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FLNC_HUMAN
ID   FLNC_HUMAN              Reviewed;        2725 AA.
AC   Q14315; B2ZZ88; O95303; Q07985; Q9NS12; Q9NYE5; Q9UMR8; Q9Y503;
DT   16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT   28-JUL-2009, sequence version 3.
DT   03-AUG-2022, entry version 225.
DE   RecName: Full=Filamin-C;
DE            Short=FLN-C;
DE            Short=FLNc;
DE   AltName: Full=ABP-280-like protein;
DE   AltName: Full=ABP-L;
DE   AltName: Full=Actin-binding-like protein;
DE   AltName: Full=Filamin-2;
DE   AltName: Full=Gamma-filamin;
GN   Name=FLNC; Synonyms=ABPL, FLN2;
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), TISSUE SPECIFICITY, AND VARIANTS
RP   GLY-1580; ALA-1599 AND PRO-2203.
RC   TISSUE=Heart;
RX   PubMed=9791010; DOI=10.1006/bbrc.1998.9506;
RA   Xie Z.-W., Xu W.-F., Davie E.W., Chung D.W.;
RT   "Molecular cloning of human ABPL, an actin-binding protein homologue.";
RL   Biochem. Biophys. Res. Commun. 251:914-919(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), GENE ORGANIZATION, AND
RP   SIMILARITY TO OTHER MEMBERS OF THE FAMILY.
RX   PubMed=11153914; DOI=10.1007/s004390000414;
RA   Chakarova C., Wehnert M.S., Uhl K., Sakthivel S., Vosberg H.-P.,
RA   van der Ven P.F.M., Fuerst D.O.;
RT   "Genomic structure and fine mapping of the two human filamin gene
RT   paralogues FLNB and FLNC and comparative analysis of the filamin gene
RT   family.";
RL   Hum. Genet. 107:597-611(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS GLY-1580; ALA-1599;
RP   ARG-2135 AND PRO-2203.
RX   PubMed=10658210;
RX   DOI=10.1002/(sici)1097-0169(200002)45:2<149::aid-cm6>3.0.co;2-g;
RA   van der Ven P.F.M., Obermann W.M.J., Lemke B., Gautel M., Weber K.,
RA   Fuerst D.O.;
RT   "Characterization of muscle filamin isoforms suggests a possible role of
RT   gamma-filamin/ABP-L in sarcomeric Z-disc formation.";
RL   Cell Motil. Cytoskeleton 45:149-162(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH SGCD AND SGCG.
RC   TISSUE=Skeletal muscle;
RX   PubMed=10629222; DOI=10.1083/jcb.148.1.115;
RA   Thompson T.G., Chan Y.-M., Hack A.A., Brosius M., Rajala M., Lidov H.G.W.,
RA   McNally E.M., Watkins S., Kunkel L.M.;
RT   "Filamin 2 (FLN2): a muscle-specific sarcoglycan interacting protein.";
RL   J. Cell Biol. 148:115-126(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Kato S.;
RL   Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [7]
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   [8]
RP   PROTEIN SEQUENCE OF 70-81; 165-183; 335-343; 350-377; 422-437; 559-573;
RP   576-588; 718-727; 880-895; 900-911; 917-968; 978-991; 1015-1027; 1074-1088;
RP   1147-1157; 1242-1278; 1300-1313; 1355-1367; 1377-1394; 1475-1494;
RP   1568-1586; 1616-1627; 1658-1671; 1714-1719; 1809-1825; 1840-1860;
RP   1886-1901; 1932-1945; 1954-1968; 2000-2008; 2031-2043; 2050-2083;
RP   2114-2127; 2231-2291; 2294-2316; 2327-2356; 2411-2437; 2577-2589;
RP   2597-2616; 2642-2653 AND 2691-2699, PHOSPHORYLATION AT SER-2233, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Lung fibroblast;
RA   Bienvenut W.V., Pchelintsev N., Adams P.D.;
RL   Submitted (OCT-2009) to UniProtKB.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 585-815 AND 1638-2101 (ISOFORM 2), AND TISSUE
RP   SPECIFICITY.
RX   PubMed=7689010; DOI=10.1093/hmg/2.6.761;
RA   Maestrini E., Patrosso C., Mancini M., Rivella S., Rocchi M., Repetto M.,
RA   Villa A., Frattini A., Zoppe M., Vezzoni P., Toniolo D.;
RT   "Mapping of two genes encoding isoforms of the actin binding protein ABP-
RT   280, a dystrophin like protein, to Xq28 and to chromosome 7.";
RL   Hum. Mol. Genet. 2:761-766(1993).
RN   [10]
RP   INTERACTION WITH MYOZ1.
RX   PubMed=10984498; DOI=10.1074/jbc.m007493200;
RA   Faulkner G., Pallavicini A., Comelli A., Salamon M., Bortoletto G.,
RA   Ievolella C., Trevisan S., Kojic' S., Dalla Vecchia F., Laveder P.,
RA   Valle G., Lanfranchi G.;
RT   "FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-disc
RT   of skeletal muscle.";
RL   J. Biol. Chem. 275:41234-41242(2000).
RN   [11]
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, AND INTERACTION WITH
RP   MYOT.
RX   PubMed=11038172; DOI=10.1083/jcb.151.2.235;
RA   van der Ven P.F.M., Wiesner S., Salmikangas P., Auerbach D., Himmel M.,
RA   Kempa S., Hayess K., Pacholsky D., Taivainen A., Schroeder R., Carpen O.,
RA   Fuerst D.O.;
RT   "Indications for a novel muscular dystrophy pathway: gamma-filamin, the
RT   muscle-specific filamin isoform, interacts with myotilin.";
RL   J. Cell Biol. 151:235-248(2000).
RN   [12]
RP   INTERACTION WITH KCND2.
RX   PubMed=11102480; DOI=10.1523/jneurosci.20-23-08736.2000;
RA   Petrecca K., Miller D.M., Shrier A.;
RT   "Localization and enhanced current density of the Kv4.2 potassium channel
RT   by interaction with the actin-binding protein filamin.";
RL   J. Neurosci. 20:8736-8744(2000).
RN   [13]
RP   INTERACTION WITH MYOZ1.
RX   PubMed=11171996; DOI=10.1073/pnas.98.4.1595;
RA   Takada F., Vander Woude D.L., Tong H.-Q., Thompson T.G., Watkins S.C.,
RA   Kunkel L.M., Beggs A.H.;
RT   "Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal
RT   muscle Z lines.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:1595-1600(2001).
RN   [14]
RP   INTERACTION WITH INPPL1.
RX   PubMed=11739414; DOI=10.1083/jcb.200104005;
RA   Dyson J.M., O'Malley C.J., Becanovic J., Munday A.D., Berndt M.C.,
RA   Coghill I.D., Nandurkar H.H., Ooms L.M., Mitchell C.A.;
RT   "The SH2-containing inositol polyphosphate 5-phosphatase, SHIP-2, binds
RT   filamin and regulates submembraneous actin.";
RL   J. Cell Biol. 155:1065-1079(2001).
RN   [15]
RP   REVIEW.
RX   PubMed=11252955; DOI=10.1038/35052082;
RA   Stossel T.P., Condeelis J., Cooley L., Hartwig J.H., Noegel A.,
RA   Schleicher M., Shapiro S.S.;
RT   "Filamins as integrators of cell mechanics and signalling.";
RL   Nat. Rev. Mol. Cell Biol. 2:138-145(2001).
RN   [16]
RP   SILENCING IN CANCER CELL LINES MKN28 AND MKN74.
RX   PubMed=12438262;
RA   Kaneda A., Kaminishi M., Yanagihara K., Sugimura T., Ushijima T.;
RT   "Identification of silencing of nine genes in human gastric cancers.";
RL   Cancer Res. 62:6645-6650(2002).
RN   [17]
RP   INTERACTION WITH MYOZ3.
RX   PubMed=11842093; DOI=10.1074/jbc.m200712200;
RA   Frey N., Olson E.N.;
RT   "Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin
RT   family, interacts with multiple Z-disc proteins.";
RL   J. Biol. Chem. 277:13998-14004(2002).
RN   [18]
RP   DIMERIZATION, AND INTERACTION WITH FLNB.
RX   PubMed=12525170; DOI=10.1021/bi026501+;
RA   Himmel M., van der Ven P.F.M., Stoecklein W., Fuerst D.O.;
RT   "The limits of promiscuity: isoform-specific dimerization of filamins.";
RL   Biochemistry 42:430-439(2003).
RN   [19]
RP   INVOLVEMENT IN MFM5.
RX   PubMed=15929027; DOI=10.1086/431959;
RA   Vorgerd M., van der Ven P.F.M., Bruchertseifer V., Loewe T., Kley R.A.,
RA   Schroeder R., Lochmueller H., Himmel M., Koehler K., Fuerst D.O.,
RA   Huebner A.;
RT   "A mutation in the dimerization domain of filamin C causes a novel type of
RT   autosomal dominant myofibrillar myopathy.";
RL   Am. J. Hum. Genet. 77:297-304(2005).
RN   [20]
RP   INTERACTION WITH ITGB1; MYOT AND MYOZ1.
RX   PubMed=16076904; DOI=10.1242/jcs.02484;
RA   Gontier Y., Taivainen A., Fontao L., Sonnenberg A., van der Flier A.,
RA   Carpen O., Faulkner G., Borradori L.;
RT   "The Z-disc proteins myotilin and FATZ-1 interact with each other and are
RT   connected to the sarcolemma via muscle-specific filamins.";
RL   J. Cell Sci. 118:3739-3749(2005).
RN   [21]
RP   INTERACTION WITH USP25.
RX   PubMed=16501887; DOI=10.1007/s00018-005-5533-1;
RA   Bosch-Comas A., Lindsten K., Gonzalez-Duarte R., Masucci M.G., Marfany G.;
RT   "The ubiquitin-specific protease USP25 interacts with three sarcomeric
RT   proteins.";
RL   Cell. Mol. Life Sci. 63:723-734(2006).
RN   [22]
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   [23]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1161, AND IDENTIFICATION BY
RP   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   [24]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2233, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [25]
RP   INTERACTION WITH SYNPO2.
RX   PubMed=20554076; DOI=10.1016/j.ejcb.2010.04.004;
RA   Linnemann A., van der Ven P.F., Vakeel P., Albinus B., Simonis D.,
RA   Bendas G., Schenk J.A., Micheel B., Kley R.A., Fuerst D.O.;
RT   "The sarcomeric Z-disc component myopodin is a multiadapter protein that
RT   interacts with filamin and alpha-actinin.";
RL   Eur. J. Cell Biol. 89:681-692(2010).
RN   [26]
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   [27]
RP   INTERACTION WITH ANK3.
RX   PubMed=21223964; DOI=10.1016/j.yexcr.2011.01.002;
RA   Maiweilidan Y., Klauza I., Kordeli E.;
RT   "Novel interactions of ankyrins-G at the costameres: the muscle-specific
RT   Obscurin/Titin-Binding-related Domain (OTBD) binds plectin and filamin C.";
RL   Exp. Cell Res. 317:724-736(2011).
RN   [28]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2233, AND IDENTIFICATION BY
RP   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   [29]
RP   UBIQUITINATION BY FBXL22.
RX   PubMed=22972877; DOI=10.1161/circresaha.112.271007;
RA   Spaich S., Will R.D., Just S., Spaich S., Kuhn C., Frank D., Berger I.M.,
RA   Wiemann S., Korn B., Koegl M., Backs J., Katus H.A., Rottbauer W., Frey N.;
RT   "F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box
RT   protein that regulates sarcomeric protein turnover and is essential for
RT   maintenance of contractile function in vivo.";
RL   Circ. Res. 111:1504-1516(2012).
RN   [30]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-2042; SER-2233;
RP   SER-2236; THR-2238; SER-2586; SER-2617; SER-2620; SER-2623; SER-2632;
RP   SER-2714 AND SER-2718, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=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   [31]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1338 AND SER-2233, AND
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   [32]
RP   FUNCTION, CHARACTERIZATION OF VARIANT SER-1674, AND MUTAGENESIS OF
RP   1668-VAL--GLY-1674.
RX   PubMed=34405687; DOI=10.1161/circresaha.120.317076;
RA   Agarwal R., Paulo J.A., Toepfer C.N., Ewoldt J.K., Sundaram S., Chopra A.,
RA   Zhang Q., Gorham J., DePalma S.R., Chen C.S., Gygi S.P., Seidman C.E.,
RA   Seidman J.G.;
RT   "Filamin C cardiomyopathy variants cause protein and lysosome
RT   accumulation.";
RL   Circ. Res. 129:751-766(2021).
RN   [33]
RP   X-RAY CRYSTALLOGRAPHY (1.43 ANGSTROMS) OF 2633-2725, AND MUTAGENESIS OF
RP   MET-2669.
RX   PubMed=15642266; DOI=10.1016/j.str.2004.10.014;
RA   Pudas R., Kiema T.-R., Butler P.J.G., Stewart M., Ylaenne J.;
RT   "Structural basis for vertebrate filamin dimerization.";
RL   Structure 13:111-119(2005).
RN   [34]
RP   STRUCTURE BY NMR OF 1536-2599.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of the filamin domains from human filamin C.";
RL   Submitted (NOV-2006) to the PDB data bank.
RN   [35]
RP   X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 2495-2598, AND SUBUNIT.
RX   PubMed=17379241; DOI=10.1016/j.jmb.2007.02.018;
RA   Sjekloca L., Pudas R., Sjoblom B., Konarev P., Carugo O., Rybin V.,
RA   Kiema T.R., Svergun D., Ylanne J., Djinovic Carugo K.;
RT   "Crystal structure of human filamin C domain 23 and small angle scattering
RT   model for filamin C 23-24 dimer.";
RL   J. Mol. Biol. 368:1011-1023(2007).
RN   [36]
RP   STRUCTURE BY NMR OF 2302-2415 IN COMPLEX WITH FBLIM1.
RX   PubMed=19074766; DOI=10.1074/jbc.m807719200;
RA   Ithychanda S.S., Das M., Ma Y.Q., Ding K., Wang X., Gupta S., Wu C.,
RA   Plow E.F., Qin J.;
RT   "Migfilin, a molecular switch in regulation of integrin activation.";
RL   J. Biol. Chem. 284:4713-4722(2009).
RN   [37]
RP   VARIANTS MPD4 THR-193 AND THR-251, AND CHARACTERIZATION OF VARIANTS MPD4
RP   THR-193 AND THR-251.
RX   PubMed=21620354; DOI=10.1016/j.ajhg.2011.04.021;
RA   Duff R.M., Tay V., Hackman P., Ravenscroft G., McLean C., Kennedy P.,
RA   Steinbach A., Schoffler W., van der Ven P.F., Furst D.O., Song J.,
RA   Djinovic-Carugo K., Penttila S., Raheem O., Reardon K., Malandrini A.,
RA   Gambelli S., Villanova M., Nowak K.J., Williams D.R., Landers J.E.,
RA   Brown R.H. Jr., Udd B., Laing N.G.;
RT   "Mutations in the N-terminal actin-binding domain of filamin C cause a
RT   distal myopathy.";
RL   Am. J. Hum. Genet. 88:729-740(2011).
RN   [38]
RP   INVOLVEMENT IN CMH26, VARIANTS CMH26 ALA-123; LYS-290; THR-1539; HIS-2133;
RP   SER-2151 AND VAL-2430, CHARACTERIZATION OF VARIANTS CMH26 ALA-123;
RP   THR-1539; HIS-2133 AND VAL-2430, AND SUBCELLULAR LOCATION.
RX   PubMed=25351925; DOI=10.1038/ncomms6326;
RA   Valdes-Mas R., Gutierrez-Fernandez A., Gomez J., Coto E., Astudillo A.,
RA   Puente D.A., Reguero J.R., Alvarez V., Moris C., Leon D., Martin M.,
RA   Puente X.S., Lopez-Otin C.;
RT   "Mutations in filamin C cause a new form of familial hypertrophic
RT   cardiomyopathy.";
RL   Nat. Commun. 5:5326-5326(2014).
RN   [39]
RP   INVOLVEMENT IN RCM5, VARIANTS RCM5 LEU-1624 AND PHE-2160, AND
RP   CHARACTERIZATION OF VARIANT RCM5 LEU-1624.
RX   PubMed=26666891; DOI=10.1002/humu.22942;
RG   FORGE Canada Consortium;
RA   Brodehl A., Ferrier R.A., Hamilton S.J., Greenway S.C., Brundler M.A.,
RA   Yu W., Gibson W.T., McKinnon M.L., McGillivray B., Alvarez N., Giuffre M.,
RA   Schwartzentruber J., Gerull B.;
RT   "Mutations in FLNC are Associated with Familial Restrictive
RT   Cardiomyopathy.";
RL   Hum. Mutat. 37:269-279(2016).
CC   -!- FUNCTION: Muscle-specific filamin, which plays a central role in
CC       sarcomere assembly and organization (PubMed:34405687). Critical for
CC       normal myogenesis, it probably functions as a large actin-cross-linking
CC       protein with structural functions at the Z lines in muscle cells. May
CC       be involved in reorganizing the actin cytoskeleton in response to
CC       signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6,
CC       ECO:0000269|PubMed:34405687}.
CC   -!- SUBUNIT: Homodimer; the filamin repeat 24 and the second hinge domain
CC       are important for dimer formation. Interacts with FLNB, INPPL1, ITGB1A,
CC       KCND2, MYOT, MYOZ1 and MYOZ3. Interacts with sarcoglycans SGCD and
CC       SGCG. Interacts (via filament repeats 17-18, 20-21 and 24) with USP25
CC       (isoform USP25m only). Interacts with FBLIM1. Interacts with XIRP1;
CC       this interaction is mediated by filamin 20 repeat. Interacts with KY.
CC       Interacts with IGFN1 (By similarity). Interacts with MICALL2 (By
CC       similarity). Interacts with ANK3. Interacts with SYNPO2. {ECO:0000250,
CC       ECO:0000269|PubMed:10629222, ECO:0000269|PubMed:10984498,
CC       ECO:0000269|PubMed:11038172, ECO:0000269|PubMed:11102480,
CC       ECO:0000269|PubMed:11171996, ECO:0000269|PubMed:11739414,
CC       ECO:0000269|PubMed:11842093, ECO:0000269|PubMed:12525170,
CC       ECO:0000269|PubMed:16076904, ECO:0000269|PubMed:16501887,
CC       ECO:0000269|PubMed:16631741, ECO:0000269|PubMed:17379241,
CC       ECO:0000269|PubMed:19074766, ECO:0000269|PubMed:20554076,
CC       ECO:0000269|PubMed:21223964}.
CC   -!- INTERACTION:
CC       Q14315; P00519: ABL1; NbExp=2; IntAct=EBI-489954, EBI-375543;
CC       Q14315; P46108: CRK; NbExp=2; IntAct=EBI-489954, EBI-886;
CC       Q14315; P62993: GRB2; NbExp=2; IntAct=EBI-489954, EBI-401755;
CC       Q14315; Q9UBF9: MYOT; NbExp=6; IntAct=EBI-489954, EBI-296701;
CC       Q14315; Q702N8: XIRP1; NbExp=4; IntAct=EBI-489954, EBI-7851194;
CC       Q14315; O70511-7: Ank3; Xeno; NbExp=2; IntAct=EBI-489954, EBI-9663485;
CC       Q14315-1; Q14315-1: FLNC; NbExp=3; IntAct=EBI-15532913, EBI-15532913;
CC       Q14315-1; Q9ERP3: Trim54; Xeno; NbExp=2; IntAct=EBI-15532913, EBI-15626796;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11038172,
CC       ECO:0000269|PubMed:25351925}. Membrane {ECO:0000269|PubMed:11038172};
CC       Peripheral membrane protein {ECO:0000269|PubMed:11038172}. Cytoplasm,
CC       cytoskeleton {ECO:0000269|PubMed:11038172}. Cytoplasm, myofibril,
CC       sarcomere, Z line {ECO:0000269|PubMed:11038172}. Note=A small amount
CC       localizes at membranes. In striated muscle cells, it predominantly
CC       localizes in myofibrillar Z lines, while a minor fraction localizes
CC       with subsarcolemme. Targeting to developing and mature Z lines is
CC       mediated by the intradomain insert.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q14315-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q14315-2; Sequence=VSP_007579;
CC   -!- TISSUE SPECIFICITY: Highly expressed in striated muscles. Weakly
CC       expressed in thyroid, fetal brain, fetal lung, retina, spinal cord and
CC       bone marrow. Not expressed in testis, pancreas, adrenal gland,
CC       placenta, liver and kidney. {ECO:0000269|PubMed:11038172,
CC       ECO:0000269|PubMed:7689010, ECO:0000269|PubMed:9791010}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in both differentiating and adult
CC       muscles.
CC   -!- PTM: Ubiquitinated by FBXL22, leading to proteasomal degradation.
CC       {ECO:0000269|PubMed:22972877}.
CC   -!- DISEASE: Myopathy, myofibrillar, 5 (MFM5) [MIM:609524]: A form of
CC       myofibrillar myopathy, a group of chronic neuromuscular disorders
CC       characterized at ultrastructural level by disintegration of the
CC       sarcomeric Z disk and myofibrils, and replacement of the normal
CC       myofibrillar markings by small dense granules, or larger hyaline
CC       masses, or amorphous material. MFM5 is characterized by onset in
CC       adulthood, clinical features of a limb-girdle myopathy, and focal
CC       myofibrillar destruction. {ECO:0000269|PubMed:15929027}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Myopathy, distal, 4 (MPD4) [MIM:614065]: A slowly progressive
CC       muscular disorder characterized by distal muscle weakness and atrophy
CC       affecting the upper and lower limbs. Onset occurs around the third to
CC       fourth decades of life, and patients remain ambulatory even after long
CC       disease duration. Muscle biopsy shows non-specific changes with no
CC       evidence of rods, necrosis, or inflammation.
CC       {ECO:0000269|PubMed:21620354}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Cardiomyopathy, familial hypertrophic 26 (CMH26) [MIM:617047]:
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:25351925}. Note=The disease is caused by
CC       variants affecting the gene represented in this entry.
CC   -!- DISEASE: Cardiomyopathy, familial restrictive 5 (RCM5) [MIM:617047]: A
CC       heart disorder characterized by impaired filling of the ventricles with
CC       reduced diastolic volume, in the presence of normal or near normal wall
CC       thickness and systolic function. {ECO:0000269|PubMed:26666891}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- MISCELLANEOUS: Silenced in MKN28 and MKN74 gastric cancer cell lines
CC       due to aberrant methylation of the gene.
CC   -!- SIMILARITY: Belongs to the filamin family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAD12245.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAF68195.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAF80245.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=CAA49688.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF089841; AAD12245.1; ALT_INIT; mRNA.
DR   EMBL; AF184126; AAF68195.1; ALT_INIT; Genomic_DNA.
DR   EMBL; AF184119; AAF68195.1; JOINED; Genomic_DNA.
DR   EMBL; AF184120; AAF68195.1; JOINED; Genomic_DNA.
DR   EMBL; AF184121; AAF68195.1; JOINED; Genomic_DNA.
DR   EMBL; AF184122; AAF68195.1; JOINED; Genomic_DNA.
DR   EMBL; AF184123; AAF68195.1; JOINED; Genomic_DNA.
DR   EMBL; AF184124; AAF68195.1; JOINED; Genomic_DNA.
DR   EMBL; AF184125; AAF68195.1; JOINED; Genomic_DNA.
DR   EMBL; AF252549; AAF67190.1; -; Genomic_DNA.
DR   EMBL; AJ132990; CAB51535.1; -; Genomic_DNA.
DR   EMBL; AJ012737; CAB46442.1; -; mRNA.
DR   EMBL; AB371585; BAG48314.1; -; mRNA.
DR   EMBL; AC025594; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471070; EAW83691.1; -; Genomic_DNA.
DR   EMBL; AF146692; AAF80245.1; ALT_FRAME; mRNA.
DR   EMBL; X70083; CAA49688.1; ALT_FRAME; mRNA.
DR   EMBL; X70084; CAA49689.1; -; mRNA.
DR   CCDS; CCDS43644.1; -. [Q14315-1]
DR   CCDS; CCDS47705.1; -. [Q14315-2]
DR   PIR; S37775; S37775.
DR   PIR; S37778; S37778.
DR   RefSeq; NP_001120959.1; NM_001127487.1. [Q14315-2]
DR   RefSeq; NP_001449.3; NM_001458.4. [Q14315-1]
DR   PDB; 1V05; X-ray; 1.43 A; A=2633-2725.
DR   PDB; 2D7M; NMR; -; A=1536-1637.
DR   PDB; 2D7N; NMR; -; A=1782-1861.
DR   PDB; 2D7O; NMR; -; A=1856-1953.
DR   PDB; 2D7P; NMR; -; A=2405-2503.
DR   PDB; 2D7Q; NMR; -; A=2502-2599.
DR   PDB; 2K9U; NMR; -; A=2302-2415.
DR   PDB; 2NQC; X-ray; 2.05 A; A=2495-2598.
DR   PDB; 3V8O; X-ray; 2.80 A; A/B=569-761.
DR   PDB; 4MGX; X-ray; 3.16 A; A=572-756.
DR   PDBsum; 1V05; -.
DR   PDBsum; 2D7M; -.
DR   PDBsum; 2D7N; -.
DR   PDBsum; 2D7O; -.
DR   PDBsum; 2D7P; -.
DR   PDBsum; 2D7Q; -.
DR   PDBsum; 2K9U; -.
DR   PDBsum; 2NQC; -.
DR   PDBsum; 3V8O; -.
DR   PDBsum; 4MGX; -.
DR   SMR; Q14315; -.
DR   BioGRID; 108607; 156.
DR   DIP; DIP-33398N; -.
DR   IntAct; Q14315; 87.
DR   MINT; Q14315; -.
DR   STRING; 9606.ENSP00000327145; -.
DR   TCDB; 8.A.66.1.6; the dystrophin (dystrophin) family.
DR   GlyGen; Q14315; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q14315; -.
DR   MetOSite; Q14315; -.
DR   PhosphoSitePlus; Q14315; -.
DR   SwissPalm; Q14315; -.
DR   BioMuta; FLNC; -.
DR   DMDM; 254763419; -.
DR   EPD; Q14315; -.
DR   jPOST; Q14315; -.
DR   MassIVE; Q14315; -.
DR   MaxQB; Q14315; -.
DR   PaxDb; Q14315; -.
DR   PeptideAtlas; Q14315; -.
DR   PRIDE; Q14315; -.
DR   ProteomicsDB; 59960; -. [Q14315-1]
DR   ProteomicsDB; 59961; -. [Q14315-2]
DR   Antibodypedia; 1492; 150 antibodies from 20 providers.
DR   DNASU; 2318; -.
DR   Ensembl; ENST00000325888.13; ENSP00000327145.8; ENSG00000128591.16. [Q14315-1]
DR   Ensembl; ENST00000346177.6; ENSP00000344002.6; ENSG00000128591.16. [Q14315-2]
DR   GeneID; 2318; -.
DR   KEGG; hsa:2318; -.
DR   MANE-Select; ENST00000325888.13; ENSP00000327145.8; NM_001458.5; NP_001449.3.
DR   UCSC; uc003vnz.5; human. [Q14315-1]
DR   CTD; 2318; -.
DR   DisGeNET; 2318; -.
DR   GeneCards; FLNC; -.
DR   HGNC; HGNC:3756; FLNC.
DR   HPA; ENSG00000128591; Group enriched (heart muscle, skeletal muscle, tongue).
DR   MalaCards; FLNC; -.
DR   MIM; 102565; gene.
DR   MIM; 609524; phenotype.
DR   MIM; 614065; phenotype.
DR   MIM; 617047; phenotype.
DR   neXtProt; NX_Q14315; -.
DR   OpenTargets; ENSG00000128591; -.
DR   Orphanet; 63273; Distal myopathy with posterior leg and anterior hand involvement.
DR   Orphanet; 75249; Familial isolated restrictive cardiomyopathy.
DR   Orphanet; 171445; Muscle filaminopathy.
DR   Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR   PharmGKB; PA28174; -.
DR   VEuPathDB; HostDB:ENSG00000128591; -.
DR   eggNOG; KOG0518; Eukaryota.
DR   GeneTree; ENSGT00940000153588; -.
DR   HOGENOM; CLU_000783_0_0_1; -.
DR   InParanoid; Q14315; -.
DR   OMA; YPVMAGK; -.
DR   PhylomeDB; Q14315; -.
DR   TreeFam; TF313685; -.
DR   PathwayCommons; Q14315; -.
DR   Reactome; R-HSA-446353; Cell-extracellular matrix interactions.
DR   SignaLink; Q14315; -.
DR   SIGNOR; Q14315; -.
DR   BioGRID-ORCS; 2318; 11 hits in 1076 CRISPR screens.
DR   ChiTaRS; FLNC; human.
DR   EvolutionaryTrace; Q14315; -.
DR   GeneWiki; FLNC_(gene); -.
DR   GenomeRNAi; 2318; -.
DR   Pharos; Q14315; Tbio.
DR   PRO; PR:Q14315; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q14315; protein.
DR   Bgee; ENSG00000128591; Expressed in gastrocnemius and 179 other tissues.
DR   Genevisible; Q14315; HS.
DR   GO; GO:0043034; C:costamere; TAS:BHF-UCL.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL.
DR   GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR   GO; GO:0051015; F:actin filament binding; IEA:InterPro.
DR   GO; GO:0030506; F:ankyrin binding; IPI:BHF-UCL.
DR   GO; GO:0008092; F:cytoskeletal protein binding; IPI:AgBase.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0045214; P:sarcomere organization; IMP:UniProtKB.
DR   CDD; cd00014; CH; 2.
DR   Gene3D; 1.10.418.10; -; 2.
DR   Gene3D; 2.60.40.10; -; 24.
DR   InterPro; IPR001589; Actinin_actin-bd_CS.
DR   InterPro; IPR001715; CH-domain.
DR   InterPro; IPR036872; CH_dom_sf.
DR   InterPro; IPR044801; Filamin.
DR   InterPro; IPR017868; Filamin/ABP280_repeat-like.
DR   InterPro; IPR001298; Filamin/ABP280_rpt.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR014756; Ig_E-set.
DR   PANTHER; PTHR38537; PTHR38537; 2.
DR   Pfam; PF00307; CH; 2.
DR   Pfam; PF00630; Filamin; 23.
DR   SMART; SM00033; CH; 2.
DR   SMART; SM00557; IG_FLMN; 24.
DR   SUPFAM; SSF47576; SSF47576; 1.
DR   SUPFAM; SSF81296; SSF81296; 24.
DR   PROSITE; PS00019; ACTININ_1; 1.
DR   PROSITE; PS00020; ACTININ_2; 1.
DR   PROSITE; PS50021; CH; 2.
DR   PROSITE; PS50194; FILAMIN_REPEAT; 24.
PE   1: Evidence at protein level;
KW   3D-structure; Actin-binding; Alternative splicing; Cardiomyopathy;
KW   Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease variant;
KW   Membrane; Methylation; Myofibrillar myopathy; Phosphoprotein;
KW   Reference proteome; Repeat; Ubl conjugation.
FT   CHAIN           1..2725
FT                   /note="Filamin-C"
FT                   /id="PRO_0000087301"
FT   DOMAIN          36..142
FT                   /note="Calponin-homology (CH) 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT   DOMAIN          159..262
FT                   /note="Calponin-homology (CH) 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT   REPEAT          270..368
FT                   /note="Filamin 1"
FT   REPEAT          370..468
FT                   /note="Filamin 2"
FT   REPEAT          469..565
FT                   /note="Filamin 3"
FT   REPEAT          566..658
FT                   /note="Filamin 4"
FT   REPEAT          662..758
FT                   /note="Filamin 5"
FT   REPEAT          759..861
FT                   /note="Filamin 6"
FT   REPEAT          862..960
FT                   /note="Filamin 7"
FT   REPEAT          961..1056
FT                   /note="Filamin 8"
FT   REPEAT          1057..1149
FT                   /note="Filamin 9"
FT   REPEAT          1150..1244
FT                   /note="Filamin 10"
FT   REPEAT          1245..1344
FT                   /note="Filamin 11"
FT   REPEAT          1345..1437
FT                   /note="Filamin 12"
FT   REPEAT          1438..1533
FT                   /note="Filamin 13"
FT   REPEAT          1534..1630
FT                   /note="Filamin 14"
FT   REPEAT          1635..1734
FT                   /note="Filamin 15"
FT   REPEAT          1759..1853
FT                   /note="Filamin 16"
FT   REPEAT          1854..1946
FT                   /note="Filamin 17"
FT   REPEAT          1947..2033
FT                   /note="Filamin 18"
FT   REPEAT          2036..2128
FT                   /note="Filamin 19"
FT   REPEAT          2244..2306
FT                   /note="Filamin 20; mediates interaction with XIRP1"
FT   REPEAT          2309..2401
FT                   /note="Filamin 21"
FT   REPEAT          2403..2496
FT                   /note="Filamin 22"
FT   REPEAT          2500..2592
FT                   /note="Filamin 23"
FT   REPEAT          2630..2724
FT                   /note="Filamin 24"
FT   REGION          1..259
FT                   /note="Actin-binding"
FT   REGION          1..28
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1735..1758
FT                   /note="Hinge 1"
FT   REGION          1740..1765
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2162..2243
FT                   /note="Intradomain insert; mediate targeting to Z lines"
FT   REGION          2240..2260
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2403..2724
FT                   /note="Interaction with INPPL1"
FT                   /evidence="ECO:0000269|PubMed:11739414"
FT   REGION          2593..2725
FT                   /note="Self-association site, tail"
FT                   /evidence="ECO:0000250"
FT   REGION          2593..2629
FT                   /note="Hinge 2"
FT   COMPBIAS        2240..2258
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         5
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1002
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8VHX6"
FT   MOD_RES         1161
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18088087"
FT   MOD_RES         1338
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         2042
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         2233
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19369195,
FT                   ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT                   ECO:0007744|PubMed:24275569"
FT   MOD_RES         2236
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         2238
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         2586
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         2617
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         2620
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         2623
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         2632
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         2714
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         2718
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         1734..1766
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10629222,
FT                   ECO:0000303|PubMed:10658210, ECO:0000303|PubMed:7689010"
FT                   /id="VSP_007579"
FT   VARIANT         123
FT                   /note="V -> A (in CMH26; increased aggregation; localized
FT                   in perinuclear region of cytoplasm; dbSNP:rs1562991002)"
FT                   /evidence="ECO:0000269|PubMed:25351925"
FT                   /id="VAR_077036"
FT   VARIANT         193
FT                   /note="A -> T (in MPD4; results in slightly decreased
FT                   thermal stability and increased actin-binding activity;
FT                   results in significantly decreased nuclear localization
FT                   with formation of intracellular protein aggregates;
FT                   dbSNP:rs387906587)"
FT                   /evidence="ECO:0000269|PubMed:21620354"
FT                   /id="VAR_066212"
FT   VARIANT         251
FT                   /note="M -> T (in MPD4; results in slightly decreased
FT                   thermal stability and increased actin-binding activity;
FT                   results in the formation of intracellular protein
FT                   aggregates; dbSNP:rs387906586)"
FT                   /evidence="ECO:0000269|PubMed:21620354"
FT                   /id="VAR_066213"
FT   VARIANT         290
FT                   /note="N -> K (in CMH26; unknown pathological
FT                   significance)"
FT                   /evidence="ECO:0000269|PubMed:25351925"
FT                   /id="VAR_077037"
FT   VARIANT         1539
FT                   /note="A -> T (in CMH26; increased actin aggregation;
FT                   localized in perinuclear region of cytoplasm;
FT                   dbSNP:rs1562999443)"
FT                   /evidence="ECO:0000269|PubMed:25351925"
FT                   /id="VAR_077038"
FT   VARIANT         1567
FT                   /note="R -> Q (in dbSNP:rs2291569)"
FT                   /id="VAR_015705"
FT   VARIANT         1580
FT                   /note="D -> G (in dbSNP:rs2643766)"
FT                   /evidence="ECO:0000269|PubMed:10658210,
FT                   ECO:0000269|PubMed:9791010"
FT                   /id="VAR_015706"
FT   VARIANT         1599
FT                   /note="T -> A (in dbSNP:rs2643767)"
FT                   /evidence="ECO:0000269|PubMed:10658210,
FT                   ECO:0000269|PubMed:9791010"
FT                   /id="VAR_015707"
FT   VARIANT         1624
FT                   /note="S -> L (in RCM5; increased protein aggregates;
FT                   effect on cytoplasm localization; localized in perinuclear
FT                   region of cytoplasm; no effect on expression;
FT                   dbSNP:rs879255639)"
FT                   /evidence="ECO:0000269|PubMed:26666891"
FT                   /id="VAR_077039"
FT   VARIANT         1674
FT                   /note="G -> S (does not affect sarcomere structure or
FT                   contractile performance in mutant induced pluripotent stem
FT                   cell-derived cardiomyocytes; dbSNP:rs374124083)"
FT                   /evidence="ECO:0000269|PubMed:34405687"
FT                   /id="VAR_085683"
FT   VARIANT         2133
FT                   /note="R -> H (in CMH26; increased aggregation; localized
FT                   in perinuclear region of cytoplasm)"
FT                   /evidence="ECO:0000269|PubMed:25351925"
FT                   /id="VAR_077040"
FT   VARIANT         2135
FT                   /note="K -> R (in dbSNP:rs1063261)"
FT                   /evidence="ECO:0000269|PubMed:10658210"
FT                   /id="VAR_015708"
FT   VARIANT         2151
FT                   /note="G -> S (in CMH26; unknown pathological
FT                   significance)"
FT                   /evidence="ECO:0000269|PubMed:25351925"
FT                   /id="VAR_077041"
FT   VARIANT         2160
FT                   /note="I -> F (in RCM5; no effect on cytoplasm
FT                   localization; no effect on expression; dbSNP:rs879255640)"
FT                   /evidence="ECO:0000269|PubMed:26666891"
FT                   /id="VAR_077042"
FT   VARIANT         2203
FT                   /note="R -> P (in dbSNP:rs1063262)"
FT                   /evidence="ECO:0000269|PubMed:10658210,
FT                   ECO:0000269|PubMed:9791010"
FT                   /id="VAR_015709"
FT   VARIANT         2430
FT                   /note="A -> V (in CMH26; unknown pathological significance;
FT                   increased aggregation; localized in perinuclear region of
FT                   cytoplasm; dbSNP:rs200516164)"
FT                   /evidence="ECO:0000269|PubMed:25351925"
FT                   /id="VAR_077043"
FT   VARIANT         2626
FT                   /note="S -> N (in dbSNP:rs2639142)"
FT                   /id="VAR_015710"
FT   VARIANT         2637
FT                   /note="K -> Q (in dbSNP:rs2291572)"
FT                   /id="VAR_015711"
FT   MUTAGEN         1668..1674
FT                   /note="Missing: No effect on sarcomere structure or
FT                   contractile performance in mutant induced pluripotent stem
FT                   cell-derived cardiomyocytes."
FT                   /evidence="ECO:0000269|PubMed:34405687"
FT   MUTAGEN         2669
FT                   /note="M->D: Abolishes dimerization."
FT                   /evidence="ECO:0000269|PubMed:15642266"
FT   CONFLICT        138
FT                   /note="I -> T (in Ref. 3; CAB46442)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        189
FT                   /note="K -> E (in Ref. 3; CAB46442)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        194
FT                   /note="L -> Q (in Ref. 3; CAB46442)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        218
FT                   /note="A -> S (in Ref. 1; AAD12245 and 2; AAF68195)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        233
FT                   /note="Q -> L (in Ref. 3; CAB46442)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        484
FT                   /note="L -> P (in Ref. 3; CAB46442)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        585
FT                   /note="Q -> V (in Ref. 9; CAA49688)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        723
FT                   /note="D -> N (in Ref. 1; AAD12245, 2; AAF68195 and 9;
FT                   CAA49688)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1091
FT                   /note="G -> D (in Ref. 3; CAB46442)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1640
FT                   /note="L -> T (in Ref. 9; CAA49689)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1668
FT                   /note="V -> M (in Ref. 3; CAB46442)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2101
FT                   /note="C -> S (in Ref. 3; CAB46442 and 9; CAA49689)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2321..2322
FT                   /note="GT -> RA (in Ref. 1; AAD12245 and 2; AAF68195)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2355
FT                   /note="S -> N (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2382
FT                   /note="E -> K (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2484
FT                   /note="G -> C (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2491
FT                   /note="P -> L (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2499
FT                   /note="Q -> H (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2514
FT                   /note="G -> E (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2528..2530
FT                   /note="VNT -> DDH (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2535
FT                   /note="S -> F (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2547
FT                   /note="K -> N (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2557
FT                   /note="E -> G (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2601..2602
FT                   /note="HS -> QH (in Ref. 4; AAF80245)"
FT                   /evidence="ECO:0000305"
FT   STRAND          574..578
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   HELIX           579..581
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          583..585
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          590..599
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   HELIX           601..603
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          604..612
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          617..620
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          622..630
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          636..644
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          653..659
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   HELIX           667..669
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          671..674
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   HELIX           675..677
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          678..680
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          688..693
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          697..699
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          702..708
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          717..720
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          722..730
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          734..744
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   STRAND          753..759
FT                   /evidence="ECO:0007829|PDB:3V8O"
FT   HELIX           1539..1541
FT                   /evidence="ECO:0007829|PDB:2D7M"
FT   STRAND          1542..1547
FT                   /evidence="ECO:0007829|PDB:2D7M"
FT   STRAND          1554..1558
FT                   /evidence="ECO:0007829|PDB:2D7M"
FT   STRAND          1560..1569
FT                   /evidence="ECO:0007829|PDB:2D7M"
FT   STRAND          1574..1579
FT                   /evidence="ECO:0007829|PDB:2D7M"
FT   STRAND          1588..1592
FT                   /evidence="ECO:0007829|PDB:2D7M"
FT   STRAND          1594..1596
FT                   /evidence="ECO:0007829|PDB:2D7M"
FT   STRAND          1598..1602
FT                   /evidence="ECO:0007829|PDB:2D7M"
FT   STRAND          1608..1618
FT                   /evidence="ECO:0007829|PDB:2D7M"
FT   STRAND          1625..1631
FT                   /evidence="ECO:0007829|PDB:2D7M"
FT   STRAND          1785..1789
FT                   /evidence="ECO:0007829|PDB:2D7N"
FT   STRAND          1794..1796
FT                   /evidence="ECO:0007829|PDB:2D7N"
FT   STRAND          1798..1803
FT                   /evidence="ECO:0007829|PDB:2D7N"
FT   STRAND          1813..1816
FT                   /evidence="ECO:0007829|PDB:2D7N"
FT   STRAND          1818..1820
FT                   /evidence="ECO:0007829|PDB:2D7N"
FT   STRAND          1822..1826
FT                   /evidence="ECO:0007829|PDB:2D7N"
FT   STRAND          1832..1843
FT                   /evidence="ECO:0007829|PDB:2D7N"
FT   STRAND          1849..1854
FT                   /evidence="ECO:0007829|PDB:2D7N"
FT   STRAND          1863..1866
FT                   /evidence="ECO:0007829|PDB:2D7O"
FT   HELIX           1867..1870
FT                   /evidence="ECO:0007829|PDB:2D7O"
FT   STRAND          1871..1873
FT                   /evidence="ECO:0007829|PDB:2D7O"
FT   STRAND          1878..1883
FT                   /evidence="ECO:0007829|PDB:2D7O"
FT   TURN            1885..1887
FT                   /evidence="ECO:0007829|PDB:2D7O"
FT   STRAND          1895..1900
FT                   /evidence="ECO:0007829|PDB:2D7O"
FT   STRAND          1910..1918
FT                   /evidence="ECO:0007829|PDB:2D7O"
FT   STRAND          1924..1929
FT                   /evidence="ECO:0007829|PDB:2D7O"
FT   STRAND          1931..1934
FT                   /evidence="ECO:0007829|PDB:2D7O"
FT   STRAND          1941..1947
FT                   /evidence="ECO:0007829|PDB:2D7O"
FT   STRAND          2303..2308
FT                   /evidence="ECO:0007829|PDB:2K9U"
FT   TURN            2313..2316
FT                   /evidence="ECO:0007829|PDB:2K9U"
FT   STRAND          2318..2322
FT                   /evidence="ECO:0007829|PDB:2K9U"
FT   TURN            2323..2325
FT                   /evidence="ECO:0007829|PDB:2K9U"
FT   STRAND          2332..2338
FT                   /evidence="ECO:0007829|PDB:2K9U"
FT   STRAND          2344..2355
FT                   /evidence="ECO:0007829|PDB:2K9U"
FT   STRAND          2358..2362
FT                   /evidence="ECO:0007829|PDB:2K9U"
FT   STRAND          2365..2374
FT                   /evidence="ECO:0007829|PDB:2K9U"
FT   STRAND          2377..2389
FT                   /evidence="ECO:0007829|PDB:2K9U"
FT   STRAND          2396..2404
FT                   /evidence="ECO:0007829|PDB:2K9U"
FT   HELIX           2407..2410
FT                   /evidence="ECO:0007829|PDB:2D7P"
FT   STRAND          2427..2432
FT                   /evidence="ECO:0007829|PDB:2D7P"
FT   STRAND          2440..2445
FT                   /evidence="ECO:0007829|PDB:2D7P"
FT   STRAND          2447..2449
FT                   /evidence="ECO:0007829|PDB:2D7P"
FT   STRAND          2463..2468
FT                   /evidence="ECO:0007829|PDB:2D7P"
FT   STRAND          2474..2484
FT                   /evidence="ECO:0007829|PDB:2D7P"
FT   STRAND          2491..2496
FT                   /evidence="ECO:0007829|PDB:2D7P"
FT   HELIX           2505..2507
FT                   /evidence="ECO:0007829|PDB:2NQC"
FT   STRAND          2509..2512
FT                   /evidence="ECO:0007829|PDB:2NQC"
FT   HELIX           2513..2515
FT                   /evidence="ECO:0007829|PDB:2NQC"
FT   STRAND          2517..2519
FT                   /evidence="ECO:0007829|PDB:2NQC"
FT   STRAND          2524..2529
FT                   /evidence="ECO:0007829|PDB:2NQC"
FT   TURN            2531..2533
FT                   /evidence="ECO:0007829|PDB:2D7Q"
FT   STRAND          2538..2546
FT                   /evidence="ECO:0007829|PDB:2NQC"
FT   STRAND          2549..2555
FT                   /evidence="ECO:0007829|PDB:2NQC"
FT   STRAND          2558..2564
FT                   /evidence="ECO:0007829|PDB:2NQC"
FT   STRAND          2569..2580
FT                   /evidence="ECO:0007829|PDB:2NQC"
FT   STRAND          2587..2594
FT                   /evidence="ECO:0007829|PDB:2NQC"
FT   HELIX           2635..2637
FT                   /evidence="ECO:0007829|PDB:1V05"
FT   STRAND          2639..2642
FT                   /evidence="ECO:0007829|PDB:1V05"
FT   HELIX           2643..2645
FT                   /evidence="ECO:0007829|PDB:1V05"
FT   STRAND          2654..2659
FT                   /evidence="ECO:0007829|PDB:1V05"
FT   STRAND          2663..2665
FT                   /evidence="ECO:0007829|PDB:1V05"
FT   STRAND          2668..2673
FT                   /evidence="ECO:0007829|PDB:1V05"
FT   STRAND          2675..2677
FT                   /evidence="ECO:0007829|PDB:1V05"
FT   STRAND          2680..2686
FT                   /evidence="ECO:0007829|PDB:1V05"
FT   STRAND          2691..2697
FT                   /evidence="ECO:0007829|PDB:1V05"
FT   STRAND          2702..2710
FT                   /evidence="ECO:0007829|PDB:1V05"
FT   STRAND          2719..2724
FT                   /evidence="ECO:0007829|PDB:1V05"
SQ   SEQUENCE   2725 AA;  291022 MW;  B7C8516C2366E75D CRC64;
     MMNNSGYSDA GLGLGDETDE MPSTEKDLAE DAPWKKIQQN TFTRWCNEHL KCVGKRLTDL
     QRDLSDGLRL IALLEVLSQK RMYRKFHPRP NFRQMKLENV SVALEFLERE HIKLVSIDSK
     AIVDGNLKLI LGLIWTLILH YSISMPMWED EDDEDARKQT PKQRLLGWIQ NKVPQLPITN
     FNRDWQDGKA LGALVDNCAP GLCPDWEAWD PNQPVENARE AMQQADDWLG VPQVIAPEEI
     VDPNVDEHSV MTYLSQFPKA KLKPGAPVRS KQLNPKKAIA YGPGIEPQGN TVLQPAHFTV
     QTVDAGVGEV LVYIEDPEGH TEEAKVVPNN DKDRTYAVSY VPKVAGLHKV TVLFAGQNIE
     RSPFEVNVGM ALGDANKVSA RGPGLEPVGN VANKPTYFDI YTAGAGTGDV AVVIVDPQGR
     RDTVEVALED KGDSTFRCTY RPAMEGPHTV HVAFAGAPIT RSPFPVHVSE ACNPNACRAS
     GRGLQPKGVR VKEVADFKVF TKGAGSGELK VTVKGPKGTE EPVKVREAGD GVFECEYYPV
     VPGKYVVTIT WGGYAIPRSP FEVQVSPEAG VQKVRAWGPG LETGQVGKSA DFVVEAIGTE
     VGTLGFSIEG PSQAKIECDD KGDGSCDVRY WPTEPGEYAV HVICDDEDIR DSPFIAHILP
     APPDCFPDKV KAFGPGLEPT GCIVDKPAEF TIDARAAGKG DLKLYAQDAD GCPIDIKVIP
     NGDGTFRCSY VPTKPIKHTI IISWGGVNVP KSPFRVNVGE GSHPERVKVY GPGVEKTGLK
     ANEPTYFTVD CSEAGQGDVS IGIKCAPGVV GPAEADIDFD IIKNDNDTFT VKYTPPGAGR
     YTIMVLFANQ EIPASPFHIK VDPSHDASKV KAEGPGLNRT GVEVGKPTHF TVLTKGAGKA
     KLDVQFAGTA KGEVVRDFEI IDNHDYSYTV KYTAVQQGNM AVTVTYGGDP VPKSPFVVNV
     APPLDLSKIK VQGLNSKVAV GQEQAFSVNT RGAGGQGQLD VRMTSPSRRP IPCKLEPGGG
     AEAQAVRYMP PEEGPYKVDI TYDGHPVPGS PFAVEGVLPP DPSKVCAYGP GLKGGLVGTP
     APFSIDTKGA GTGGLGLTVE GPCEAKIECQ DNGDGSCAVS YLPTEPGEYT INILFAEAHI
     PGSPFKATIR PVFDPSKVRA SGPGLERGKV GEAATFTVDC SEAGEAELTI EILSDAGVKA
     EVLIHNNADG TYHITYSPAF PGTYTITIKY GGHPVPKFPT RVHVQPAVDT SGVKVSGPGV
     EPHGVLREVT TEFTVDARSL TATGGNHVTA RVLNPSGAKT DTYVTDNGDG TYRVQYTAYE
     EGVHLVEVLY DEVAVPKSPF RVGVTEGCDP TRVRAFGPGL EGGLVNKANR FTVETRGAGT
     GGLGLAIEGP SEAKMSCKDN KDGSCTVEYI PFTPGDYDVN ITFGGRPIPG SPFRVPVKDV
     VDPGKVKCSG PGLGAGVRAR VPQTFTVDCS QAGRAPLQVA VLGPTGVAEP VEVRDNGDGT
     HTVHYTPATD GPYTVAVKYA DQEVPRSPFK IKVLPAHDAS KVRASGPGLN ASGIPASLPV
     EFTIDARDAG EGLLTVQILD PEGKPKKANI RDNGDGTYTV SYLPDMSGRY TITIKYGGDE
     IPYSPFRIHA LPTGDASKCL VTVSIGGHGL GACLGPRIQI GQETVITVDA KAAGEGKVTC
     TVSTPDGAEL DVDVVENHDG TFDIYYTAPE PGKYVITIRF GGEHIPNSPF HVLACDPLPH
     EEEPSEVPQL RQPYAPPRPG ARPTHWATEE PVVPVEPMES MLRPFNLVIP FAVQKGELTG
     EVRMPSGKTA RPNITDNKDG TITVRYAPTE KGLHQMGIKY DGNHIPGSPL QFYVDAINSR
     HVSAYGPGLS HGMVNKPATF TIVTKDAGEG GLSLAVEGPS KAEITCKDNK DGTCTVSYLP
     TAPGDYSIIV RFDDKHIPGS PFTAKITGDD SMRTSQLNVG TSTDVSLKIT ESDLSQLTAS
     IRAPSGNEEP CLLKRLPNRH IGISFTPKEV GEHVVSVRKS GKHVTNSPFK ILVGPSEIGD
     ASKVRVWGKG LSEGHTFQVA EFIVDTRNAG YGGLGLSIEG PSKVDINCED MEDGTCKVTY
     CPTEPGTYII NIKFADKHVP GSPFTVKVTG EGRMKESITR RRQAPSIATI GSTCDLNLKI
     PGNWFQMVSA QERLTRTFTR SSHTYTRTER TEISKTRGGE TKREVRVEES TQVGGDPFPA
     VFGDFLGRER LGSFGSITRQ QEGEASSQDM TAQVTSPSGK VEAAEIVEGE DSAYSVRFVP
     QEMGPHTVAV KYRGQHVPGS PFQFTVGPLG EGGAHKVRAG GTGLERGVAG VPAEFSIWTR
     EAGAGGLSIA VEGPSKAEIA FEDRKDGSCG VSYVVQEPGD YEVSIKFNDE HIPDSPFVVP
     VASLSDDARR LTVTSLQETG LKVNQPASFA VQLNGARGVI DARVHTPSGA VEECYVSELD
     SDKHTIRFIP HENGVHSIDV KFNGAHIPGS PFKIRVGEQS QAGDPGLVSA YGPGLEGGTT
     GVSSEFIVNT LNAGSGALSV TIDGPSKVQL DCRECPEGHV VTYTPMAPGN YLIAIKYGGP
     QHIVGSPFKA KVTGPRLSGG HSLHETSTVL VETVTKSSSS RGSSYSSIPK FSSDASKVVT
     RGPGLSQAFV GQKNSFTVDC SKAGTNMMMV GVHGPKTPCE EVYVKHMGNR VYNVTYTVKE
     KGDYILIVKW GDESVPGSPF KVKVP
 
 
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