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 27-MAR-2024, entry version 244. 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 INTERACTION WITH S.FLEXNERI ICSA (MICROBIAL INFECTION). RX PubMed=8702989; DOI=10.1074/jbc.271.36.21878; RA Suzuki T., Saga S., Sasakawa C.; RT "Functional analysis of Shigella VirG domains essential for interaction RT with vinculin and actin-based motility."; RL J. Biol. Chem. 271:21878-21885(1996). RN [10] 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 [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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 [29] 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 [30] 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 -!- SUBUNIT: (Microbial infection) Interacts via its globular head domain CC with the central portion of S.flexneri IcsA (also called VirG). CC {ECO:0000269|PubMed:8702989}. 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}. Cell projection, podosome 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) CC [MIM:613255]: A hereditary heart disorder characterized by ventricular CC hypertrophy, which is usually asymmetric and often involves the CC interventricular septum. The symptoms include dyspnea, syncope, CC collapse, palpitations, and chest pain. They can be readily provoked by CC exercise. The disorder has inter- and intrafamilial variability ranging CC from benign to malignant forms with high risk of cardiac failure and CC sudden cardiac death. {ECO:0000269|PubMed:16712796}. Note=The disease CC is caused by 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-20844; -. DR EMDB; EMD-23029; -. DR EMDB; EMD-23030; -. DR EMDB; EMD-23031; -. DR EMDB; EMD-23032; -. DR EMDB; EMD-6447; -. DR SMR; P18206; -. DR BioGRID; 113257; 269. DR ComplexPortal; CPX-791; Talin-1-Vinculin focal adhesion activation complex. DR CORUM; P18206; -. DR DIP; DIP-35570N; -. DR ELM; P18206; -. DR IntAct; P18206; 68. 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 EPD; P18206; -. DR jPOST; P18206; -. DR MassIVE; P18206; -. DR MaxQB; P18206; -. DR PaxDb; 9606-ENSP00000211998; -. DR PeptideAtlas; P18206; -. DR ProteomicsDB; 53553; -. [P18206-1] DR ProteomicsDB; 53554; -. [P18206-2] DR ProteomicsDB; 53555; -. [P18206-3] DR Pumba; P18206; -. DR Antibodypedia; 884; 1088 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 AGR; HGNC:12665; -. 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 OrthoDB; 2908505at2759; -. 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; 122 hits in 1153 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 211 other cell types or tissues. DR ExpressionAtlas; P18206; baseline and differential. DR GO; GO:0005912; C:adherens junction; IDA:BHF-UCL. DR GO; GO:0005903; C:brush border; ISS:AgBase. DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW. 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:0061826; C:podosome ring; 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:0060090; F:molecular adaptor activity; EXP:DisProt. 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 Gene3D; 1.20.120.230; Alpha-catenin/vinculin-like; 2. DR Gene3D; 1.20.120.810; Vinculin, Vh2 four-helix bundle; 3. 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; VINCULIN; 1. DR PANTHER; PTHR46180:SF1; VINCULIN; 1. DR Pfam; PF01044; Vinculin; 2. DR PRINTS; PR00806; VINCULIN. DR SUPFAM; SSF47220; alpha-catenin/vinculin-like; 6. DR PROSITE; PS00663; VINCULIN_1; 1. DR PROSITE; PS00664; VINCULIN_2; 3. DR SWISS-2DPAGE; P18206; -. DR UCD-2DPAGE; P18206; -. DR Genevisible; P18206; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Actin-binding; Alternative splicing; KW Cardiomyopathy; Cell adhesion; Cell junction; Cell membrane; KW Cell projection; Cytoplasm; Cytoskeleton; Direct protein sequencing; KW Disease variant; Lipoprotein; Membrane; Palmitate; Phosphoprotein; KW 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 FT metavinculin-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 //