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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 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. DR Genevisible; Q14315; HS. 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 //