforms that
RT associate differentially with filamin c and Mena/VASP.";
RL Exp. Cell Res. 312:2154-2167(2006).
RN [20]
RP PHOSPHORYLATION AT THR-278, MUTAGENESIS OF SER-157; SER-239 AND
RP THR-278, AND FUNCTION.
RX PubMed=17082196; DOI=10.1074/jbc.M608866200;
RA Blume C., Benz P.M., Walter U., Ha J., Kemp B.E., Renne T.;
RT "AMP-activated protein kinase impairs endothelial actin cytoskeleton
RT assembly by phosphorylating vasodilator-stimulated phosphoprotein.";
RL J. Biol. Chem. 282:4601-4612(2007).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-157 AND
RP SER-239.
RX PubMed=18559661; DOI=10.2337/db08-0381;
RA Li Calzi S., Purich D.L., Chang K.H., Afzal A., Nakagawa T.,
RA Busik J.V., Agarwal A., Segal M.S., Grant M.B.;
RT "Carbon monoxide and nitric oxide mediate cytoskeletal reorganization
RT in microvascular cells via vasodilator-stimulated phosphoprotein
RT phosphorylation: evidence for blunted responsiveness in diabetes.";
RL Diabetes 57:2488-2494(2008).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-316 AND SER-322, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-283, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-316, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [31]
RP STRUCTURE BY NMR OF 1-115.
RX PubMed=10990454; DOI=10.1093/emboj/19.18.4903;
RA Ball L.J., Kuehne R., Hoffmann B., Haefner A., Schmieder P.,
RA Volkmer-Engert R., Hof M., Wahl M., Schneider-Mergener J., Walter U.,
RA Oschkinat H., Jarchau T.;
RT "Dual epitope recognition by the VASP EVH1 domain modulates
RT polyproline ligand specificity and binding affinity.";
RL EMBO J. 19:4903-4914(2000).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 336-380, TETRAMERIZATION, AND
RP MUTAGENESIS OF PHE-370.
RX PubMed=15569942; DOI=10.1073/pnas.0403069101;
RA Kuehnel K., Jarchau T., Wolf E., Schlichting I., Walter U.,
RA Wittinghofer A., Strelkov S.V.;
RT "The VASP tetramerization domain is a right-handed coiled coil based
RT on a 15-residue repeat.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17027-17032(2004).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 203-245 IN COMPLEXES WITH
RP PFN1 AND ACTIN, AND INTERACTION WITH PFN1 AND MONOMERIC ACTIN.
RX PubMed=17914456; DOI=10.1038/sj.emboj.7601874;
RA Ferron F., Rebowski G., Lee S.H., Dominguez R.;
RT "Structural basis for the recruitment of profilin-actin complexes
RT during filament elongation by Ena/VASP.";
RL EMBO J. 26:4597-4606(2007).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 199-214 IN COMPLEX WITH PFN1
RP AND ACTIN.
RX PubMed=18689676; DOI=10.1073/pnas.0805852105;
RA Baek K., Liu X., Ferron F., Shu S., Korn E.D., Dominguez R.;
RT "Modulation of actin structure and function by phosphorylation of Tyr-
RT 53 and profilin binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:11748-11753(2008).
CC -!- FUNCTION: Ena/VASP proteins are actin-associated proteins involved
CC in a range of processes dependent on cytoskeleton remodeling and
CC cell polarity such as axon guidance, lamellipodial and filopodial
CC dynamics, platelet activation and cell migration. VASP promotes
CC actin filament elongation. It protects the barbed end of growing
CC actin filaments against capping and increases the rate of actin
CC polymerization in the presence of capping protein. VASP stimulates
CC actin filament elongation by promoting the transfer of profilin-
CC bound actin monomers onto the barbed end of growing actin
CC filaments. Plays a role in actin-based mobility of Listeria
CC monocytogenes in host cells. Regulates actin dynamics in platelets
CC and plays an important role in regulating platelet aggregation.
CC -!- SUBUNIT: Homotetramer. Interacts with PFN1, PFN2, LPP, ACTN1 and
CC ACTG1. Interacts, via the EVH1 domain, with the Pro-rich regions
CC of ZYX. This interaction is important for targeting to focal
CC adhesions and the formation of actin-rich structures at the apical
CC surface of cells. Interacts, via the EVH1 domain, with the Pro-
CC rich domain of Listeria monocytogenes actA. Interacts with
CC APBB1IP. Interacts, via the Pro-rich domain, with the C-terminal
CC SH3 domain of DNMBP (By similarity).
CC -!- INTERACTION:
CC P22736:NR4A1; NbExp=2; IntAct=EBI-748201, EBI-721550;
CC Q92636:NSMAF; NbExp=2; IntAct=EBI-748201, EBI-2947053;
CC Q15418:RPS6KA1; NbExp=4; IntAct=EBI-748201, EBI-963034;
CC P12003:VCL (xeno); NbExp=2; IntAct=EBI-748201, EBI-1039563;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton. Cell
CC junction, focal adhesion. Cell junction, tight junction (By
CC similarity). Cell projection, lamellipodium membrane. Cell
CC projection, filopodium membrane. Note=Targeted to stress fibers
CC and focal adhesions through interaction with a number of proteins
CC including MRL family members. Localizes to the plasma membrane in
CC protruding lamellipodia and filopodial tips. Stimulation by
CC thrombin or PMA, also translocates VASP to focal adhesions.
CC Localized along the sides of actin filaments throughout the
CC peripheral cytoplasm under basal conditions.
CC -!- TISSUE SPECIFICITY: Highly expressed in platelets.
CC -!- DOMAIN: The EVH2 domain is comprised of 3 regions. Block A is a
CC thymosin-like domain required for G-actin binding. The KLKR motif
CC within this block is essential for the G-actin binding and for
CC actin polymerization. Block B is required for F-actin binding and
CC subcellular location, and Block C for tetramerization.
CC -!- DOMAIN: The WH1 domain mediates interaction with XIRP1.
CC -!- PTM: Major substrate for cAMP-dependent (PKA) and cGMP-dependent
CC protein kinase (PKG) in platelets. The preferred site for PKA is
CC Ser-157, the preferred site for PKG/PRKG1, Ser-239. In ADP-
CC activated platelets, phosphorylation by PKA or PKG on Ser-157
CC leads to fibrinogen receptor inhibition. Phosphorylation on Thr-
CC 278 requires prior phosphorylation on Ser-157 and Ser-239. In
CC response to phorbol ester (PMA) stimulation, phosphorylated by
CC PKC/PRKCA. In response to thrombin, phosphorylated by both PKC and
CC ROCK1. Phosphorylation at Thr-278 by AMPK does not require prior
CC phosphorylation at Ser-157 or Ser-239. Phosphorylation at Ser-157
CC by PKA is required for localization to the tight junctions in
CC epithelial cells. Phosphorylation modulates F-actin binding, actin
CC filament elongation and platelet activation. Phosphorylation at
CC Ser-322 by AMPK also alters actin filament binding. Carbon
CC monoxide (CO) promotes phosphorylation at Ser-157, while nitric
CC oxide (NO) promotes phosphorylation at Ser-157, but also at Ser-
CC 239. Response to NO and CO is blunted in platelets from diabetic
CC patients, and VASP is not phosphorylated efficiently at Ser-157
CC and Ser-239.
CC -!- MISCELLANEOUS: VASP phosphorylation is used to monitor the effect
CC of so-called antiplatelet drugs that reduce platelet reactivity
CC and are used to prevent stent thrombosis, strokes and heart
CC attacks in patients at risk for these problems.
CC -!- SIMILARITY: Belongs to the Ena/VASP family.
CC -!- SIMILARITY: Contains 1 WH1 domain.
CC -----------------------------------------------------------------------
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DR EMBL; Z46389; CAA86523.1; -; mRNA.
DR EMBL; CH471126; EAW57362.1; -; Genomic_DNA.
DR EMBL; AK314812; BAG37336.1; -; mRNA.
DR EMBL; BC026019; AAH26019.1; -; mRNA.
DR EMBL; BC038224; AAH38224.1; -; mRNA.
DR EMBL; X98534; CAA67147.2; -; Genomic_DNA.
DR EMBL; X98533; CAA67147.2; JOINED; Genomic_DNA.
DR PIR; S51797; S51797.
DR RefSeq; NP_003361.1; NM_003370.3.
DR UniGene; Hs.515469; -.
DR PDB; 1EGX; NMR; -; A=1-115.
DR PDB; 1JNG; Model; -; A=1-115.
DR PDB; 1USD; X-ray; 1.70 A; A=336-380.
DR PDB; 1USE; X-ray; 1.30 A; A=336-380.
DR PDB; 2PAV; X-ray; 1.80 A; V=199-214.
DR PDB; 2PBD; X-ray; 1.50 A; V=203-245.
DR PDB; 3CHW; X-ray; 2.30 A; V=199-214.
DR PDBsum; 1EGX; -.
DR PDBsum; 1JNG; -.
DR PDBsum; 1USD; -.
DR PDBsum; 1USE; -.
DR PDBsum; 2PAV; -.
DR PDBsum; 2PBD; -.
DR PDBsum; 3CHW; -.
DR ProteinModelPortal; P50552; -.
DR SMR; P50552; 1-115, 338-377.
DR DIP; DIP-44105N; -.
DR IntAct; P50552; 21.
DR MINT; MINT-1437861; -.
DR STRING; 9606.ENSP00000245932; -.
DR PhosphoSite; P50552; -.
DR DMDM; 1718079; -.
DR OGP; P50552; -.
DR PaxDb; P50552; -.
DR PeptideAtlas; P50552; -.
DR PRIDE; P50552; -.
DR Ensembl; ENST00000245932; ENSP00000245932; ENSG00000125753.
DR GeneID; 7408; -.
DR KEGG; hsa:7408; -.
DR UCSC; uc002pcg.3; human.
DR CTD; 7408; -.
DR GeneCards; GC19P046010; -.
DR HGNC; HGNC:12652; VASP.
DR HPA; CAB004612; -.
DR HPA; HPA005724; -.
DR MIM; 601703; gene.
DR neXtProt; NX_P50552; -.
DR PharmGKB; PA37276; -.
DR eggNOG; NOG265043; -.
DR HOGENOM; HOG000013015; -.
DR HOVERGEN; HBG006655; -.
DR InParanoid; P50552; -.
DR KO; K06274; -.
DR PhylomeDB; P50552; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; VASP; human.
DR EvolutionaryTrace; P50552; -.
DR GeneWiki; Vasodilator-stimulated_phosphoprotein; -.
DR GenomeRNAi; 7408; -.
DR NextBio; 29004; -.
DR PRO; PR:P50552; -.
DR ArrayExpress; P50552; -.
DR Bgee; P50552; -.
DR CleanEx; HS_VASP; -.
DR Genevestigator; P50552; -.
DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031527; C:filopodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005923; C:tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0008154; P:actin polymerization or depolymerization; IEA:InterPro.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR017354; Vasodilator_phosphoprotein.
DR InterPro; IPR014885; VASP_tetra.
DR InterPro; IPR000697; WH1/EVH1.
DR Pfam; PF08776; VASP_tetra; 1.
DR Pfam; PF00568; WH1; 1.
DR PIRSF; PIRSF038010; Vasodilator_Phospo; 1.
DR SMART; SM00461; WH1; 1.
DR PROSITE; PS50229; WH1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Cell junction;
KW Cell membrane; Cell projection; Coiled coil; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Membrane;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; SH3-binding;
KW Tight junction.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 380 Vasodilator-stimulated phosphoprotein.
FT /FTId=PRO_0000065767.
FT DOMAIN 2 113 WH1.
FT REPEAT 344 358 1.
FT REPEAT 359 373 2.
FT REGION 225 377 EVH2.
FT REGION 225 245 EVH2 block A.
FT REGION 259 278 EVH2 block B.
FT REGION 343 377 EVH2 block C.
FT REGION 344 373 2 X 15 AA tandem repeats of L-[EQ]-[KR]-
FT [MV]-K-[EQ]-E-[IL]-[IL]-E-[AEV]-[FV]-
FT [KRV]-[KQ]-E.
FT COILED 337 373 Potential.
FT MOTIF 234 237 KLKR.
FT COMPBIAS 118 216 Pro-rich.
FT COMPBIAS 215 222 Poly-Gly.
FT COMPBIAS 259 262 Poly-Gly.
FT COMPBIAS 322 325 Poly-Ser.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 39 39 Phosphotyrosine.
FT MOD_RES 157 157 Phosphoserine; by PKA, PKC, PKG/PRKG1 and
FT ROCK1.
FT MOD_RES 239 239 Phosphoserine; by PKA and PKG/PRKG1.
FT MOD_RES 278 278 Phosphothreonine; by PKA, PKG/PRKG1 and
FT AMPK.
FT MOD_RES 283 283 N6-acetyllysine.
FT MOD_RES 316 316 Phosphothreonine.
FT MOD_RES 322 322 Phosphoserine; by AMPK.
FT MOD_RES 323 323 Phosphoserine (By similarity).
FT VARIANT 104 104 A -> T (in dbSNP:rs10415373).
FT /FTId=VAR_048929.
FT VARIANT 140 140 Q -> H (in dbSNP:rs34345197).
FT /FTId=VAR_048930.
FT MUTAGEN 157 157 S->A: Promotes F-actin assembly; when
FT associated with A-239 and A-278.
FT Interferes with F-actin assembly; when
FT associated with A-239 and E-278.
FT MUTAGEN 239 239 S->A: Promotes F-actin assembly; when
FT associated with A-157 and A-278.
FT Interferes with F-actin assembly; when
FT associated with A-157 and E-278.
FT MUTAGEN 278 278 T->A: Promotes F-actin assembly; when
FT associated with A-157 and A-239.
FT MUTAGEN 278 278 T->E: Interferes with F-actin assembly;
FT when associated with A-157 and A-239.
FT MUTAGEN 370 370 F->A: Lower stability of tetramerization
FT domain.
FT MUTAGEN 370 370 F->I,K: No change in stability of
FT tetramerization domain.
FT CONFLICT 2 2 S -> SS (in Ref. 5; AAH26019).
FT CONFLICT 241 241 Missing (in Ref. 5; AAH26019).
FT STRAND 5 12
FT STRAND 14 16
FT TURN 18 20
FT STRAND 25 27
FT STRAND 34 41
FT TURN 42 45
FT STRAND 46 55
FT STRAND 60 66
FT STRAND 79 86
FT STRAND 88 95
FT HELIX 96 114
FT HELIX 226 231
FT HELIX 341 376
SQ SEQUENCE 380 AA; 39830 MW; 17634B8134DEBF59 CRC64;
MSETVICSSR ATVMLYDDGN KRWLPAGTGP QAFSRVQIYH NPTANSFRVV GRKMQPDQQV
VINCAIVRGV KYNQATPNFH QWRDARQVWG LNFGSKEDAA QFAAGMASAL EALEGGGPPP
PPALPTWSVP NGPSPEEVEQ QKRQQPGPSE HIERRVSNAG GPPAPPAGGP PPPPGPPPPP
GPPPPPGLPP SGVPAAAHGA GGGPPPAPPL PAAQGPGGGG AGAPGLAAAI AGAKLRKVSK
QEEASGGPTA PKAESGRSGG GGLMEEMNAM LARRRKATQV GEKTPKDESA NQEEPEARVP
AQSESVRRPW EKNSTTLPRM KSSSSVTTSE TQPCTPSSSD YSDLQRVKQE LLEEVKKELQ
KVKEEIIEAF VQELRKRGSP
//
MIM
601703
*RECORD*
*FIELD* NO
601703
*FIELD* TI
*601703 VASODILATOR-STIMULATED PHOSPHOPROTEIN; VASP
*FIELD* TX
DESCRIPTION
Human platelet activation is inhibited by agents such as prostaglandins
read moreand NO donors, which elevate cAMP or cGMP levels. The
vasodilator-stimulated phosphoprotein (VASP) is phosphorylated in human
platelets in response to both cAMP- and cGMP-elevating agents, and its
phosphorylation correlates with platelet inhibition (summary by Haffner
et al., 1995).
CLONING
Haffner et al. (1995) cloned the VASP gene from human and canine cells
and showed that VASP is a 380-amino acid protein with a predicted
molecular mass of 39.8 kD.
Zimmer et al. (1996) cloned human and mouse VASP from genomic cosmid
libraries. They determined that the human and mouse VASP genes are 89%
identical at the amino acid level.
GENE FUNCTION
Brindle et al. (1996) showed that VASP binds to the proline-rich domain
of vinculin (193065). They suggested that this interaction is important
for actin-filament assembly and focal adhesion stability.
Kanchanawong et al. (2010) used 3-dimensional super-resolution
fluorescence microscopy to map nanoscale protein organization in focal
adhesions. Their results revealed that integrins and actin are
vertically separated by an approximately 40-nm focal adhesion core
region consisting of multiple protein-specific strata: a
membrane-apposed integrin signaling layer containing integrin
cytoplasmic tails (see 193210), focal adhesion kinase (600758), and
paxillin (602505); an intermediate force-transduction layer containing
talin (186745) and vinculin; and an uppermost actin-regulatory layer
containing zyxin (602002), VASP, and alpha-actinin (102575). By
localizing amino- and carboxy-terminally tagged talins, Kanchanawong et
al. (2010) revealed talin's polarized orientation, indicative of a role
in organizing the focal adhesion strata. Kanchanawong et al. (2010)
concluded that their composite multilaminar protein architecture
provided a molecular blueprint for understanding focal adhesion
functions.
GENE STRUCTURE
Zimmer et al. (1996) determined that human and mouse VASP consist of 13
exons and span a genomic DNA region of approximately 20 kb.
MAPPING
Zimmer et al. (1996) mapped human VASP to chromosome 19q13.2-q13.3 using
fluorescence in situ hybridization. They noted that VASP is located
about 92 kb distal to ERCC1 (126380) and about 300 kb proximal to the
myotonic dystrophy protein kinase gene (160900).
*FIELD* RF
1. Brindle, N. P. J.; Holt, M. R.; Davies, J. E.; Price, C. J.; Critchley,
D. R.: The focal-adhesion vasodilator-stimulated phosphoprotein (VASP)
binds to the proline-rich domain in vinculin. Biochem. J. 318: 753-757,
1996.
2. Haffner, C.; Jarchau, T.; Reinhard, M.; Hoppe, J.; Lohmann, S.
M.; Walter, V.: Molecular cloning, structural analysis and functional
expression of the proline-rich focal adhesion and microfilament-associated
protein VASP. EMBO J. 14: 19-27, 1995.
3. Kanchanawong, P.; Shtengel, G.; Pasapera, A. M.; Ramko, E. B.;
Davidson, M. W.; Hess, H. F.; Waterman, C. M.: Nanoscale architecture
of integrin-based cell adhesions. Nature 468: 580-584, 2010.
4. Zimmer, M.; Fink, T.; Fischer, L.; Hauser, W.; Scherer, K.; Lichter,
P.; Walter, U.: Cloning of the VASP (vasodilator-stimulated phosphoprotein)
genes in human and mouse: structure, sequence, and chromosomal localization. Genomics 36:
227-233, 1996.
*FIELD* CN
Ada Hamosh - updated: 2/2/2011
Jennifer P. Macke - updated: 3/21/1997
*FIELD* CD
Lori M. Kelman: 3/11/1997
*FIELD* ED
alopez: 03/08/2012
alopez: 2/7/2011
terry: 2/2/2011
alopez: 4/27/2010
jenny: 6/17/1997
terry: 3/21/1997
jenny: 3/20/1997
jenny: 3/17/1997
jenny: 3/11/1997
*RECORD*
*FIELD* NO
601703
*FIELD* TI
*601703 VASODILATOR-STIMULATED PHOSPHOPROTEIN; VASP
*FIELD* TX
DESCRIPTION
Human platelet activation is inhibited by agents such as prostaglandins
read moreand NO donors, which elevate cAMP or cGMP levels. The
vasodilator-stimulated phosphoprotein (VASP) is phosphorylated in human
platelets in response to both cAMP- and cGMP-elevating agents, and its
phosphorylation correlates with platelet inhibition (summary by Haffner
et al., 1995).
CLONING
Haffner et al. (1995) cloned the VASP gene from human and canine cells
and showed that VASP is a 380-amino acid protein with a predicted
molecular mass of 39.8 kD.
Zimmer et al. (1996) cloned human and mouse VASP from genomic cosmid
libraries. They determined that the human and mouse VASP genes are 89%
identical at the amino acid level.
GENE FUNCTION
Brindle et al. (1996) showed that VASP binds to the proline-rich domain
of vinculin (193065). They suggested that this interaction is important
for actin-filament assembly and focal adhesion stability.
Kanchanawong et al. (2010) used 3-dimensional super-resolution
fluorescence microscopy to map nanoscale protein organization in focal
adhesions. Their results revealed that integrins and actin are
vertically separated by an approximately 40-nm focal adhesion core
region consisting of multiple protein-specific strata: a
membrane-apposed integrin signaling layer containing integrin
cytoplasmic tails (see 193210), focal adhesion kinase (600758), and
paxillin (602505); an intermediate force-transduction layer containing
talin (186745) and vinculin; and an uppermost actin-regulatory layer
containing zyxin (602002), VASP, and alpha-actinin (102575). By
localizing amino- and carboxy-terminally tagged talins, Kanchanawong et
al. (2010) revealed talin's polarized orientation, indicative of a role
in organizing the focal adhesion strata. Kanchanawong et al. (2010)
concluded that their composite multilaminar protein architecture
provided a molecular blueprint for understanding focal adhesion
functions.
GENE STRUCTURE
Zimmer et al. (1996) determined that human and mouse VASP consist of 13
exons and span a genomic DNA region of approximately 20 kb.
MAPPING
Zimmer et al. (1996) mapped human VASP to chromosome 19q13.2-q13.3 using
fluorescence in situ hybridization. They noted that VASP is located
about 92 kb distal to ERCC1 (126380) and about 300 kb proximal to the
myotonic dystrophy protein kinase gene (160900).
*FIELD* RF
1. Brindle, N. P. J.; Holt, M. R.; Davies, J. E.; Price, C. J.; Critchley,
D. R.: The focal-adhesion vasodilator-stimulated phosphoprotein (VASP)
binds to the proline-rich domain in vinculin. Biochem. J. 318: 753-757,
1996.
2. Haffner, C.; Jarchau, T.; Reinhard, M.; Hoppe, J.; Lohmann, S.
M.; Walter, V.: Molecular cloning, structural analysis and functional
expression of the proline-rich focal adhesion and microfilament-associated
protein VASP. EMBO J. 14: 19-27, 1995.
3. Kanchanawong, P.; Shtengel, G.; Pasapera, A. M.; Ramko, E. B.;
Davidson, M. W.; Hess, H. F.; Waterman, C. M.: Nanoscale architecture
of integrin-based cell adhesions. Nature 468: 580-584, 2010.
4. Zimmer, M.; Fink, T.; Fischer, L.; Hauser, W.; Scherer, K.; Lichter,
P.; Walter, U.: Cloning of the VASP (vasodilator-stimulated phosphoprotein)
genes in human and mouse: structure, sequence, and chromosomal localization. Genomics 36:
227-233, 1996.
*FIELD* CN
Ada Hamosh - updated: 2/2/2011
Jennifer P. Macke - updated: 3/21/1997
*FIELD* CD
Lori M. Kelman: 3/11/1997
*FIELD* ED
alopez: 03/08/2012
alopez: 2/7/2011
terry: 2/2/2011
alopez: 4/27/2010
jenny: 6/17/1997
terry: 3/21/1997
jenny: 3/20/1997
jenny: 3/17/1997
jenny: 3/11/1997