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 27-MAR-2024, entry version 234.
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; Q6P050: FBXL22; NbExp=3; IntAct=EBI-489954, EBI-24224082;
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)
CC [MIM:617047]: 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:25351925}. Note=The disease
CC is caused by 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 PDB; 7OUU; X-ray; 1.47 A; A/B=1534-1736.
DR PDB; 7OUV; X-ray; 1.80 A; A/B=1534-1736.
DR PDB; 7P0E; X-ray; 1.60 A; A/B=1534-1736.
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 PDBsum; 7OUU; -.
DR PDBsum; 7OUV; -.
DR PDBsum; 7P0E; -.
DR SMR; Q14315; -.
DR BioGRID; 108607; 218.
DR DIP; DIP-33398N; -.
DR IntAct; Q14315; 89.
DR MINT; Q14315; -.
DR STRING; 9606.ENSP00000327145; -.
DR TCDB; 8.A.66.1.6; the dystrophin (dystrophin) family.
DR GlyCosmos; Q14315; 1 site, 1 glycan.
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; 9606-ENSP00000327145; -.
DR PeptideAtlas; Q14315; -.
DR ProteomicsDB; 59960; -. [Q14315-1]
DR ProteomicsDB; 59961; -. [Q14315-2]
DR Pumba; Q14315; -.
DR Antibodypedia; 1492; 183 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 AGR; HGNC:3756; -.
DR CTD; 2318; -.
DR DisGeNET; 2318; -.
DR GeneCards; FLNC; -.
DR HGNC; HGNC:3756; FLNC.
DR HPA; ENSG00000128591; Tissue enhanced (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 OrthoDB; 298396at2759; -.
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 1154 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 181 other cell types or 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:0045171; C:intercellular bridge; IDA:HPA.
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; cd21310; CH_FLNC_rpt1; 1.
DR CDD; cd21314; CH_FLNC_rpt2; 1.
DR CDD; cd00173; SH2; 1.
DR Gene3D; 1.10.418.10; Calponin-like domain; 2.
DR Gene3D; 2.60.40.10; Immunoglobulins; 24.
DR InterPro; IPR001589; Actinin_actin-bd_CS.
DR InterPro; IPR001715; CH_dom.
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; JITTERBUG, ISOFORM N; 1.
DR PANTHER; PTHR38537:SF17; JITTERBUG, ISOFORM N; 1.
DR Pfam; PF00307; CH; 2.
DR Pfam; PF00630; Filamin; 24.
DR SMART; SM00033; CH; 2.
DR SMART; SM00557; IG_FLMN; 24.
DR SUPFAM; SSF47576; Calponin-homology domain, CH-domain; 1.
DR SUPFAM; SSF81296; E set domains; 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; uncertain 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; dbSNP:rs1808925531)"
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; uncertain 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; uncertain significance; increased
FT aggregation; localized in perinuclear region of cytoplasm;
FT 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:rs767794768)"
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:7OUU"
FT STRAND 1543..1546
FT /evidence="ECO:0007829|PDB:7OUU"
FT HELIX 1547..1549
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1554..1558
FT /evidence="ECO:0007829|PDB:2D7M"
FT STRAND 1560..1565
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1569..1571
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1574..1579
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1589..1592
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1594..1602
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1606..1616
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1625..1631
FT /evidence="ECO:0007829|PDB:7OUU"
FT HELIX 1636..1638
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1640..1645
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1648..1653
FT /evidence="ECO:0007829|PDB:7OUV"
FT STRAND 1656..1659
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1664..1669
FT /evidence="ECO:0007829|PDB:7OUU"
FT TURN 1671..1673
FT /evidence="ECO:0007829|PDB:7P0E"
FT STRAND 1678..1683
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1689..1692
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1694..1696
FT /evidence="ECO:0007829|PDB:7P0E"
FT STRAND 1698..1706
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1710..1720
FT /evidence="ECO:0007829|PDB:7OUU"
FT STRAND 1729..1735
FT /evidence="ECO:0007829|PDB:7OUU"
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
//
