VINC_HUMAN
ID VINC_HUMAN Reviewed; 1134 AA.
AC P18206; Q16450; Q5SWX2; Q7Z3B8; Q8IXU7;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=Vinculin;
DE AltName: Full=Metavinculin;
DE Short=MV;
GN Name=VCL;
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] (ISOFORM 1).
RC TISSUE=Endothelial cell;
RX PubMed=2116004; DOI=10.1073/pnas.87.15.5667;
RA Weller P.A., Ogryzko E.P., Corben E.B., Zhidkova N.I., Patel B.,
RA Price G.J., Spurr N.K., Koteliansky V.E., Critchley D.R.;
RT "Complete sequence of human vinculin and assignment of the gene to
RT chromosome 10.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:5667-5671(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-234.
RC TISSUE=Prostate;
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-56, AND ALTERNATIVE SPLICING
RP (ISOFORMS 1 AND 2).
RX PubMed=8440716; DOI=10.1016/s0021-9258(18)53612-7;
RA Moiseyeva E.P., Weller P.A., Zhidkova N.I., Corben E.B., Patel B.,
RA Jasinska I., Koteliansky V.E., Critchley D.R.;
RT "Organization of the human gene encoding the cytoskeletal protein vinculin
RT and the sequence of the vinculin promoter.";
RL J. Biol. Chem. 268:4318-4325(1993).
RN [6]
RP PROTEIN SEQUENCE OF 114-132; 247-261; 327-339; 353-366; 465-476 AND
RP 548-561, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 854-1051, AND ALTERNATIVE SPLICING
RP (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=1339348; DOI=10.1111/j.1432-1033.1992.tb16692.x;
RA Koteliansky V.E., Ogryzko E.P., Zhidkova N.I., Weller P.A., Critchley D.R.,
RA Vancompernolle K., Vandekerckhove J., Strasser P., Way M., Gimona M.,
RA Small J.V.;
RT "An additional exon in the human vinculin gene specifically encodes meta-
RT vinculin-specific difference peptide. Cross-species comparison reveals
RT variable and conserved motifs in the meta-vinculin insert.";
RL Eur. J. Biochem. 204:767-772(1992).
RN [8]
RP PROTEIN SEQUENCE OF 2-7 (ISOFORMS 1/2).
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 [9]
RP PHOSPHORYLATION AT TYR-1133, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15229287; DOI=10.1091/mbc.e04-03-0264;
RA Zhang Z., Izaguirre G., Lin S.-Y., Lee H.Y., Schaefer E., Haimovich B.;
RT "The phosphorylation of vinculin on tyrosine residues 100 and 1065,
RT mediated by SRC kinases, affects cell spreading.";
RL Mol. Biol. Cell 15:4234-4247(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-721, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP INTERACTION WITH SYNM.
RX PubMed=18028034; DOI=10.1042/bj20071188;
RA Sun N., Critchley D.R., Paulin D., Li Z., Robson R.M.;
RT "Human alpha-synemin interacts directly with vinculin and metavinculin.";
RL Biochem. J. 409:657-667(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-290; SER-721 AND TYR-822, 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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-173 AND LYS-496, AND
RP IDENTIFICATION BY MASS 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 [14]
RP FUNCTION, AND DOMAIN.
RX PubMed=20484056; DOI=10.1074/jbc.m110.102830;
RA Le Clainche C., Dwivedi S.P., Didry D., Carlier M.F.;
RT "Vinculin is a dually regulated actin filament barbed end-capping and side-
RT binding protein.";
RL J. Biol. Chem. 285:23420-23432(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-288; SER-290 AND SER-721, AND
RP IDENTIFICATION BY 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 [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-290; SER-346; SER-434 AND
RP SER-721, AND 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 [18]
RP FUNCTION (ISOFORM 2).
RX PubMed=22613835; DOI=10.1083/jcb.201111046;
RA Janssen M.E., Liu H., Volkmann N., Hanein D.;
RT "The C-terminal tail domain of metavinculin, vinculin's splice variant,
RT severs actin filaments.";
RL J. Cell Biol. 197:585-593(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-288; THR-672 AND SER-721, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-260; SER-275; SER-288;
RP SER-290; SER-346; SER-579; SER-600; THR-604; SER-721; SER-795 AND SER-809,
RP AND 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 [21]
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 [22]
RP INTERACTION WITH CTNNA1.
RX PubMed=26691986; DOI=10.1038/ng.3474;
RA Saksens N.T., Krebs M.P., Schoenmaker-Koller F.E., Hicks W., Yu M., Shi L.,
RA Rowe L., Collin G.B., Charette J.R., Letteboer S.J., Neveling K.,
RA van Moorsel T.W., Abu-Ltaif S., De Baere E., Walraedt S., Banfi S.,
RA Simonelli F., Cremers F.P., Boon C.J., Roepman R., Leroy B.P.,
RA Peachey N.S., Hoyng C.B., Nishina P.M., den Hollander A.I.;
RT "Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed
RT retinal pigment epithelium integrity.";
RL Nat. Genet. 48:144-151(2016).
RN [23]
RP SUBUNIT.
RX PubMed=29069646; DOI=10.1159/000484298;
RA Rui Y.N., Xu Z., Fang X., Menezes M.R., Balzeau J., Niu A., Hagan J.P.,
RA Kim D.H.;
RT "The Intracranial Aneurysm Gene THSD1 Connects Endosome Dynamics to Nascent
RT Focal Adhesion Assembly.";
RL Cell. Physiol. Biochem. 43:2200-2211(2017).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 1-258 IN COMPLEX WITH TLN1.
RX PubMed=15070891; DOI=10.1074/jbc.m403076200;
RA Izard T., Vonrhein C.;
RT "Structural basis for amplifying vinculin activation by talin.";
RL J. Biol. Chem. 279:27667-27678(2004).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-258 IN COMPLEX WITH TLN1.
RX PubMed=14702644; DOI=10.1038/nature02281;
RA Izard T., Evans G., Borgon R.A., Rush C.L., Bricogne G., Bois P.R.J.;
RT "Vinculin activation by talin through helical bundle conversion.";
RL Nature 427:171-175(2004).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-258 IN COMPLEX WITH ACTN4, AND
RP INTERACTION WITH ACTN4.
RX PubMed=15988023; DOI=10.1128/mcb.25.14.6112-6122.2005;
RA Bois P.R.J., Borgon R.A., Vonrhein C., Izard T.;
RT "Structural dynamics of alpha-actinin-vinculin interactions.";
RL Mol. Cell. Biol. 25:6112-6122(2005).
RN [27]
RP VARIANTS CMD1W LEU-954 DEL AND TRP-975, AND CHARACTERIZATION OF VARIANT
RP CMD1W TRP-975.
RX PubMed=11815424; DOI=10.1161/hc0402.102930;
RA Olson T.M., Illenberger S., Kishimoto N.Y., Huttelmaier S., Keating M.T.,
RA Jockusch B.M.;
RT "Metavinculin mutations alter actin interaction in dilated
RT cardiomyopathy.";
RL Circulation 105:431-437(2002).
RN [28]
RP VARIANT CMD1W TRP-975, AND VARIANTS VAL-934 AND ALA-943.
RX PubMed=16236538; DOI=10.1016/j.ymgme.2005.08.006;
RA Vasile V.C., Will M.L., Ommen S.R., Edwards W.D., Olson T.M.,
RA Ackerman M.J.;
RT "Identification of a metavinculin missense mutation, R975W, associated with
RT both hypertrophic and dilated cardiomyopathy.";
RL Mol. Genet. Metab. 87:169-174(2006).
RN [29]
RP VARIANT CMH15 MET-277.
RX PubMed=16712796; DOI=10.1016/j.bbrc.2006.04.151;
RA Vasile V.C., Ommen S.R., Edwards W.D., Ackerman M.J.;
RT "A missense mutation in a ubiquitously expressed protein, vinculin, confers
RT susceptibility to hypertrophic cardiomyopathy.";
RL Biochem. Biophys. Res. Commun. 345:998-1003(2006).
CC -!- FUNCTION: Actin filament (F-actin)-binding protein involved in cell-
CC matrix adhesion and cell-cell adhesion. Regulates cell-surface E-
CC cadherin expression and potentiates mechanosensing by the E-cadherin
CC complex. May also play important roles in cell morphology and
CC locomotion. {ECO:0000269|PubMed:20484056}.
CC -!- SUBUNIT: Exhibits self-association properties. Part of a complex
CC composed of THSD1, PTK2/FAK1, TLN1 and VCL (PubMed:29069646). Interacts
CC with APBB1IP and NRAP (By similarity). Interacts with TLN1. Interacts
CC with CTNNB1 and this interaction is necessary for its localization to
CC the cell-cell junctions and for its function in regulating cell surface
CC expression of E-cadherin (By similarity). Interacts with SYNM.
CC Interacts with SORBS1 (By similarity). Interacts with CTNNA1
CC (PubMed:26691986). Binds to ACTN4; this interaction triggers
CC conformational changes (PubMed:15988023).
CC {ECO:0000250|UniProtKB:P12003, ECO:0000250|UniProtKB:Q64727,
CC ECO:0000269|PubMed:14702644, ECO:0000269|PubMed:15070891,
CC ECO:0000269|PubMed:15988023, ECO:0000269|PubMed:18028034,
CC ECO:0000269|PubMed:26691986, ECO:0000269|PubMed:29069646}.
CC -!- INTERACTION:
CC P18206; Q9NYB9: ABI2; NbExp=3; IntAct=EBI-716775, EBI-743598;
CC P18206; O15144: ARPC2; NbExp=2; IntAct=EBI-716775, EBI-352356;
CC P18206; Q969V4: TEKT1; NbExp=3; IntAct=EBI-716775, EBI-10180409;
CC P18206; P18010: ipaA; Xeno; NbExp=7; IntAct=EBI-716775, EBI-7640410;
CC P18206; Q6XVZ2: ipaA; Xeno; NbExp=4; IntAct=EBI-716775, EBI-7255868;
CC P18206; B0BXR4: RrIowa_0797; Xeno; NbExp=6; IntAct=EBI-716775, EBI-26356597;
CC P18206; Q62417-2: Sorbs1; Xeno; NbExp=3; IntAct=EBI-716775, EBI-7072893;
CC P18206-2; P56945: BCAR1; NbExp=3; IntAct=EBI-11027067, EBI-702093;
CC P18206-2; P35221: CTNNA1; NbExp=2; IntAct=EBI-11027067, EBI-701918;
CC P18206-2; P35637: FUS; NbExp=3; IntAct=EBI-11027067, EBI-400434;
CC P18206-2; O60711: LPXN; NbExp=3; IntAct=EBI-11027067, EBI-744222;
CC P18206-2; O76041: NEBL; NbExp=3; IntAct=EBI-11027067, EBI-2880203;
CC P18206-2; Q96CV9: OPTN; NbExp=3; IntAct=EBI-11027067, EBI-748974;
CC P18206-2; O60260-5: PRKN; NbExp=6; IntAct=EBI-11027067, EBI-21251460;
CC P18206-2; Q8IY67-1: RAVER1; NbExp=3; IntAct=EBI-11027067, EBI-15788272;
CC P18206-2; Q86UD0: SAPCD2; NbExp=3; IntAct=EBI-11027067, EBI-2561646;
CC P18206-2; O60504: SORBS3; NbExp=3; IntAct=EBI-11027067, EBI-741237;
CC P18206-2; P68135: ACTA1; Xeno; NbExp=2; IntAct=EBI-11027067, EBI-367540;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P12003};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P12003}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:P12003}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:P12003}. Cell junction, focal adhesion
CC {ECO:0000250|UniProtKB:P12003}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P85972}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:Q64727}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q64727}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q64727}. Note=Recruitment to cell-cell junctions
CC occurs in a myosin II-dependent manner. Interaction with CTNNB1 is
CC necessary for its localization to the cell-cell junctions.
CC {ECO:0000250|UniProtKB:P12003}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2; Synonyms=Metavinculin;
CC IsoId=P18206-1; Sequence=Displayed;
CC Name=1; Synonyms=Vinculin;
CC IsoId=P18206-2; Sequence=VSP_006731;
CC Name=3;
CC IsoId=P18206-3; Sequence=VSP_011857, VSP_011858, VSP_011859;
CC -!- TISSUE SPECIFICITY: Metavinculin is muscle-specific.
CC -!- DOMAIN: Exists in at least two conformations. When in the closed,
CC 'inactive' conformation, extensive interactions between the head and
CC tail domains prevent detectable binding to most of its ligands. It
CC takes on an 'active' conformation after cooperative and simultaneous
CC binding of two different ligands. This activation involves displacement
CC of the head-tail interactions and leads to a significant accumulation
CC of ternary complexes. The active form then binds a number of proteins
CC that have both signaling and structural roles that are essential for
CC cell adhesion. {ECO:0000269|PubMed:20484056}.
CC -!- DOMAIN: The N-terminal globular head (Vh) comprises of subdomains D1-
CC D4. The C-terminal tail (Vt) binds F-actin and cross-links actin
CC filaments into bundles. In isoform 2 (metavinculin) a 68 residue
CC insertion in the tail domain promotes actin severing instead of
CC bundling. An intramolecular interaction between Vh and Vt masks the F-
CC actin-binding domain located in Vt. The binding of talin and alpha-
CC actinin to the D1 subdomain of vinculin induces a helical bundle
CC conversion of this subdomain, leading to the disruption of the
CC intramolecular interaction and the exposure of the cryptic F-actin-
CC binding domain of Vt. Vt inhibits actin filament barbed end elongation
CC without affecting the critical concentration of actin assembly.
CC {ECO:0000269|PubMed:20484056}.
CC -!- PTM: Phosphorylated; on serines, threonines and tyrosines.
CC Phosphorylation on Tyr-1133 in activated platelets affects head-tail
CC interactions and cell spreading but has no effect on actin binding nor
CC on localization to focal adhesion plaques (By similarity).
CC {ECO:0000250|UniProtKB:P12003}.
CC -!- PTM: Acetylated; mainly by myristic acid but also by a small amount of
CC palmitic acid. {ECO:0000250|UniProtKB:P12003}.
CC -!- DISEASE: Cardiomyopathy, dilated 1W (CMD1W) [MIM:611407]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. {ECO:0000269|PubMed:11815424,
CC ECO:0000269|PubMed:16236538}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 15 (CMH15) [MIM:613255]:
CC A hereditary heart disorder characterized by ventricular hypertrophy,
CC which is usually asymmetric and often involves the interventricular
CC septum. The symptoms include dyspnea, syncope, collapse, palpitations,
CC and chest pain. They can be readily provoked by exercise. The disorder
CC has inter- and intrafamilial variability ranging from benign to
CC malignant forms with high risk of cardiac failure and sudden cardiac
CC death. {ECO:0000269|PubMed:16712796}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the vinculin/alpha-catenin family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Vinculin entry;
CC URL="https://en.wikipedia.org/wiki/Vinculin";
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DR EMBL; M33308; AAA61283.1; -; mRNA.
DR EMBL; BX537994; CAD97952.1; -; mRNA.
DR EMBL; AL596247; CAI13972.1; -; Genomic_DNA.
DR EMBL; AL731576; CAI13972.1; JOINED; Genomic_DNA.
DR EMBL; AL731576; CAI39673.1; -; Genomic_DNA.
DR EMBL; AL596247; CAI39673.1; JOINED; Genomic_DNA.
DR EMBL; BC039174; AAH39174.1; -; mRNA.
DR EMBL; L04933; AAA61271.1; -; Genomic_DNA.
DR EMBL; S87180; AAB21656.1; -; Genomic_DNA.
DR EMBL; S87175; AAB21656.1; JOINED; Genomic_DNA.
DR EMBL; S87178; AAB21656.1; JOINED; Genomic_DNA.
DR EMBL; S87223; AAB21657.1; -; Genomic_DNA.
DR EMBL; S87218; AAB21657.1; JOINED; Genomic_DNA.
DR CCDS; CCDS7340.1; -. [P18206-2]
DR CCDS; CCDS7341.1; -. [P18206-1]
DR PIR; A35955; A35955.
DR RefSeq; NP_003364.1; NM_003373.3. [P18206-2]
DR RefSeq; NP_054706.1; NM_014000.2. [P18206-1]
DR PDB; 1RKC; X-ray; 2.70 A; A=1-258.
DR PDB; 1RKE; X-ray; 2.35 A; A=1-258, B=882-1134.
DR PDB; 1SYQ; X-ray; 2.42 A; A=1-258.
DR PDB; 1TR2; X-ray; 2.90 A; A/B=1-1134.
DR PDB; 1YDI; X-ray; 1.80 A; A=1-258.
DR PDB; 2GWW; X-ray; 2.72 A; A=1-258.
DR PDB; 2HSQ; X-ray; 3.97 A; A=1-258.
DR PDB; 2IBF; X-ray; 3.20 A; A=1-258.
DR PDB; 3H2U; X-ray; 2.75 A; A/C=879-1134.
DR PDB; 3H2V; X-ray; 2.90 A; A/B/C/D=879-1134.
DR PDB; 3JBK; EM; 8.20 A; M=858-1129.
DR PDB; 3MYI; X-ray; 2.20 A; A=959-1130.
DR PDB; 3RF3; X-ray; 1.61 A; A/B=1-258.
DR PDB; 3S90; X-ray; 1.97 A; A/B=1-252.
DR PDB; 3TJ5; X-ray; 1.99 A; A=1-255.
DR PDB; 3TJ6; X-ray; 2.76 A; A=1-257.
DR PDB; 3VF0; X-ray; 2.54 A; A=856-1134.
DR PDB; 4DJ9; X-ray; 2.25 A; A=1-258.
DR PDB; 4EHP; X-ray; 2.66 A; A=1-252.
DR PDB; 4LN2; X-ray; 1.00 A; B=857-867.
DR PDB; 4LNP; X-ray; 1.41 A; B=870-879.
DR PDB; 4PR9; X-ray; 3.20 A; A/B/C/D/E/F=891-1134.
DR PDB; 5L0C; X-ray; 3.10 A; A/B/C/D=959-1134.
DR PDB; 5L0D; X-ray; 2.75 A; A/B/C/D=959-1130.
DR PDB; 5L0F; X-ray; 2.76 A; A/B=959-1134.
DR PDB; 5L0G; X-ray; 3.40 A; A/B/C/D=959-1134.
DR PDB; 5L0H; X-ray; 2.90 A; A=959-1134.
DR PDB; 5L0I; X-ray; 2.45 A; A=959-1134.
DR PDB; 5L0J; X-ray; 4.00 A; A/B=969-1134.
DR PDB; 5O2Q; NMR; -; A=854-870.
DR PDB; 6FUY; X-ray; 3.00 A; A=1-1134.
DR PDB; 6UPW; EM; 2.90 A; L/M=1-1134.
DR PDB; 7KTT; EM; 4.17 A; A=1-1134.
DR PDB; 7KTU; EM; 4.15 A; A=1-1134.
DR PDB; 7KTV; EM; 4.50 A; A=1-1134.
DR PDB; 7KTW; EM; 4.27 A; A=1-1134.
DR PDBsum; 1RKC; -.
DR PDBsum; 1RKE; -.
DR PDBsum; 1SYQ; -.
DR PDBsum; 1TR2; -.
DR PDBsum; 1YDI; -.
DR PDBsum; 2GWW; -.
DR PDBsum; 2HSQ; -.
DR PDBsum; 2IBF; -.
DR PDBsum; 3H2U; -.
DR PDBsum; 3H2V; -.
DR PDBsum; 3JBK; -.
DR PDBsum; 3MYI; -.
DR PDBsum; 3RF3; -.
DR PDBsum; 3S90; -.
DR PDBsum; 3TJ5; -.
DR PDBsum; 3TJ6; -.
DR PDBsum; 3VF0; -.
DR PDBsum; 4DJ9; -.
DR PDBsum; 4EHP; -.
DR PDBsum; 4LN2; -.
DR PDBsum; 4LNP; -.
DR PDBsum; 4PR9; -.
DR PDBsum; 5L0C; -.
DR PDBsum; 5L0D; -.
DR PDBsum; 5L0F; -.
DR PDBsum; 5L0G; -.
DR PDBsum; 5L0H; -.
DR PDBsum; 5L0I; -.
DR PDBsum; 5L0J; -.
DR PDBsum; 5O2Q; -.
DR PDBsum; 6FUY; -.
DR PDBsum; 6UPW; -.
DR PDBsum; 7KTT; -.
DR PDBsum; 7KTU; -.
DR PDBsum; 7KTV; -.
DR PDBsum; 7KTW; -.
DR AlphaFoldDB; P18206; -.
DR SMR; P18206; -.
DR BioGRID; 113257; 231.
DR ComplexPortal; CPX-791; Talin-1-Vinculin focal adhesion activation complex.
DR CORUM; P18206; -.
DR DIP; DIP-35570N; -.
DR ELM; P18206; -.
DR IntAct; P18206; 63.
DR MINT; P18206; -.
DR STRING; 9606.ENSP00000211998; -.
DR ChEMBL; CHEMBL4295723; -.
DR GlyGen; P18206; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P18206; -.
DR MetOSite; P18206; -.
DR PhosphoSitePlus; P18206; -.
DR SwissPalm; P18206; -.
DR BioMuta; VCL; -.
DR DMDM; 21903479; -.
DR DOSAC-COBS-2DPAGE; P18206; -.
DR OGP; P18206; -.
DR REPRODUCTION-2DPAGE; IPI00291175; -.
DR SWISS-2DPAGE; P18206; -.
DR UCD-2DPAGE; P18206; -.
DR EPD; P18206; -.
DR jPOST; P18206; -.
DR MassIVE; P18206; -.
DR MaxQB; P18206; -.
DR PaxDb; P18206; -.
DR PeptideAtlas; P18206; -.
DR PRIDE; P18206; -.
DR ProteomicsDB; 53553; -. [P18206-1]
DR ProteomicsDB; 53554; -. [P18206-2]
DR ProteomicsDB; 53555; -. [P18206-3]
DR Antibodypedia; 884; 930 antibodies from 45 providers.
DR DNASU; 7414; -.
DR Ensembl; ENST00000211998.10; ENSP00000211998.5; ENSG00000035403.18. [P18206-1]
DR Ensembl; ENST00000372755.7; ENSP00000361841.3; ENSG00000035403.18. [P18206-2]
DR GeneID; 7414; -.
DR KEGG; hsa:7414; -.
DR MANE-Select; ENST00000211998.10; ENSP00000211998.5; NM_014000.3; NP_054706.1.
DR UCSC; uc001jwe.4; human. [P18206-1]
DR CTD; 7414; -.
DR DisGeNET; 7414; -.
DR GeneCards; VCL; -.
DR GeneReviews; VCL; -.
DR HGNC; HGNC:12665; VCL.
DR HPA; ENSG00000035403; Low tissue specificity.
DR MalaCards; VCL; -.
DR MIM; 193065; gene.
DR MIM; 611407; phenotype.
DR MIM; 613255; phenotype.
DR neXtProt; NX_P18206; -.
DR OpenTargets; ENSG00000035403; -.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA37288; -.
DR VEuPathDB; HostDB:ENSG00000035403; -.
DR eggNOG; KOG3681; Eukaryota.
DR GeneTree; ENSGT01030000234543; -.
DR HOGENOM; CLU_012338_0_0_1; -.
DR InParanoid; P18206; -.
DR OMA; ANNLCEL; -.
DR PhylomeDB; P18206; -.
DR TreeFam; TF313686; -.
DR PathwayCommons; P18206; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-445355; Smooth Muscle Contraction.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR SignaLink; P18206; -.
DR SIGNOR; P18206; -.
DR BioGRID-ORCS; 7414; 118 hits in 1075 CRISPR screens.
DR ChiTaRS; VCL; human.
DR EvolutionaryTrace; P18206; -.
DR GeneWiki; Vinculin; -.
DR GenomeRNAi; 7414; -.
DR Pharos; P18206; Tbio.
DR PRO; PR:P18206; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P18206; protein.
DR Bgee; ENSG00000035403; Expressed in saphenous vein and 209 other tissues.
DR ExpressionAtlas; P18206; baseline and differential.
DR Genevisible; P18206; HS.
DR GO; GO:0005912; C:adherens junction; IDA:BHF-UCL.
DR GO; GO:0005903; C:brush border; ISS:AgBase.
DR GO; GO:0044291; C:cell-cell contact zone; IMP:ARUK-UCL.
DR GO; GO:0005911; C:cell-cell junction; IMP:ARUK-UCL.
DR GO; GO:0030055; C:cell-substrate junction; NAS:UniProtKB.
DR GO; GO:0043034; C:costamere; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0005916; C:fascia adherens; IEA:Ensembl.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; IDA:BHF-UCL.
DR GO; GO:0090637; C:inner dense plaque of desmosome; ISS:AgBase.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0090636; C:outer dense plaque of desmosome; ISS:AgBase.
DR GO; GO:0005886; C:plasma membrane; ISS:AgBase.
DR GO; GO:0002102; C:podosome; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; ISS:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:1990357; C:terminal web; ISS:AgBase.
DR GO; GO:0005915; C:zonula adherens; ISS:AgBase.
DR GO; GO:0003779; F:actin binding; IDA:BHF-UCL.
DR GO; GO:0045294; F:alpha-catenin binding; IPI:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; ISS:BHF-UCL.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0002162; F:dystroglycan binding; IPI:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0034333; P:adherens junction assembly; IMP:BHF-UCL.
DR GO; GO:0043297; P:apical junction assembly; IMP:UniProtKB.
DR GO; GO:0048675; P:axon extension; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0007160; P:cell-matrix adhesion; TAS:BHF-UCL.
DR GO; GO:0090136; P:epithelial cell-cell adhesion; IMP:BHF-UCL.
DR GO; GO:0030032; P:lamellipodium assembly; ISS:UniProtKB.
DR GO; GO:0035633; P:maintenance of blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IMP:BHF-UCL.
DR GO; GO:0030336; P:negative regulation of cell migration; TAS:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; HMP:UniProtKB.
DR GO; GO:0034394; P:protein localization to cell surface; IMP:BHF-UCL.
DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; IDA:ARUK-UCL.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; IMP:ARUK-UCL.
DR GO; GO:1904702; P:regulation of protein localization to adherens junction; IMP:ARUK-UCL.
DR DisProt; DP02858; -. [P18206-2]
DR InterPro; IPR036723; Alpha-catenin/vinculin-like_sf.
DR InterPro; IPR017997; Vinculin.
DR InterPro; IPR006077; Vinculin/catenin.
DR InterPro; IPR000633; Vinculin_CS.
DR PANTHER; PTHR46180; PTHR46180; 2.
DR Pfam; PF01044; Vinculin; 2.
DR SUPFAM; SSF47220; SSF47220; 6.
DR PROSITE; PS00663; VINCULIN_1; 1.
DR PROSITE; PS00664; VINCULIN_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative splicing;
KW Cardiomyopathy; Cell adhesion; Cell junction; Cell membrane; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Disease variant; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..1134
FT /note="Vinculin"
FT /id="PRO_0000064252"
FT REPEAT 259..369
FT /note="1"
FT /evidence="ECO:0000255"
FT REPEAT 370..479
FT /note="2"
FT /evidence="ECO:0000255"
FT REPEAT 480..589
FT /note="3"
FT /evidence="ECO:0000255"
FT REGION 1..835
FT /note="N-terminal globular head"
FT /evidence="ECO:0000269|PubMed:20484056"
FT REGION 168..208
FT /note="Talin-interaction"
FT /evidence="ECO:0000250|UniProtKB:P12003"
FT REGION 259..589
FT /note="3 X 112 AA tandem repeats"
FT /evidence="ECO:0000255"
FT REGION 741..764
FT /note="Interaction with ACTN4"
FT /evidence="ECO:0000269|PubMed:15988023,
FT ECO:0007744|PDB:1YDI"
FT REGION 836..878
FT /note="Linker (Pro-rich)"
FT /evidence="ECO:0000269|PubMed:20484056"
FT REGION 857..887
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 879..1134
FT /note="C-terminal tail"
FT /evidence="ECO:0000269|PubMed:20484056"
FT REGION 1003..1046
FT /note="Facilitates phospholipid membrane insertion"
FT /evidence="ECO:0000250|UniProtKB:Q64727"
FT REGION 1120..1134
FT /note="Facilitates phospholipid membrane insertion"
FT /evidence="ECO:0000250|UniProtKB:Q64727"
FT COMPBIAS 859..873
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P85972"
FT MOD_RES 173
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 260
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P85972"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 496
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 537
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES 574
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P85972"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 600
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 604
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 672
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 721
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 795
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 809
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 822
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1133
FT /note="Phosphotyrosine; by SRC-type Tyr-kinases"
FT /evidence="ECO:0000269|PubMed:15229287"
FT VAR_SEQ 1..73
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_011857"
FT VAR_SEQ 262..295
FT /note="DTEAMKRALASIDSKLNQAKGWLRDPSASPGDAG -> VRVLSGEISKIPNS
FT PWLGVLIGTCLILYLVIFVA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_011858"
FT VAR_SEQ 296..1134
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_011859"
FT VAR_SEQ 916..983
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:2116004"
FT /id="VSP_006731"
FT VARIANT 234
FT /note="V -> L (in dbSNP:rs17853882)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_037667"
FT VARIANT 277
FT /note="L -> M (in CMH15; dbSNP:rs71579353)"
FT /evidence="ECO:0000269|PubMed:16712796"
FT /id="VAR_035101"
FT VARIANT 934
FT /note="A -> V (in dbSNP:rs16931179)"
FT /evidence="ECO:0000269|PubMed:16236538"
FT /id="VAR_035102"
FT VARIANT 943
FT /note="P -> A (in dbSNP:rs71579375)"
FT /evidence="ECO:0000269|PubMed:16236538"
FT /id="VAR_035103"
FT VARIANT 954
FT /note="Missing (in CMD1W)"
FT /evidence="ECO:0000269|PubMed:11815424"
FT /id="VAR_035104"
FT VARIANT 975
FT /note="R -> W (in CMD1W; significantly alters metavinculin-
FT mediated cross-linking of actin filaments;
FT dbSNP:rs121917776)"
FT /evidence="ECO:0000269|PubMed:11815424,
FT ECO:0000269|PubMed:16236538"
FT /id="VAR_035105"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:4EHP"
FT HELIX 7..13
FT /evidence="ECO:0007829|PDB:3RF3"
FT HELIX 16..26
FT /evidence="ECO:0007829|PDB:3RF3"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:3RF3"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:1RKC"
FT HELIX 41..64
FT /evidence="ECO:0007829|PDB:3RF3"
FT HELIX 68..97
FT /evidence="ECO:0007829|PDB:3RF3"
FT HELIX 102..145
FT /evidence="ECO:0007829|PDB:3RF3"
FT HELIX 146..150
FT /evidence="ECO:0007829|PDB:3RF3"
FT HELIX 154..179
FT /evidence="ECO:0007829|PDB:3RF3"
FT HELIX 185..218
FT /evidence="ECO:0007829|PDB:3RF3"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:3TJ6"
FT HELIX 223..248
FT /evidence="ECO:0007829|PDB:3RF3"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:1YDI"
FT HELIX 258..274
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 277..284
FT /evidence="ECO:0007829|PDB:1TR2"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:6FUY"
FT HELIX 294..310
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 315..338
FT /evidence="ECO:0007829|PDB:1TR2"
FT TURN 339..342
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 347..351
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 353..393
FT /evidence="ECO:0007829|PDB:1TR2"
FT TURN 394..396
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 402..420
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 425..447
FT /evidence="ECO:0007829|PDB:1TR2"
FT TURN 448..450
FT /evidence="ECO:0007829|PDB:1TR2"
FT TURN 455..458
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 460..482
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 493..505
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 514..530
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 535..561
FT /evidence="ECO:0007829|PDB:1TR2"
FT STRAND 564..566
FT /evidence="ECO:0007829|PDB:6FUY"
FT HELIX 568..577
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 579..598
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 604..614
FT /evidence="ECO:0007829|PDB:1TR2"
FT TURN 620..624
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 625..650
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 655..681
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 690..714
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 719..743
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 746..772
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 777..792
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 794..806
FT /evidence="ECO:0007829|PDB:1TR2"
FT TURN 811..813
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 814..833
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 896..909
FT /evidence="ECO:0007829|PDB:1TR2"
FT HELIX 964..977
FT /evidence="ECO:0007829|PDB:3MYI"
FT HELIX 986..1005
FT /evidence="ECO:0007829|PDB:3MYI"
FT HELIX 1009..1011
FT /evidence="ECO:0007829|PDB:5L0F"
FT HELIX 1012..1037
FT /evidence="ECO:0007829|PDB:3MYI"
FT HELIX 1043..1053
FT /evidence="ECO:0007829|PDB:3MYI"
FT HELIX 1056..1072
FT /evidence="ECO:0007829|PDB:3MYI"
FT TURN 1073..1076
FT /evidence="ECO:0007829|PDB:3MYI"
FT STRAND 1077..1079
FT /evidence="ECO:0007829|PDB:3H2U"
FT HELIX 1081..1113
FT /evidence="ECO:0007829|PDB:3MYI"
FT STRAND 1114..1117
FT /evidence="ECO:0007829|PDB:3H2V"
FT TURN 1120..1122
FT /evidence="ECO:0007829|PDB:5L0F"
FT STRAND 1128..1130
FT /evidence="ECO:0007829|PDB:3VF0"
SQ SEQUENCE 1134 AA; 123799 MW; BFBD687DA836B0FA CRC64;
MPVFHTRTIE SILEPVAQQI SHLVIMHEEG EVDGKAIPDL TAPVAAVQAA VSNLVRVGKE
TVQTTEDQIL KRDMPPAFIK VENACTKLVQ AAQMLQSDPY SVPARDYLID GSRGILSGTS
DLLLTFDEAE VRKIIRVCKG ILEYLTVAEV VETMEDLVTY TKNLGPGMTK MAKMIDERQQ
ELTHQEHRVM LVNSMNTVKE LLPVLISAMK IFVTTKNSKN QGIEEALKNR NFTVEKMSAE
INEIIRVLQL TSWDEDAWAS KDTEAMKRAL ASIDSKLNQA KGWLRDPSAS PGDAGEQAIR
QILDEAGKVG ELCAGKERRE ILGTCKMLGQ MTDQVADLRA RGQGSSPVAM QKAQQVSQGL
DVLTAKVENA ARKLEAMTNS KQSIAKKIDA AQNWLADPNG GPEGEEQIRG ALAEARKIAE
LCDDPKERDD ILRSLGEISA LTSKLADLRR QGKGDSPEAR ALAKQVATAL QNLQTKTNRA
VANSRPAKAA VHLEGKIEQA QRWIDNPTVD DRGVGQAAIR GLVAEGHRLA NVMMGPYRQD
LLAKCDRVDQ LTAQLADLAA RGEGESPQAR ALASQLQDSL KDLKARMQEA MTQEVSDVFS
DTTTPIKLLA VAATAPPDAP NREEVFDERA ANFENHSGKL GATAEKAAAV GTANKSTVEG
IQASVKTARE LTPQVVSAAR ILLRNPGNQA AYEHFETMKN QWIDNVEKMT GLVDEAIDTK
SLLDASEEAI KKDLDKCKVA MANIQPQMLV AGATSIARRA NRILLVAKRE VENSEDPKFR
EAVKAASDEL SKTISPMVMD AKAVAGNISD PGLQKSFLDS GYRILGAVAK VREAFQPQEP
DFPPPPPDLE QLRLTDELAP PKPPLPEGEV PPPRPPPPEE KDEEFPEQKA GEVINQPMMM
AARQLHDEAR KWSSKPGIPA AEVGIGVVAE ADAADAAGFP VPPDMEDDYE PELLLMPSNQ
PVNQPILAAA QSLHREATKW SSKGNDIIAA AKRMALLMAE MSRLVRGGSG TKRALIQCAK
DIAKASDEVT RLAKEVAKQC TDKRIRTNLL QVCERIPTIS TQLKILSTVK ATMLGRTNIS
DEESEQATEM LVHNAQNLMQ SVKETVREAE AASIKIRTDA GFTLRWVRKT PWYQ
