VASP_HUMAN
ID VASP_HUMAN Reviewed; 380 AA.
AC P50552; B2RBT9; Q6PIZ1; Q93035;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Vasodilator-stimulated phosphoprotein;
DE Short=VASP;
GN Name=VASP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 POSSIBLE
RP FUNCTION.
RC TISSUE=Promyelocyte;
RX PubMed=7828592; DOI=10.1002/j.1460-2075.1995.tb06971.x;
RA Haffner C., Jarchau T., Reinhard M., Hoppe J., Lohmann S.M., Walter U.;
RT "Molecular cloning, structural analysis and functional expression of the
RT proline-rich focal adhesion and microfilament-associated protein VASP.";
RL EMBO J. 14:19-27(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH L.MONOCYTOGENES
RP ACTA.
RX PubMed=10087267; DOI=10.1083/jcb.144.6.1245;
RA Laurent V., Loisel T.P., Harbeck B., Wehman A., Groebe L., Jockusch B.M.,
RA 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT 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 human
RT 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 AT
RP SER-157; SER-239 AND THR-278 BY PRKG1.
RX PubMed=8182057; DOI=10.1016/s0021-9258(17)36652-8;
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 focal
RT adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro and in
RT 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., Walter U.;
RT "Phosphorylation of focal adhesion vasodilator-stimulated phosphoprotein at
RT Ser157 in intact human platelets correlates with fibrinogen receptor
RT inhibition.";
RL Eur. J. Biochem. 225:21-27(1994).
RN [10]
RP INTERACTION WITH ACTG1 AND PFN1.
RX PubMed=7737110; DOI=10.1002/j.1460-2075.1995.tb07146.x;
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 ligand
RT 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 nuclear
RT 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., Yaffe M.B.,
RA 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 kinase
RT C.";
RL FEBS Lett. 556:211-215(2004).
RN [16]
RP FUNCTION, LACK OF ACTIN NUCLEATION ACTIVITY, AND FUNCTION IN ACTIN FILAMENT
RP ELONGATION.
RX PubMed=15939738; DOI=10.1074/jbc.m503957200;
RA Barzik M., Kotova T.I., Higgs H.N., Hazelwood L., Hanein D., Gertler F.B.,
RA Schafer D.A.;
RT "Ena/VASP proteins enhance actin polymerization in the presence of barbed
RT end capping proteins.";
RL J. Biol. Chem. 280:28653-28662(2005).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 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 157
RT by protein kinase C-dependent and -independent mechanisms in thrombin-
RT 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 associate
RT 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 THR-278,
RP 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 SER-239.
RX PubMed=18559661; DOI=10.2337/db08-0381;
RA Li Calzi S., Purich D.L., Chang K.H., Afzal A., Nakagawa T., Busik J.V.,
RA Agarwal A., Segal M.S., Grant M.B.;
RT "Carbon monoxide and nitric oxide mediate cytoskeletal reorganization in
RT 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [25]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MEFV.
RX PubMed=19109554; DOI=10.3181/0806-rm-184;
RA Waite A.L., Schaner P., Hu C., Richards N., Balci-Peynircioglu B., Hong A.,
RA Fox M., Gumucio D.L.;
RT "Pyrin and ASC co-localize to cellular sites that are rich in polymerizing
RT actin.";
RL Exp. Biol. Med. (Maywood) 234:40-52(2009).
RN [26]
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 [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-283, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-316, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [29]
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., Buerckstuemmer T.,
RA 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 [30]
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., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
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., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39; SER-46; SER-239; THR-284;
RP SER-305 AND SER-314, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [36]
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 polyproline
RT ligand specificity and binding affinity.";
RL EMBO J. 19:4903-4914(2000).
RN [37]
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 on a
RT 15-residue repeat.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17027-17032(2004).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 203-245 IN COMPLEXES WITH PFN1 AND
RP 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 during
RT filament elongation by Ena/VASP.";
RL EMBO J. 26:4597-4606(2007).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 199-214 IN COMPLEX WITH PFN1 AND
RP 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-53
RT 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 in a
CC range of processes dependent on cytoskeleton remodeling and cell
CC polarity such as axon guidance, lamellipodial and filopodial dynamics,
CC platelet activation and cell migration. VASP promotes actin filament
CC elongation. It protects the barbed end of growing actin filaments
CC against capping and increases the rate of actin polymerization in the
CC presence of capping protein. VASP stimulates actin filament elongation
CC by promoting the transfer of profilin-bound actin monomers onto the
CC barbed end of growing actin filaments. Plays a role in actin-based
CC mobility of Listeria monocytogenes in host cells. Regulates actin
CC dynamics in platelets and plays an important role in regulating
CC platelet aggregation. {ECO:0000269|PubMed:10087267,
CC ECO:0000269|PubMed:10438535, ECO:0000269|PubMed:15939738,
CC ECO:0000269|PubMed:17082196, ECO:0000269|PubMed:18559661}.
CC -!- SUBUNIT: Homotetramer. Interacts with PFN1, PFN2, LPP, ACTN1 and ACTG1.
CC Interacts, via the EVH1 domain, with the Pro-rich regions of ZYX. This
CC interaction is important for targeting to focal adhesions and the
CC formation of actin-rich structures at the apical surface of cells.
CC Interacts, via the EVH1 domain, with the Pro-rich domain of Listeria
CC monocytogenes actA. Interacts with APBB1IP. Interacts, via the Pro-rich
CC domain, with the C-terminal SH3 domain of DNMBP (By similarity).
CC Interacts weakly with MEFV. {ECO:0000250, ECO:0000269|PubMed:10087267,
CC ECO:0000269|PubMed:10637295, ECO:0000269|PubMed:10801818,
CC ECO:0000269|PubMed:15469845, ECO:0000269|PubMed:16631741,
CC ECO:0000269|PubMed:17914456, ECO:0000269|PubMed:18689676,
CC ECO:0000269|PubMed:19109554, ECO:0000269|PubMed:7737110}.
CC -!- INTERACTION:
CC P50552; Q8IZP0-5: ABI1; NbExp=3; IntAct=EBI-748201, EBI-11743294;
CC P50552; Q9NYB9: ABI2; NbExp=5; IntAct=EBI-748201, EBI-743598;
CC P50552; Q9P2A4: ABI3; NbExp=9; IntAct=EBI-748201, EBI-742038;
CC P50552; Q9UQB8-4: BAIAP2; NbExp=6; IntAct=EBI-748201, EBI-6174091;
CC P50552; O95684: CEP43; NbExp=3; IntAct=EBI-748201, EBI-1266334;
CC P50552; P22736: NR4A1; NbExp=2; IntAct=EBI-748201, EBI-721550;
CC P50552; Q92636: NSMAF; NbExp=2; IntAct=EBI-748201, EBI-2947053;
CC P50552; Q9UIG4: PSORS1C2; NbExp=4; IntAct=EBI-748201, EBI-11974061;
CC P50552; Q15418: RPS6KA1; NbExp=4; IntAct=EBI-748201, EBI-963034;
CC P50552; Q13296: SCGB2A2; NbExp=3; IntAct=EBI-748201, EBI-9058786;
CC P50552; Q9C026: TRIM9; NbExp=4; IntAct=EBI-748201, EBI-720828;
CC P50552; Q702N8: XIRP1; NbExp=5; IntAct=EBI-748201, EBI-7851194;
CC P50552; Q15942: ZYX; NbExp=4; IntAct=EBI-748201, EBI-444225;
CC P50552; P12003: VCL; Xeno; NbExp=2; IntAct=EBI-748201, EBI-1039563;
CC P50552; Q9RI12: ypkA; Xeno; NbExp=4; IntAct=EBI-748201, EBI-2849107;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton. Cell
CC junction, focal adhesion. Cell junction, tight junction {ECO:0000250}.
CC Cell projection, lamellipodium membrane. Cell projection, filopodium
CC membrane. Note=Targeted to stress fibers and focal adhesions through
CC interaction with a number of proteins including MRL family members.
CC Localizes to the plasma membrane in protruding lamellipodia and
CC filopodial tips. Stimulation by thrombin or PMA, also translocates VASP
CC to focal adhesions. Localized along the sides of actin filaments
CC throughout the peripheral cytoplasm under basal conditions. In pre-
CC apoptotic cells, colocalizes with MEFV in large specks (pyroptosomes).
CC -!- TISSUE SPECIFICITY: Highly expressed in platelets.
CC {ECO:0000269|PubMed:7828592}.
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 actin
CC polymerization. Block B is required for F-actin binding and subcellular
CC 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 Ser-
CC 157, the preferred site for PKG/PRKG1, Ser-239. In ADP-activated
CC platelets, phosphorylation by PKA or PKG on Ser-157 leads to fibrinogen
CC receptor inhibition. Phosphorylation on Thr-278 requires prior
CC phosphorylation on Ser-157 and Ser-239. In response to phorbol ester
CC (PMA) stimulation, phosphorylated by PKC/PRKCA. In response to
CC thrombin, phosphorylated by both PKC and ROCK1. Phosphorylation at Thr-
CC 278 by AMPK does not require prior phosphorylation at Ser-157 or Ser-
CC 239. Phosphorylation at Ser-157 by PKA is required for localization to
CC the tight junctions in epithelial cells. Phosphorylation modulates F-
CC actin binding, actin filament elongation and platelet activation.
CC Phosphorylation at Ser-322 by AMPK also alters actin filament binding.
CC Carbon monoxide (CO) promotes phosphorylation at Ser-157, while nitric
CC oxide (NO) promotes phosphorylation at Ser-157, but also at Ser-239.
CC Response to NO and CO is blunted in platelets from diabetic patients,
CC and VASP is not phosphorylated efficiently at Ser-157 and Ser-239.
CC {ECO:0000269|PubMed:14706852, ECO:0000269|PubMed:16197368,
CC ECO:0000269|PubMed:17082196, ECO:0000269|PubMed:18559661,
CC ECO:0000269|PubMed:7925440, ECO:0000269|PubMed:8182057}.
CC -!- MISCELLANEOUS: VASP phosphorylation is used to monitor the effect of
CC so-called antiplatelet drugs that reduce platelet reactivity and are
CC used to prevent stent thrombosis, strokes and heart attacks in patients
CC at risk for these problems.
CC -!- SIMILARITY: Belongs to the Ena/VASP family. {ECO:0000305}.
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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 CCDS; CCDS33051.1; -.
DR PIR; S51797; S51797.
DR RefSeq; NP_003361.1; NM_003370.3.
DR PDB; 1EGX; NMR; -; 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; 1USD; -.
DR PDBsum; 1USE; -.
DR PDBsum; 2PAV; -.
DR PDBsum; 2PBD; -.
DR PDBsum; 3CHW; -.
DR AlphaFoldDB; P50552; -.
DR BMRB; P50552; -.
DR SMR; P50552; -.
DR BioGRID; 113251; 265.
DR CORUM; P50552; -.
DR DIP; DIP-44105N; -.
DR ELM; P50552; -.
DR IntAct; P50552; 87.
DR MINT; P50552; -.
DR STRING; 9606.ENSP00000245932; -.
DR ChEMBL; CHEMBL4295774; -.
DR MoonDB; P50552; Predicted.
DR GlyGen; P50552; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P50552; -.
DR MetOSite; P50552; -.
DR PhosphoSitePlus; P50552; -.
DR BioMuta; VASP; -.
DR DMDM; 1718079; -.
DR OGP; P50552; -.
DR EPD; P50552; -.
DR jPOST; P50552; -.
DR MassIVE; P50552; -.
DR MaxQB; P50552; -.
DR PaxDb; P50552; -.
DR PeptideAtlas; P50552; -.
DR PRIDE; P50552; -.
DR ProteomicsDB; 56248; -.
DR TopDownProteomics; P50552; -.
DR Antibodypedia; 1491; 1135 antibodies from 46 providers.
DR DNASU; 7408; -.
DR Ensembl; ENST00000245932.11; ENSP00000245932.5; ENSG00000125753.14.
DR GeneID; 7408; -.
DR KEGG; hsa:7408; -.
DR MANE-Select; ENST00000245932.11; ENSP00000245932.5; NM_003370.4; NP_003361.1.
DR UCSC; uc002pcg.4; human.
DR CTD; 7408; -.
DR DisGeNET; 7408; -.
DR GeneCards; VASP; -.
DR HGNC; HGNC:12652; VASP.
DR HPA; ENSG00000125753; Low tissue specificity.
DR MIM; 601703; gene.
DR neXtProt; NX_P50552; -.
DR OpenTargets; ENSG00000125753; -.
DR PharmGKB; PA37276; -.
DR VEuPathDB; HostDB:ENSG00000125753; -.
DR eggNOG; KOG4590; Eukaryota.
DR GeneTree; ENSGT00940000156765; -.
DR HOGENOM; CLU_017790_0_0_1; -.
DR InParanoid; P50552; -.
DR OMA; TSEAHPC; -.
DR OrthoDB; 263288at2759; -.
DR PhylomeDB; P50552; -.
DR TreeFam; TF321411; -.
DR PathwayCommons; P50552; -.
DR Reactome; R-HSA-202433; Generation of second messenger molecules.
DR Reactome; R-HSA-376176; Signaling by ROBO receptors.
DR Reactome; R-HSA-446353; Cell-extracellular matrix interactions.
DR SignaLink; P50552; -.
DR SIGNOR; P50552; -.
DR BioGRID-ORCS; 7408; 12 hits in 1071 CRISPR screens.
DR ChiTaRS; VASP; human.
DR EvolutionaryTrace; P50552; -.
DR GeneWiki; Vasodilator-stimulated_phosphoprotein; -.
DR GenomeRNAi; 7408; -.
DR Pharos; P50552; Tbio.
DR PRO; PR:P50552; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P50552; protein.
DR Bgee; ENSG00000125753; Expressed in granulocyte and 174 other tissues.
DR ExpressionAtlas; P50552; baseline and differential.
DR Genevisible; P50552; HS.
DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005522; F:profilin binding; IPI:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IBA:GO_Central.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0008154; P:actin polymerization or depolymerization; IEA:InterPro.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0001843; P:neural tube closure; IBA:GO_Central.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IEA:InterPro.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR034367; VASP.
DR InterPro; IPR017354; VASP/EVL.
DR InterPro; IPR038023; VASP_sf.
DR InterPro; IPR014885; VASP_tetra.
DR InterPro; IPR000697; WH1/EVH1_dom.
DR PANTHER; PTHR11202:SF12; PTHR11202:SF12; 1.
DR Pfam; PF08776; VASP_tetra; 1.
DR Pfam; PF00568; WH1; 1.
DR PIRSF; PIRSF038010; Vasodilator_Phospo; 1.
DR SMART; SM00461; WH1; 1.
DR SUPFAM; SSF118370; SSF118370; 1.
DR PROSITE; PS50229; WH1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Cell junction; Cell membrane;
KW Cell projection; Coiled coil; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; SH3-binding; Tight junction.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..380
FT /note="Vasodilator-stimulated phosphoprotein"
FT /id="PRO_0000065767"
FT DOMAIN 2..113
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT REPEAT 344..358
FT /note="1"
FT REPEAT 359..373
FT /note="2"
FT REGION 111..343
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 225..377
FT /note="EVH2"
FT REGION 225..245
FT /note="EVH2 block A"
FT REGION 259..278
FT /note="EVH2 block B"
FT REGION 343..377
FT /note="EVH2 block C"
FT REGION 344..373
FT /note="2 X 15 AA tandem repeats of L-[EQ]-[KR]-[MV]-K-[EQ]-
FT E-[IL]-[IL]-E-[AEV]-[FV]-[KRV]-[KQ]-E"
FT COILED 337..373
FT /evidence="ECO:0000255"
FT MOTIF 234..237
FT /note="KLKR"
FT COMPBIAS 115..129
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 163..192
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..294
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 307..343
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 39
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 157
FT /note="Phosphoserine; by PKA, PKC, PKG/PRKG1 and ROCK1"
FT /evidence="ECO:0000269|PubMed:16197368,
FT ECO:0000269|PubMed:18559661, ECO:0000269|PubMed:7925440,
FT ECO:0000269|PubMed:8182057"
FT MOD_RES 239
FT /note="Phosphoserine; by PKA and PKG/PRKG1"
FT /evidence="ECO:0000269|PubMed:18559661,
FT ECO:0000269|PubMed:8182057, ECO:0007744|PubMed:23186163"
FT MOD_RES 278
FT /note="Phosphothreonine; by PKA, PKG/PRKG1 and AMPK"
FT /evidence="ECO:0000269|PubMed:17082196,
FT ECO:0000269|PubMed:8182057"
FT MOD_RES 283
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 284
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 305
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 316
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 322
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70460"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70460"
FT VARIANT 104
FT /note="A -> T (in dbSNP:rs10415373)"
FT /id="VAR_048929"
FT VARIANT 140
FT /note="Q -> H (in dbSNP:rs34345197)"
FT /id="VAR_048930"
FT MUTAGEN 157
FT /note="S->A: Promotes F-actin assembly; when associated
FT with A-239 and A-278. Interferes with F-actin assembly;
FT when associated with A-239 and E-278."
FT /evidence="ECO:0000269|PubMed:17082196"
FT MUTAGEN 239
FT /note="S->A: Promotes F-actin assembly; when associated
FT with A-157 and A-278. Interferes with F-actin assembly;
FT when associated with A-157 and E-278."
FT /evidence="ECO:0000269|PubMed:17082196"
FT MUTAGEN 278
FT /note="T->A: Promotes F-actin assembly; when associated
FT with A-157 and A-239."
FT /evidence="ECO:0000269|PubMed:17082196"
FT MUTAGEN 278
FT /note="T->E: Interferes with F-actin assembly; when
FT associated with A-157 and A-239."
FT /evidence="ECO:0000269|PubMed:17082196"
FT MUTAGEN 370
FT /note="F->A: Lower stability of tetramerization domain."
FT /evidence="ECO:0000269|PubMed:15569942"
FT MUTAGEN 370
FT /note="F->I,K: No change in stability of tetramerization
FT domain."
FT /evidence="ECO:0000269|PubMed:15569942"
FT CONFLICT 2
FT /note="S -> SS (in Ref. 5; AAH26019)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="Missing (in Ref. 5; AAH26019)"
FT /evidence="ECO:0000305"
FT STRAND 5..12
FT /evidence="ECO:0007829|PDB:1EGX"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:1EGX"
FT TURN 18..20
FT /evidence="ECO:0007829|PDB:1EGX"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:1EGX"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:1EGX"
FT TURN 42..45
FT /evidence="ECO:0007829|PDB:1EGX"
FT STRAND 46..55
FT /evidence="ECO:0007829|PDB:1EGX"
FT STRAND 60..66
FT /evidence="ECO:0007829|PDB:1EGX"
FT STRAND 79..86
FT /evidence="ECO:0007829|PDB:1EGX"
FT STRAND 88..95
FT /evidence="ECO:0007829|PDB:1EGX"
FT HELIX 96..114
FT /evidence="ECO:0007829|PDB:1EGX"
FT HELIX 226..231
FT /evidence="ECO:0007829|PDB:2PBD"
FT HELIX 341..376
FT /evidence="ECO:0007829|PDB:1USE"
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
