MYPC3_HUMAN
ID MYPC3_HUMAN Reviewed; 1274 AA.
AC Q14896; A5PL00; Q16410; Q6R2F7; Q9UE27; Q9UM53;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 4.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Myosin-binding protein C, cardiac-type;
DE Short=Cardiac MyBP-C;
DE AltName: Full=C-protein, cardiac muscle isoform;
GN Name=MYBPC3;
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], AND VARIANT CMH4 GLN-820.
RC TISSUE=Heart;
RX PubMed=7744002; DOI=10.1002/j.1460-2075.1995.tb07187.x;
RA Gautel M., Zuffardi O., Freiburg A., Labeit S.;
RT "Phosphorylation switches specific for the cardiac isoform of myosin
RT binding protein-C: a modulator of cardiac contraction?";
RL EMBO J. 14:1952-1960(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CMH4 GLN-542 AND GLN-820.
RX PubMed=9048664; DOI=10.1161/01.res.0000435859.24609.b3;
RA Carrier L., Bonne G., Bahrend E., Yu B., Richard P., Niel F., Hainque B.,
RA Cruaud C., Gary F., Labeit S., Bouhour J.-B., Dubourg O., Desnos M.,
RA Hagege A.A., Trent R.J., Komajda M., Fiszman M., Schwartz K.;
RT "Organization and sequence of human cardiac myosin binding protein C gene
RT (MYBPC3) and identification of mutations predicted to produce truncated
RT proteins in familial hypertrophic cardiomyopathy.";
RL Circ. Res. 80:427-434(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CMH4 GLN-451; GLN-495 AND
RP GLN-502.
RX PubMed=9562578; DOI=10.1056/nejm199804303381802;
RA Niimura H., Bachinski L.L., Sangwatanaroj S., Watkins H., Chudley A.E.,
RA McKenna W., Kristinsson A., Roberts R., Sole M., Maron B.J., Seidman J.G.,
RA Seidman C.E.;
RT "Mutations in the gene for cardiac myosin-binding protein C and late-onset
RT familial hypertrophic cardiomyopathy.";
RL N. Engl. J. Med. 338:1248-1257(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-158; ILE-189; GLY-236;
RP GLN-281; TRP-382; VAL-383; THR-522; VAL-833; GLU-998 AND CYS-1048.
RG NIEHS SNPs program;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Rieder M.J., Bertucci C., Stanaway I.B., Johnson E.J., Swanson J.E.,
RA Siegel D.L., da Ponte S.H., Igartua C., Patterson K., Nickerson D.A.;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 640-694.
RX PubMed=7493026; DOI=10.1038/ng1295-438;
RA Bonne G., Carrier L., Bercovici J., Cruaud C., Richard P., Hainque B.,
RA Gautel M., Labeit S., James M., Beckmann J., Weissenbach J., Vosberg H.-P.,
RA Fiszman M., Komajda M., Schwartz K.;
RT "Cardiac myosin binding protein-C gene splice acceptor site mutation is
RT associated with familial hypertrophic cardiomyopathy.";
RL Nat. Genet. 11:438-440(1995).
RN [9]
RP STRUCTURE BY NMR OF 641-770, AND CHARACTERIZATION OF VARIANTS HIS-654 AND
RP LYS-755.
RX PubMed=12787675; DOI=10.1016/s0022-2836(03)00425-x;
RA Idowu S.M., Gautel M., Perkins S.J., Pfuhl M.;
RT "Structure, stability and dynamics of the central domain of cardiac myosin
RT binding protein C (MyBP-C): implications for multidomain assembly and
RT causes for cardiomyopathy.";
RL J. Mol. Biol. 329:745-761(2003).
RN [10]
RP STRUCTURE BY NMR OF 358-450, AND DISULFIDE BOND.
RX PubMed=15213454; DOI=10.1023/b:jnmr.0000032510.03606.63;
RA Ababou A., Zhou L., Gautel M., Pfuhl M.;
RT "Sequence specific assignment of domain C1 of the N-terminal myosin-binding
RT site of human cardiac myosin binding protein C (MyBP-C).";
RL J. Biomol. NMR 29:431-432(2004).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 151-258.
RX PubMed=18560154; DOI=10.1107/s0907444908008792;
RA Fisher S.J., Helliwell J.R., Khurshid S., Govada L., Redwood C.,
RA Squire J.M., Chayen N.E.;
RT "An investigation into the protonation states of the C1 domain of cardiac
RT myosin-binding protein C.";
RL Acta Crystallogr. D 64:658-664(2008).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 151-258.
RX PubMed=18374358; DOI=10.1016/j.jmb.2008.02.044;
RA Govada L., Carpenter L., da Fonseca P.C., Helliwell J.R., Rizkallah P.,
RA Flashman E., Chayen N.E., Redwood C., Squire J.M.;
RT "Crystal structure of the C1 domain of cardiac myosin binding protein-C:
RT implications for hypertrophic cardiomyopathy.";
RL J. Mol. Biol. 378:387-397(2008).
RN [13]
RP STRUCTURE BY NMR OF 151-260, AND ZINC-BINDING SITE.
RX PubMed=18926831; DOI=10.1016/j.jmb.2008.09.065;
RA Ababou A., Rostkova E., Mistry S., Le Masurier C., Gautel M., Pfuhl M.;
RT "Myosin binding protein C positioned to play a key role in regulation of
RT muscle contraction: structure and interactions of domain C1.";
RL J. Mol. Biol. 384:615-630(2008).
RN [14]
RP VARIANT CMH4 LYS-755.
RX PubMed=9541104; DOI=10.1136/jmg.35.3.205;
RA Yu B., French J.A., Carrier L., Jeremy R.W., McTaggart D.R.,
RA Nicholson M.R., Hambly B., Semsarian C., Richmond D.R., Schwartz K.,
RA Trent R.J.;
RT "Molecular pathology of familial hypertrophic cardiomyopathy caused by
RT mutations in the cardiac myosin binding protein C gene.";
RL J. Med. Genet. 35:205-210(1998).
RN [15]
RP VARIANT CMH4 HIS-654.
RX PubMed=9541115; DOI=10.1136/jmg.35.3.253;
RA Moolman-Smook J.C., Mayosi B., Brink P., Corfield V.A.;
RT "Identification of a new missense mutation in MyBP-C associated with
RT hypertrophic cardiomyopathy.";
RL J. Med. Genet. 35:253-254(1998).
RN [16]
RP VARIANT MET-896.
RX PubMed=10521296; DOI=10.1086/302623;
RA Moolman-Smook J.C., De Lange W.J., Bruwer E.C.D., Brink P.A.,
RA Corfield V.A.;
RT "The origins of hypertrophic cardiomyopathy-causing mutations in two South
RT African subpopulations: a unique profile of both independent and founder
RT events.";
RL Am. J. Hum. Genet. 65:1308-1320(1999).
RN [17]
RP VARIANT CMH4 GLN-495, AND VARIANT GLN-326.
RX PubMed=11499718; DOI=10.1016/s0735-1097(01)01386-9;
RA Maron B.J., Niimura H., Casey S.A., Soper M.K., Wright G.B., Seidman J.G.,
RA Seidman C.E.;
RT "Development of left ventricular hypertrophy in adults in hypertrophic
RT cardiomyopathy caused by cardiac myosin-binding protein C gene mutations.";
RL J. Am. Coll. Cardiol. 38:315-321(2001).
RN [18]
RP VARIANTS CMH4 TRP-282; ARG-507; ARG-566 AND ILE-1115.
RX PubMed=11499719; DOI=10.1016/s0735-1097(01)01387-0;
RA Erdmann J., Raible J., Maki-Abadi J., Hummel M., Hammann J., Wollnik B.,
RA Frantz E., Fleck E., Hetzer R., Regitz-Zagrosek V.;
RT "Spectrum of clinical phenotypes and gene variants in cardiac myosin-
RT binding protein C mutation carriers with hypertrophic cardiomyopathy.";
RL J. Am. Coll. Cardiol. 38:322-330(2001).
RN [19]
RP VARIANT CMH4 THR-948, AND VARIANTS GLY-236 AND GLN-326.
RX PubMed=12379228; DOI=10.1016/s0006-291x(02)02374-4;
RA Daehmlow S., Erdmann J., Knueppel T., Gille C., Froemmel C., Hummel M.,
RA Hetzer R., Regitz-Zagrosek V.;
RT "Novel mutations in sarcomeric protein genes in dilated cardiomyopathy.";
RL Biochem. Biophys. Res. Commun. 298:116-120(2002).
RN [20]
RP VARIANTS CMH4 ALA-59 AND GLN-1002, AND VARIANT GLN-326.
RX PubMed=11815426; DOI=10.1161/hc0402.102990;
RA Niimura H., Patton K.K., McKenna W.J., Soults J., Maron B.J., Seidman J.G.,
RA Seidman C.E.;
RT "Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the
RT elderly.";
RL Circulation 105:446-451(2002).
RN [21]
RP VARIANTS LEU-147; GLY-236; GLN-326; MET-896 AND HIS-1138.
RX PubMed=12110947; DOI=10.1007/s00109-002-0323-9;
RA Jaeaeskelaeinen P., Kuusisto J., Miettinen R., Kaerkkaeinen P.,
RA Kaerkkaeinen S., Heikkinen S., Peltola P., Pihlajamaeki J., Vauhkonen I.,
RA Laakso M.;
RT "Mutations in the cardiac myosin-binding protein C gene are the predominant
RT cause of familial hypertrophic cardiomyopathy in eastern Finland.";
RL J. Mol. Med. 80:412-422(2002).
RN [22]
RP VARIANTS CMH4 LYS-258; HIS-810; GLN-820 AND HIS-873.
RX PubMed=12951062; DOI=10.1016/j.bbrc.2003.08.014;
RA Nanni L., Pieroni M., Chimenti C., Simionati B., Zimbello R., Maseri A.,
RA Frustaci A., Lanfranchi G.;
RT "Hypertrophic cardiomyopathy: two homozygous cases with 'typical'
RT hypertrophic cardiomyopathy and three new mutations in cases with
RT progression to dilated cardiomyopathy.";
RL Biochem. Biophys. Res. Commun. 309:391-398(2003).
RN [23]
RP VARIANTS CMH4 PRO-257; LYS-258; GLU-278; ALA-279; PRO-352; TRP-502; LYS-504
RP DEL; GLN-542; ARG-811; VAL-833; THR-1194 AND THR-1255, AND VARIANTS GLN-326
RP AND MET-896.
RX PubMed=12707239; DOI=10.1161/01.cir.0000066323.15244.54;
RA Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., Pichereau C.,
RA Benaiche A., Isnard R., Dubourg O., Burban M., Gueffet J.-P., Millaire A.,
RA Desnos M., Schwartz K., Hainque B., Komajda M.;
RT "Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of
RT mutations, and implications for a molecular diagnosis strategy.";
RL Circulation 107:2227-2232(2003).
RN [24]
RP ERRATUM OF PUBMED:12707239.
RA Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., Pichereau C.,
RA Benaiche A., Isnard R., Dubourg O., Burban M., Gueffet J.-P., Millaire A.,
RA Desnos M., Schwartz K., Hainque B., Komajda M.;
RL Circulation 109:3258-3258(2004).
RN [25]
RP VARIANTS CMH4 LYS-258; TRP-282; ARG-507; TRP-523; ARG-566; PRO-668; VAL-833
RP AND ILE-1115, AND VARIANTS GLY-236 AND GLN-326.
RX PubMed=12974739; DOI=10.1034/j.1399-0004.2003.00151.x;
RA Erdmann J., Daehmlow S., Wischke S., Senyuva M., Werner U., Raible J.,
RA Tanis N., Dyachenko S., Hummel M., Hetzer R., Regitz-Zagrosek V.;
RT "Mutation spectrum in a large cohort of unrelated consecutive patients with
RT hypertrophic cardiomyopathy.";
RL Clin. Genet. 64:339-349(2003).
RN [26]
RP VARIANTS CMH4 SER-161; LYS-258; ASN-605; THR-833; TRP-834 AND THR-1131.
RX PubMed=14563344; DOI=10.1016/s0195-668x(03)00466-4;
RA Alders M., Jongbloed R., Deelen W., van den Wijngaard A., Doevendans P.,
RA Ten Cate F., Regitz-Zagrosek V., Vosberg H.-P., van Langen I., Wilde A.,
RA Dooijes D., Mannens M.;
RT "The 2373insG mutation in the MYBPC3 gene is a founder mutation, which
RT accounts for nearly one-fourth of the HCM cases in the Netherlands.";
RL Eur. Heart J. 24:1848-1853(2003).
RN [27]
RP VARIANT CMH4 GLN-820.
RX PubMed=12628722; DOI=10.1016/s0735-1097(02)02957-1;
RA Konno T., Shimizu M., Ino H., Matsuyama T., Yamaguchi M., Terai H.,
RA Hayashi K., Mabuchi T., Kiyama M., Sakata K., Hayashi T., Inoue M.,
RA Kaneda T., Mabuchi H.;
RT "A novel missense mutation in the myosin binding protein-C gene is
RT responsible for hypertrophic cardiomyopathy with left ventricular
RT dysfunction and dilation in elderly patients.";
RL J. Am. Coll. Cardiol. 41:781-786(2003).
RN [28]
RP VARIANTS CMH4 SER-237; HIS-668 AND THR-833, AND VARIANTS GLN-326 AND
RP MET-896.
RX PubMed=12818575; DOI=10.1016/s0022-2828(03)00146-9;
RA Moerner S., Richard P., Kazzam E., Hellman U., Hainque B., Schwartz K.,
RA Waldenstroem A.;
RT "Identification of the genotypes causing hypertrophic cardiomyopathy in
RT northern Sweden.";
RL J. Mol. Cell. Cardiol. 35:841-849(2003).
RN [29]
RP VARIANTS CMH4 ASN-228; LYS-258; LYS-813 DEL AND THR-833.
RX PubMed=15114369; DOI=10.1038/sj.ejhg.5201190;
RA Andersen P.S., Havndrup O., Bundgaard H., Larsen L.A., Vuust J.,
RA Pedersen A.K., Kjeldsen K., Christiansen M.;
RT "Genetic and phenotypic characterization of mutations in myosin-binding
RT protein C (MYBPC3) in 81 families with familial hypertrophic
RT cardiomyopathy: total or partial haploinsufficiency.";
RL Eur. J. Hum. Genet. 12:673-677(2004).
RN [30]
RP VARIANTS CMH4 ARG-5; LEU-219; ILE-256; LYS-258; HIS-458; ARG-490; GLN-495;
RP TRP-502; GLN-542; VAL-604; ASN-605; LEU-608; CYS-733; ASN-770; ARG-792;
RP HIS-810; LYS-811 DEL; THR-833; GLU-998; ARG-998; ILE-1113 AND THR-1131, AND
RP VARIANTS MET-158; GLY-236; GLN-326; TRP-382; SER-416; ARG-507; MET-545 AND
RP MET-896.
RX PubMed=15519027; DOI=10.1016/j.jacc.2004.07.045;
RA Van Driest S.L., Vasile V.C., Ommen S.R., Will M.L., Tajik A.J.,
RA Gersh B.J., Ackerman M.J.;
RT "Myosin binding protein C mutations and compound heterozygosity in
RT hypertrophic cardiomyopathy.";
RL J. Am. Coll. Cardiol. 44:1903-1910(2004).
RN [31]
RP VARIANT GLY-236.
RX PubMed=15582318; DOI=10.1016/j.jacc.2004.08.058;
RA Hayashi T., Arimura T., Itoh-Satoh M., Ueda K., Hohda S., Inagaki N.,
RA Takahashi M., Hori H., Yasunami M., Nishi H., Koga Y., Nakamura H.,
RA Matsuzaki M., Choi B.Y., Bae S.W., You C.W., Han K.H., Park J.E.,
RA Knoell R., Hoshijima M., Chien K.R., Kimura A.;
RT "Tcap gene mutations in hypertrophic cardiomyopathy and dilated
RT cardiomyopathy.";
RL J. Am. Coll. Cardiol. 44:2192-2201(2004).
RN [32]
RP VARIANTS CMH4 LYS-258; ARG-263; SER-417; HIS-669 AND ASP-759.
RX PubMed=15563892; DOI=10.1016/j.cccn.2004.09.016;
RA Song L., Zou Y., Wang J., Wang Z., Zhen Y., Lou K., Zhang Q., Wang X.,
RA Wang H., Li J., Hui R.;
RT "Mutations profile in Chinese patients with hypertrophic cardiomyopathy.";
RL Clin. Chim. Acta 351:209-216(2005).
RN [33]
RP VARIANT GLY-236, AND VARIANTS CMH4 ASP-342; VAL-627 AND MET-771.
RX PubMed=16004897; DOI=10.1016/j.ijcard.2004.05.060;
RA Garcia-Castro M., Reguero J.R., Alvarez V., Batalla A., Soto M.I.,
RA Albaladejo V., Coto E.;
RT "Hypertrophic cardiomyopathy linked to homozygosity for a new mutation in
RT the myosin-binding protein C gene (A627V) suggests a dosage effect.";
RL Int. J. Cardiol. 102:501-507(2005).
RN [34]
RP VARIANTS CMH4 HIS-273; TRP-502 AND GLN-542, AND VARIANT GLN-326.
RX PubMed=16199542; DOI=10.1136/jmg.2005.033886;
RA Ingles J., Doolan A., Chiu C., Seidman J., Seidman C., Semsarian C.;
RT "Compound and double mutations in patients with hypertrophic
RT cardiomyopathy: implications for genetic testing and counselling.";
RL J. Med. Genet. 42:E59-E59(2005).
RN [35]
RP VARIANTS CMH4 LYS-258; CYS-272; VAL-336; GLN-495; GLN-502; SER-957 AND
RP ILE-958.
RX PubMed=18957093; DOI=10.1186/1471-2350-9-95;
RA Ehlermann P., Weichenhan D., Zehelein J., Steen H., Pribe R., Zeller R.,
RA Lehrke S., Zugck C., Ivandic B.T., Katus H.A.;
RT "Adverse events in families with hypertrophic or dilated cardiomyopathy and
RT mutations in the MYBPC3 gene.";
RL BMC Med. Genet. 9:95-95(2008).
RN [36]
RP VARIANTS CMH4 LYS-334; LYS-814 DEL; GLU-998 AND MET-1046, CHARACTERIZATION
RP OF VARIANTS CMH4 LYS-334; LYS-814 DEL; GLU-998 AND MET-1046, VARIANT
RP GLY-236, AND UBIQUITINATION.
RX PubMed=18929575; DOI=10.1016/j.jmb.2008.09.070;
RA Bahrudin U., Morisaki H., Morisaki T., Ninomiya H., Higaki K., Nanba E.,
RA Igawa O., Takashima S., Mizuta E., Miake J., Yamamoto Y., Shirayoshi Y.,
RA Kitakaze M., Carrier L., Hisatome I.;
RT "Ubiquitin-proteasome system impairment caused by a missense cardiac
RT myosin-binding protein C mutation and associated with cardiac dysfunction
RT in hypertrophic cardiomyopathy.";
RL J. Mol. Biol. 384:896-907(2008).
RN [37]
RP VARIANTS CMH4 GLU-278; ARG-490; GLY-495; GLN-502; TRP-502; ASN-605;
RP SER-1028 AND ARG-1248, AND VARIANTS MET-158; GLY-236; GLN-326; MET-896 AND
RP TRP-1002.
RX PubMed=18403758; DOI=10.1056/nejmoa075463;
RA Morita H., Rehm H.L., Menesses A., McDonough B., Roberts A.E.,
RA Kucherlapati R., Towbin J.A., Seidman J.G., Seidman C.E.;
RT "Shared genetic causes of cardiac hypertrophy in children and adults.";
RL N. Engl. J. Med. 358:1899-1908(2008).
RN [38]
RP VARIANTS CMD1MM ARG-490; THR-833 AND PHE-1264.
RX PubMed=20215591; DOI=10.1161/circgenetics.109.912345;
RA Hershberger R.E., Norton N., Morales A., Li D., Siegfried J.D.,
RA Gonzalez-Quintana J.;
RT "Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and
RT TNNI3 from 312 patients with familial or idiopathic dilated
RT cardiomyopathy.";
RL Circ. Cardiovasc. Genet. 3:155-161(2010).
RN [39]
RP VARIANTS LVNC10 ARG-490 AND LEU-873.
RX PubMed=21551322; DOI=10.1161/circgenetics.110.959270;
RA Probst S., Oechslin E., Schuler P., Greutmann M., Boye P., Knirsch W.,
RA Berger F., Thierfelder L., Jenni R., Klaassen S.;
RT "Sarcomere gene mutations in isolated left ventricular noncompaction
RT cardiomyopathy do not predict clinical phenotype.";
RL Circ. Cardiovasc. Genet. 4:367-374(2011).
RN [40]
RP VARIANT CMH4 VAL-490.
RX PubMed=23840593; DOI=10.1371/journal.pone.0067087;
RA Wang Y., Wang Z., Yang Q., Zou Y., Zhang H., Yan C., Feng X., Chen Y.,
RA Zhang Y., Wang J., Zhou X., Ahmad F., Hui R., Song L.;
RT "Autosomal recessive transmission of MYBPC3 mutation results in malignant
RT phenotype of hypertrophic cardiomyopathy.";
RL PLoS ONE 8:E67087-E67087(2013).
RN [41]
RP INVOLVEMENT IN RCM, AND VARIANT LYS-334.
RX PubMed=26163040; DOI=10.1161/jaha.115.001879;
RA Wu W., Lu C.X., Wang Y.N., Liu F., Chen W., Liu Y.T., Han Y.C., Cao J.,
RA Zhang S.Y., Zhang X.;
RT "Novel phenotype-genotype correlations of restrictive cardiomyopathy with
RT myosin-binding protein C (MYBPC3) gene mutations tested by next-generation
RT sequencing.";
RL J. Am. Heart Assoc. 4:0-0(2015).
RN [42]
RP VARIANT CMH4 VAL-562.
RX PubMed=28265379; DOI=10.1002/ccr3.832;
RA Aurensanz Clemente E., Ayerza Casas A., Garcia Lasheras C.,
RA Ramos Fuentes F., Bueno Martinez I., Pelegrin Diaz J., Ruiz Frontera P.,
RA Montserrat Iglesias L.;
RT "Familial hypertrophic cardiomyopathy associated with a new mutation in
RT gene MYBPC3.";
RL Clin. Case Rep. 5:232-237(2017).
CC -!- FUNCTION: Thick filament-associated protein located in the crossbridge
CC region of vertebrate striated muscle a bands. In vitro it binds MHC, F-
CC actin and native thin filaments, and modifies the activity of actin-
CC activated myosin ATPase. It may modulate muscle contraction or may play
CC a more structural role.
CC -!- INTERACTION:
CC Q14896; Q14896: MYBPC3; NbExp=2; IntAct=EBI-704176, EBI-704176;
CC Q14896; Q5VU43-11: PDE4DIP; NbExp=5; IntAct=EBI-704176, EBI-10769071;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14896-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14896-2; Sequence=VSP_047141;
CC -!- PTM: Substrate for phosphorylation by PKA and PKC. Reversible
CC phosphorylation appears to modulate contraction (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Polyubiquitinated. {ECO:0000269|PubMed:18929575}.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 4 (CMH4) [MIM:115197]: A
CC hereditary heart disorder characterized by ventricular hypertrophy,
CC which is usually asymmetric and often involves the interventricular
CC septum. The symptoms include dyspnea, syncope, collapse, palpitations,
CC and chest pain. They can be readily provoked by exercise. The disorder
CC has inter- and intrafamilial variability ranging from benign to
CC malignant forms with high risk of cardiac failure and sudden cardiac
CC death. {ECO:0000269|PubMed:11499718, ECO:0000269|PubMed:11499719,
CC ECO:0000269|PubMed:11815426, ECO:0000269|PubMed:12379228,
CC ECO:0000269|PubMed:12628722, ECO:0000269|PubMed:12707239,
CC ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:12951062,
CC ECO:0000269|PubMed:12974739, ECO:0000269|PubMed:14563344,
CC ECO:0000269|PubMed:15114369, ECO:0000269|PubMed:15519027,
CC ECO:0000269|PubMed:15563892, ECO:0000269|PubMed:16004897,
CC ECO:0000269|PubMed:16199542, ECO:0000269|PubMed:18403758,
CC ECO:0000269|PubMed:18929575, ECO:0000269|PubMed:18957093,
CC ECO:0000269|PubMed:23840593, ECO:0000269|PubMed:28265379,
CC ECO:0000269|PubMed:7744002, ECO:0000269|PubMed:9048664,
CC ECO:0000269|PubMed:9541104, ECO:0000269|PubMed:9541115,
CC ECO:0000269|PubMed:9562578}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cardiomyopathy, dilated 1MM (CMD1MM) [MIM:615396]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. {ECO:0000269|PubMed:20215591}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=MYBPC3 mutations may be involved in restrictive
CC cardiomyopathy (RCM), a rare non-ischemic myocardial disease. RCM is
CC characterized by restrictive ventricular-filling physiology in the
CC presence of normal or reduced diastolic and/or systolic volumes (of 1
CC or both ventricles), biatrial enlargement, and normal ventricular wall
CC thickness. {ECO:0000269|PubMed:26163040}.
CC -!- DISEASE: Left ventricular non-compaction 10 (LVNC10) [MIM:615396]: A
CC form of left ventricular non-compaction, a cardiomyopathy due to
CC myocardial morphogenesis arrest and characterized by a hypertrophic
CC left ventricle, a severely thickened 2-layered myocardium, numerous
CC prominent trabeculations, deep intertrabecular recesses, and poor
CC systolic function. Clinical manifestations are variable. Some affected
CC individuals experience no symptoms at all, others develop heart
CC failure. In some cases, left ventricular non-compaction is associated
CC with other congenital heart anomalies. LVNC10 is an autosomal dominant
CC condition. {ECO:0000269|PubMed:21551322}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. MyBP family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mybpc3/";
CC ---------------------------------------------------------------------------
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DR EMBL; X84075; CAA58882.1; -; mRNA.
DR EMBL; Y10129; CAA71216.1; -; Genomic_DNA.
DR EMBL; U91629; AAC04620.1; -; Genomic_DNA.
DR EMBL; AY518390; AAR89909.1; -; Genomic_DNA.
DR EMBL; GU324918; ADL14489.1; -; Genomic_DNA.
DR EMBL; AC090582; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC136543; AAI36544.1; -; mRNA.
DR EMBL; BC136546; AAI36547.1; -; mRNA.
DR EMBL; BC142685; AAI42686.1; -; mRNA.
DR EMBL; BC151211; AAI51212.1; -; mRNA.
DR EMBL; S80778; AAB35662.1; -; mRNA.
DR CCDS; CCDS53621.1; -. [Q14896-1]
DR PIR; S55050; S55050.
DR RefSeq; NP_000247.2; NM_000256.3. [Q14896-1]
DR PDB; 1GXE; NMR; -; A=641-770.
DR PDB; 1PD6; NMR; -; A=358-451.
DR PDB; 2AVG; NMR; -; A=151-260.
DR PDB; 2K1M; NMR; -; A=2-96.
DR PDB; 2MQ0; NMR; -; A=453-543.
DR PDB; 2MQ3; NMR; -; A=453-543.
DR PDB; 2V6H; X-ray; 1.55 A; A=151-258.
DR PDB; 3CX2; X-ray; 1.30 A; A=151-258.
DR PDB; 5K6P; NMR; -; A=319-451.
DR PDB; 6CXI; EM; 11.00 A; G/H/I/J/K/L=151-258, M/N/O/P/Q=1-101.
DR PDB; 6CXJ; EM; 11.00 A; G/H/I/J/K/L=151-258, M/N/O/P/Q=1-101.
DR PDB; 6G2T; EM; 9.00 A; G/H/I/J/K/L=151-258.
DR PDB; 7LRG; EM; 6.10 A; G/H/I/J/K/L=358-451.
DR PDBsum; 1GXE; -.
DR PDBsum; 1PD6; -.
DR PDBsum; 2AVG; -.
DR PDBsum; 2K1M; -.
DR PDBsum; 2MQ0; -.
DR PDBsum; 2MQ3; -.
DR PDBsum; 2V6H; -.
DR PDBsum; 3CX2; -.
DR PDBsum; 5K6P; -.
DR PDBsum; 6CXI; -.
DR PDBsum; 6CXJ; -.
DR PDBsum; 6G2T; -.
DR PDBsum; 7LRG; -.
DR AlphaFoldDB; Q14896; -.
DR BMRB; Q14896; -.
DR SASBDB; Q14896; -.
DR SMR; Q14896; -.
DR BioGRID; 110692; 11.
DR IntAct; Q14896; 17.
DR MINT; Q14896; -.
DR STRING; 9606.ENSP00000442795; -.
DR GlyGen; Q14896; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14896; -.
DR PhosphoSitePlus; Q14896; -.
DR BioMuta; MYBPC3; -.
DR DMDM; 425906074; -.
DR UCD-2DPAGE; Q14896; -.
DR MassIVE; Q14896; -.
DR PaxDb; Q14896; -.
DR PeptideAtlas; Q14896; -.
DR PRIDE; Q14896; -.
DR ProteomicsDB; 60216; -. [Q14896-1]
DR ProteomicsDB; 727; -.
DR Antibodypedia; 36699; 225 antibodies from 36 providers.
DR DNASU; 4607; -.
DR Ensembl; ENST00000545968.6; ENSP00000442795.1; ENSG00000134571.12. [Q14896-1]
DR GeneID; 4607; -.
DR KEGG; hsa:4607; -.
DR MANE-Select; ENST00000545968.6; ENSP00000442795.1; NM_000256.3; NP_000247.2.
DR UCSC; uc058bdz.1; human. [Q14896-1]
DR CTD; 4607; -.
DR DisGeNET; 4607; -.
DR GeneCards; MYBPC3; -.
DR GeneReviews; MYBPC3; -.
DR HGNC; HGNC:7551; MYBPC3.
DR HPA; ENSG00000134571; Tissue enriched (heart).
DR MalaCards; MYBPC3; -.
DR MIM; 115197; phenotype.
DR MIM; 600958; gene.
DR MIM; 615396; phenotype.
DR neXtProt; NX_Q14896; -.
DR OpenTargets; ENSG00000134571; -.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 54260; Left ventricular noncompaction.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA31351; -.
DR VEuPathDB; HostDB:ENSG00000134571; -.
DR eggNOG; ENOG502QWRQ; Eukaryota.
DR GeneTree; ENSGT00940000157698; -.
DR InParanoid; Q14896; -.
DR OMA; DKLHFRI; -.
DR TreeFam; TF351819; -.
DR PathwayCommons; Q14896; -.
DR Reactome; R-HSA-390522; Striated Muscle Contraction.
DR SignaLink; Q14896; -.
DR SIGNOR; Q14896; -.
DR BioGRID-ORCS; 4607; 14 hits in 1069 CRISPR screens.
DR ChiTaRS; MYBPC3; human.
DR EvolutionaryTrace; Q14896; -.
DR GeneWiki; Myosin_binding_protein_C,_cardiac; -.
DR GenomeRNAi; 4607; -.
DR Pharos; Q14896; Tbio.
DR PRO; PR:Q14896; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q14896; protein.
DR Bgee; ENSG00000134571; Expressed in apex of heart and 126 other tissues.
DR ExpressionAtlas; Q14896; baseline and differential.
DR Genevisible; Q14896; HS.
DR GO; GO:0031672; C:A band; IDA:BHF-UCL.
DR GO; GO:0014705; C:C zone; NAS:BHF-UCL.
DR GO; GO:0097512; C:cardiac myofibril; IDA:CAFA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030017; C:sarcomere; IDA:BHF-UCL.
DR GO; GO:0005863; C:striated muscle myosin thick filament; IDA:BHF-UCL.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0001671; F:ATPase activator activity; ISS:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017022; F:myosin binding; IDA:BHF-UCL.
DR GO; GO:0032036; F:myosin heavy chain binding; IPI:BHF-UCL.
DR GO; GO:0008307; F:structural constituent of muscle; IMP:BHF-UCL.
DR GO; GO:0031432; F:titin binding; NAS:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; ISS:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0003007; P:heart morphogenesis; IMP:BHF-UCL.
DR GO; GO:0032781; P:positive regulation of ATP-dependent activity; ISS:BHF-UCL.
DR GO; GO:0032971; P:regulation of muscle filament sliding; ISS:BHF-UCL.
DR GO; GO:0006942; P:regulation of striated muscle contraction; ISS:BHF-UCL.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:HGNC-UCL.
DR CDD; cd00063; FN3; 3.
DR Gene3D; 2.60.40.10; -; 11.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR040849; MyBP-C_THB.
DR Pfam; PF00041; fn3; 3.
DR Pfam; PF07679; I-set; 8.
DR Pfam; PF18362; THB; 1.
DR SMART; SM00060; FN3; 3.
DR SMART; SM00409; IG; 8.
DR SMART; SM00408; IGc2; 6.
DR SUPFAM; SSF48726; SSF48726; 8.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 3.
DR PROSITE; PS50835; IG_LIKE; 6.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative splicing;
KW Cardiomyopathy; Cell adhesion; Disease variant; Disulfide bond;
KW Immunoglobulin domain; Metal-binding; Methylation; Muscle protein;
KW Phosphoprotein; Reference proteome; Repeat; Thick filament;
KW Ubl conjugation; Zinc.
FT CHAIN 1..1274
FT /note="Myosin-binding protein C, cardiac-type"
FT /id="PRO_0000072693"
FT DOMAIN 153..256
FT /note="Ig-like C2-type 1"
FT DOMAIN 362..452
FT /note="Ig-like C2-type 2"
FT DOMAIN 453..543
FT /note="Ig-like C2-type 3"
FT DOMAIN 544..633
FT /note="Ig-like C2-type 4"
FT DOMAIN 645..771
FT /note="Ig-like C2-type 5"
FT DOMAIN 774..870
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 872..967
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 971..1065
FT /note="Ig-like C2-type 6"
FT DOMAIN 1068..1163
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1181..1274
FT /note="Ig-like C2-type 7"
FT REGION 107..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 208
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:18926831"
FT BINDING 210
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:18926831"
FT BINDING 223
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:18926831"
FT BINDING 225
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:18926831"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O70468"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70468"
FT MOD_RES 275
FT /note="Phosphoserine; by PKA and PKC"
FT /evidence="ECO:0000250|UniProtKB:O70468"
FT MOD_RES 284
FT /note="Phosphoserine; by PKA and PKC"
FT /evidence="ECO:0000250|UniProtKB:O70468"
FT MOD_RES 304
FT /note="Phosphoserine; by PKA and PKC"
FT /evidence="ECO:0000250|UniProtKB:O70468"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70468"
FT MOD_RES 427
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70468"
FT MOD_RES 550
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70468"
FT MOD_RES 607
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P56741"
FT MOD_RES 1241
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O70468"
FT DISULFID 436..443
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 408..409
FT /note="SK -> R (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_047141"
FT VARIANT 5
FT /note="G -> R (in CMH4; dbSNP:rs201278114)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029390"
FT VARIANT 59
FT /note="T -> A (in CMH4; dbSNP:rs121909375)"
FT /evidence="ECO:0000269|PubMed:11815426"
FT /id="VAR_029391"
FT VARIANT 147
FT /note="P -> L (in dbSNP:rs730880615)"
FT /evidence="ECO:0000269|PubMed:12110947"
FT /id="VAR_074538"
FT VARIANT 158
FT /note="V -> M (in dbSNP:rs3729986)"
FT /evidence="ECO:0000269|PubMed:15519027,
FT ECO:0000269|PubMed:18403758, ECO:0000269|Ref.4"
FT /id="VAR_020085"
FT VARIANT 161
FT /note="P -> S (in CMH4; dbSNP:rs397516053)"
FT /evidence="ECO:0000269|PubMed:14563344"
FT /id="VAR_029392"
FT VARIANT 189
FT /note="V -> I (in dbSNP:rs11570052)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_020568"
FT VARIANT 219
FT /note="V -> L (in CMH4; dbSNP:rs397516068)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029393"
FT VARIANT 228
FT /note="D -> N (in CMH4; dbSNP:rs369300885)"
FT /evidence="ECO:0000269|PubMed:15114369"
FT /id="VAR_029394"
FT VARIANT 236
FT /note="S -> G (in dbSNP:rs3729989)"
FT /evidence="ECO:0000269|PubMed:12110947,
FT ECO:0000269|PubMed:12379228, ECO:0000269|PubMed:12974739,
FT ECO:0000269|PubMed:15519027, ECO:0000269|PubMed:15582318,
FT ECO:0000269|PubMed:16004897, ECO:0000269|PubMed:18403758,
FT ECO:0000269|PubMed:18929575, ECO:0000269|Ref.4"
FT /id="VAR_020086"
FT VARIANT 237
FT /note="Y -> S (in CMH4; dbSNP:rs397516070)"
FT /evidence="ECO:0000269|PubMed:12818575"
FT /id="VAR_029395"
FT VARIANT 256
FT /note="V -> I (in CMH4; dbSNP:rs1444087775)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029396"
FT VARIANT 257
FT /note="H -> P (in CMH4; dbSNP:rs890299857)"
FT /evidence="ECO:0000269|PubMed:12707239"
FT /id="VAR_019889"
FT VARIANT 258
FT /note="E -> K (in CMH4; dbSNP:rs397516074)"
FT /evidence="ECO:0000269|PubMed:12707239,
FT ECO:0000269|PubMed:12951062, ECO:0000269|PubMed:12974739,
FT ECO:0000269|PubMed:14563344, ECO:0000269|PubMed:15114369,
FT ECO:0000269|PubMed:15519027, ECO:0000269|PubMed:15563892,
FT ECO:0000269|PubMed:18957093"
FT /id="VAR_019890"
FT VARIANT 263
FT /note="G -> R (in CMH4; dbSNP:rs373730381)"
FT /evidence="ECO:0000269|PubMed:15563892"
FT /id="VAR_042740"
FT VARIANT 272
FT /note="R -> C (in CMH4; unknown pathological significance;
FT dbSNP:rs397516075)"
FT /evidence="ECO:0000269|PubMed:18957093"
FT /id="VAR_070449"
FT VARIANT 273
FT /note="R -> H (in CMH4; unknown pathological significance;
FT dbSNP:rs376461745)"
FT /evidence="ECO:0000269|PubMed:16199542"
FT /id="VAR_042741"
FT VARIANT 278
FT /note="G -> E (in CMH4; benign variant; dbSNP:rs147315081)"
FT /evidence="ECO:0000269|PubMed:12707239,
FT ECO:0000269|PubMed:18403758"
FT /id="VAR_019891"
FT VARIANT 279
FT /note="G -> A (in CMH4; unknown pathological significance;
FT dbSNP:rs375774648)"
FT /evidence="ECO:0000269|PubMed:12707239"
FT /id="VAR_019892"
FT VARIANT 281
FT /note="R -> Q (in dbSNP:rs11570060)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_020569"
FT VARIANT 282
FT /note="R -> W (in CMH4; dbSNP:rs727504234)"
FT /evidence="ECO:0000269|PubMed:11499719,
FT ECO:0000269|PubMed:12974739"
FT /id="VAR_029397"
FT VARIANT 326
FT /note="R -> Q (in dbSNP:rs34580776)"
FT /evidence="ECO:0000269|PubMed:11499718,
FT ECO:0000269|PubMed:11815426, ECO:0000269|PubMed:12110947,
FT ECO:0000269|PubMed:12379228, ECO:0000269|PubMed:12707239,
FT ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:12974739,
FT ECO:0000269|PubMed:15519027, ECO:0000269|PubMed:16199542,
FT ECO:0000269|PubMed:18403758"
FT /id="VAR_019893"
FT VARIANT 334
FT /note="E -> K (in CMH4; also found in a patient with RCM;
FT decreases protein abundance; increases polyubiquitination
FT level; accelerates the degradation process; no effect on
FT phosphorylation; decreases endopeptidase activity;
FT increases apoptotic process; dbSNP:rs573916965)"
FT /evidence="ECO:0000269|PubMed:18929575,
FT ECO:0000269|PubMed:26163040"
FT /id="VAR_074539"
FT VARIANT 336
FT /note="I -> V (in CMH4)"
FT /evidence="ECO:0000269|PubMed:18957093"
FT /id="VAR_070450"
FT VARIANT 342
FT /note="V -> D (in CMH4; dbSNP:rs730880709)"
FT /evidence="ECO:0000269|PubMed:16004897"
FT /id="VAR_074540"
FT VARIANT 352
FT /note="L -> P (in CMH4; dbSNP:rs1460895809)"
FT /evidence="ECO:0000269|PubMed:12707239"
FT /id="VAR_019894"
FT VARIANT 382
FT /note="R -> W (in dbSNP:rs11570076)"
FT /evidence="ECO:0000269|PubMed:15519027, ECO:0000269|Ref.4"
FT /id="VAR_020570"
FT VARIANT 383
FT /note="L -> V (in dbSNP:rs11570077)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_020571"
FT VARIANT 416
FT /note="G -> S (in dbSNP:rs371513491)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029398"
FT VARIANT 417
FT /note="A -> S (in CMH4)"
FT /evidence="ECO:0000269|PubMed:15563892"
FT /id="VAR_042742"
FT VARIANT 451
FT /note="E -> Q (in CMH4; dbSNP:rs786204338)"
FT /evidence="ECO:0000269|PubMed:9562578"
FT /id="VAR_027879"
FT VARIANT 458
FT /note="R -> H (in CMH4; dbSNP:rs374255707)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029399"
FT VARIANT 490
FT /note="G -> R (in CMH4, CMD1MM and LVNC10;
FT dbSNP:rs200625851)"
FT /evidence="ECO:0000269|PubMed:15519027,
FT ECO:0000269|PubMed:18403758, ECO:0000269|PubMed:20215591,
FT ECO:0000269|PubMed:21551322"
FT /id="VAR_029400"
FT VARIANT 490
FT /note="G -> V (in CMH4; dbSNP:rs397514752)"
FT /evidence="ECO:0000269|PubMed:23840593"
FT /id="VAR_070451"
FT VARIANT 495
FT /note="R -> G (in CMH4; dbSNP:rs397515905)"
FT /evidence="ECO:0000269|PubMed:18403758"
FT /id="VAR_045929"
FT VARIANT 495
FT /note="R -> Q (in CMH4; dbSNP:rs200411226)"
FT /evidence="ECO:0000269|PubMed:11499718,
FT ECO:0000269|PubMed:15519027, ECO:0000269|PubMed:18957093,
FT ECO:0000269|PubMed:9562578"
FT /id="VAR_027880"
FT VARIANT 502
FT /note="R -> Q (in CMH4; dbSNP:rs397515907)"
FT /evidence="ECO:0000269|PubMed:18403758,
FT ECO:0000269|PubMed:18957093, ECO:0000269|PubMed:9562578"
FT /id="VAR_027881"
FT VARIANT 502
FT /note="R -> W (in CMH4; dbSNP:rs375882485)"
FT /evidence="ECO:0000269|PubMed:12707239,
FT ECO:0000269|PubMed:15519027, ECO:0000269|PubMed:16199542,
FT ECO:0000269|PubMed:18403758"
FT /id="VAR_019895"
FT VARIANT 504
FT /note="Missing (in CMH4; dbSNP:rs727504287)"
FT /evidence="ECO:0000269|PubMed:12707239"
FT /id="VAR_019896"
FT VARIANT 507
FT /note="G -> R (in CMH4; dbSNP:rs35736435)"
FT /evidence="ECO:0000269|PubMed:11499719,
FT ECO:0000269|PubMed:12974739, ECO:0000269|PubMed:15519027"
FT /id="VAR_029401"
FT VARIANT 522
FT /note="A -> T (in dbSNP:rs11570082)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_020573"
FT VARIANT 523
FT /note="G -> W (in CMH4; dbSNP:rs1168604846)"
FT /evidence="ECO:0000269|PubMed:12974739"
FT /id="VAR_029402"
FT VARIANT 542
FT /note="E -> Q (in CMH4; dbSNP:rs121909374)"
FT /evidence="ECO:0000269|PubMed:12707239,
FT ECO:0000269|PubMed:15519027, ECO:0000269|PubMed:16199542,
FT ECO:0000269|PubMed:9048664"
FT /id="VAR_003917"
FT VARIANT 545
FT /note="L -> M (in dbSNP:rs377163678)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029403"
FT VARIANT 562
FT /note="A -> V (in CMH4; dbSNP:rs730880694)"
FT /evidence="ECO:0000269|PubMed:28265379"
FT /id="VAR_079521"
FT VARIANT 566
FT /note="C -> R (in CMH4; dbSNP:rs730880695)"
FT /evidence="ECO:0000269|PubMed:11499719,
FT ECO:0000269|PubMed:12974739"
FT /id="VAR_029404"
FT VARIANT 604
FT /note="D -> V (in CMH4; dbSNP:rs1172145591)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029405"
FT VARIANT 605
FT /note="D -> N (in CMH4; unknown pathological significance;
FT dbSNP:rs376736293)"
FT /evidence="ECO:0000269|PubMed:14563344,
FT ECO:0000269|PubMed:15519027, ECO:0000269|PubMed:18403758"
FT /id="VAR_029406"
FT VARIANT 608
FT /note="P -> L (in CMH4; dbSNP:rs778623429)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029407"
FT VARIANT 627
FT /note="A -> V (in CMH4; dbSNP:rs1352376969)"
FT /evidence="ECO:0000269|PubMed:16004897"
FT /id="VAR_074541"
FT VARIANT 654
FT /note="R -> H (in CMH4; unknown pathological significance;
FT as well folded and stable as the wild-type;
FT dbSNP:rs1800565)"
FT /evidence="ECO:0000269|PubMed:12787675,
FT ECO:0000269|PubMed:9541115"
FT /id="VAR_003918"
FT VARIANT 668
FT /note="R -> H (in CMH4; dbSNP:rs727503191)"
FT /evidence="ECO:0000269|PubMed:12818575"
FT /id="VAR_029408"
FT VARIANT 668
FT /note="R -> P (in CMH4; dbSNP:rs727503191)"
FT /evidence="ECO:0000269|PubMed:12974739"
FT /id="VAR_029409"
FT VARIANT 669
FT /note="L -> H (in CMH4)"
FT /evidence="ECO:0000269|PubMed:15563892"
FT /id="VAR_042743"
FT VARIANT 733
FT /note="R -> C (in CMH4; unknown pathological significance;
FT dbSNP:rs397515956)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029410"
FT VARIANT 755
FT /note="N -> K (in CMH4; destabilizes the structure of Ig-
FT like C2-type domain 5; dbSNP:rs1060501474)"
FT /evidence="ECO:0000269|PubMed:12787675,
FT ECO:0000269|PubMed:9541104"
FT /id="VAR_003919"
FT VARIANT 759
FT /note="E -> D (in CMH4; dbSNP:rs765629179)"
FT /evidence="ECO:0000269|PubMed:15563892"
FT /id="VAR_042744"
FT VARIANT 770
FT /note="D -> N (in CMH4; dbSNP:rs36211723)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029411"
FT VARIANT 771
FT /note="V -> M (in CMH4; dbSNP:rs371488302)"
FT /evidence="ECO:0000269|PubMed:16004897"
FT /id="VAR_074542"
FT VARIANT 792
FT /note="W -> R (in CMH4; dbSNP:rs187830361)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029412"
FT VARIANT 810
FT /note="R -> H (in CMH4; dbSNP:rs375675796)"
FT /evidence="ECO:0000269|PubMed:12951062,
FT ECO:0000269|PubMed:15519027"
FT /id="VAR_029413"
FT VARIANT 811
FT /note="K -> R (in CMH4; dbSNP:rs1338707268)"
FT /evidence="ECO:0000269|PubMed:12707239"
FT /id="VAR_019897"
FT VARIANT 811
FT /note="Missing (in CMH4; dbSNP:rs727504288)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029414"
FT VARIANT 813
FT /note="Missing (in CMH4)"
FT /evidence="ECO:0000269|PubMed:15114369"
FT /id="VAR_029415"
FT VARIANT 814
FT /note="Missing (in CMH4; no effect on protein abundance; no
FT effect on endopeptidase activity)"
FT /evidence="ECO:0000269|PubMed:18929575"
FT /id="VAR_074543"
FT VARIANT 820
FT /note="R -> Q (in CMH4; dbSNP:rs2856655)"
FT /evidence="ECO:0000269|PubMed:12628722,
FT ECO:0000269|PubMed:12951062, ECO:0000269|PubMed:7744002,
FT ECO:0000269|PubMed:9048664"
FT /id="VAR_029416"
FT VARIANT 833
FT /note="A -> T (in CMH4 and CMD1MM; dbSNP:rs199865688)"
FT /evidence="ECO:0000269|PubMed:12818575,
FT ECO:0000269|PubMed:14563344, ECO:0000269|PubMed:15114369,
FT ECO:0000269|PubMed:15519027, ECO:0000269|PubMed:20215591"
FT /id="VAR_029417"
FT VARIANT 833
FT /note="A -> V (in CMH4; benign variant; dbSNP:rs3729952)"
FT /evidence="ECO:0000269|PubMed:12707239,
FT ECO:0000269|PubMed:12974739, ECO:0000269|Ref.4"
FT /id="VAR_019898"
FT VARIANT 834
FT /note="R -> T (in CMH4)"
FT /id="VAR_029418"
FT VARIANT 834
FT /note="R -> W (in CMH4; unknown pathological significance;
FT dbSNP:rs752007810)"
FT /evidence="ECO:0000269|PubMed:14563344"
FT /id="VAR_029419"
FT VARIANT 873
FT /note="P -> H (in CMH4; dbSNP:rs371401403)"
FT /evidence="ECO:0000269|PubMed:12951062"
FT /id="VAR_029420"
FT VARIANT 873
FT /note="P -> L (in LVNC10; dbSNP:rs371401403)"
FT /evidence="ECO:0000269|PubMed:21551322"
FT /id="VAR_070452"
FT VARIANT 896
FT /note="V -> M (may act as a phenotype modifier in
FT cardiomyopathy patients; dbSNP:rs35078470)"
FT /evidence="ECO:0000269|PubMed:10521296,
FT ECO:0000269|PubMed:12110947, ECO:0000269|PubMed:12707239,
FT ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:15519027,
FT ECO:0000269|PubMed:18403758"
FT /id="VAR_019899"
FT VARIANT 948
FT /note="N -> T (in CMH4; dbSNP:rs121909376)"
FT /evidence="ECO:0000269|PubMed:12379228"
FT /id="VAR_029421"
FT VARIANT 957
FT /note="T -> S (in CMH4; dbSNP:rs193922380)"
FT /evidence="ECO:0000269|PubMed:18957093"
FT /id="VAR_070453"
FT VARIANT 958
FT /note="T -> I (in CMH4; dbSNP:rs376504548)"
FT /evidence="ECO:0000269|PubMed:18957093"
FT /id="VAR_070454"
FT VARIANT 998
FT /note="Q -> E (in CMH4; no effect on protein abundance; no
FT effect on endopeptidase activity; dbSNP:rs11570112)"
FT /evidence="ECO:0000269|PubMed:15519027,
FT ECO:0000269|PubMed:18929575, ECO:0000269|Ref.4"
FT /id="VAR_020574"
FT VARIANT 998
FT /note="Q -> R (in CMH4; dbSNP:rs727503177)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029422"
FT VARIANT 1002
FT /note="R -> Q (in CMH4; dbSNP:rs727504235)"
FT /evidence="ECO:0000269|PubMed:11815426"
FT /id="VAR_029423"
FT VARIANT 1002
FT /note="R -> W (in dbSNP:rs3729799)"
FT /evidence="ECO:0000269|PubMed:18403758"
FT /id="VAR_029424"
FT VARIANT 1003
FT /note="P -> Q (in CMH4)"
FT /id="VAR_029425"
FT VARIANT 1028
FT /note="T -> S (in CMH4; dbSNP:rs397516002)"
FT /evidence="ECO:0000269|PubMed:18403758"
FT /id="VAR_045930"
FT VARIANT 1046
FT /note="T -> M (in CMH4; no effect on protein abundance; no
FT effect on endopeptidase activity; dbSNP:rs371061770)"
FT /evidence="ECO:0000269|PubMed:18929575"
FT /id="VAR_074544"
FT VARIANT 1048
FT /note="R -> C (in dbSNP:rs11570113)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_020575"
FT VARIANT 1113
FT /note="F -> I (in CMH4; dbSNP:rs1393559112)"
FT /evidence="ECO:0000269|PubMed:15519027"
FT /id="VAR_029426"
FT VARIANT 1115
FT /note="V -> I (in CMH4; dbSNP:rs531189495)"
FT /evidence="ECO:0000269|PubMed:11499719,
FT ECO:0000269|PubMed:12974739"
FT /id="VAR_029427"
FT VARIANT 1131
FT /note="I -> T (in CMH4; unknown pathological significance;
FT dbSNP:rs370890951)"
FT /evidence="ECO:0000269|PubMed:14563344,
FT ECO:0000269|PubMed:15519027"
FT /id="VAR_029428"
FT VARIANT 1138
FT /note="R -> H (in dbSNP:rs187705120)"
FT /evidence="ECO:0000269|PubMed:12110947"
FT /id="VAR_074545"
FT VARIANT 1155
FT /note="Missing (in CMH4)"
FT /id="VAR_029429"
FT VARIANT 1194
FT /note="A -> T (in CMH4; dbSNP:rs397516026)"
FT /evidence="ECO:0000269|PubMed:12707239"
FT /id="VAR_019900"
FT VARIANT 1248
FT /note="G -> R (in CMH4; unknown pathological significance;
FT dbSNP:rs202147520)"
FT /evidence="ECO:0000269|PubMed:18403758"
FT /id="VAR_045931"
FT VARIANT 1255
FT /note="A -> T (in CMH4; dbSNP:rs727503167)"
FT /evidence="ECO:0000269|PubMed:12707239"
FT /id="VAR_019901"
FT VARIANT 1264
FT /note="C -> F (in CMD1MM; dbSNP:rs397514751)"
FT /evidence="ECO:0000269|PubMed:20215591"
FT /id="VAR_070455"
FT CONFLICT 248
FT /note="D -> E (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 302..303
FT /note="RD -> SS (in Ref. 4; AAR89909)"
FT /evidence="ECO:0000305"
FT CONFLICT 536
FT /note="A -> R (in Ref. 1; CAA58882)"
FT /evidence="ECO:0000305"
FT STRAND 19..22
FT /evidence="ECO:0007829|PDB:2K1M"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:2K1M"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:2K1M"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:2K1M"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:2K1M"
FT STRAND 56..60
FT /evidence="ECO:0007829|PDB:2K1M"
FT STRAND 63..70
FT /evidence="ECO:0007829|PDB:2K1M"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:2K1M"
FT STRAND 86..95
FT /evidence="ECO:0007829|PDB:2K1M"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:2AVG"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:3CX2"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:3CX2"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:2AVG"
FT STRAND 188..193
FT /evidence="ECO:0007829|PDB:3CX2"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:3CX2"
FT HELIX 199..202
FT /evidence="ECO:0007829|PDB:3CX2"
FT STRAND 207..214
FT /evidence="ECO:0007829|PDB:3CX2"
FT TURN 215..218
FT /evidence="ECO:0007829|PDB:3CX2"
FT STRAND 219..226
FT /evidence="ECO:0007829|PDB:3CX2"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:3CX2"
FT STRAND 235..242
FT /evidence="ECO:0007829|PDB:3CX2"
FT STRAND 247..257
FT /evidence="ECO:0007829|PDB:3CX2"
FT HELIX 321..326
FT /evidence="ECO:0007829|PDB:5K6P"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:5K6P"
FT HELIX 333..339
FT /evidence="ECO:0007829|PDB:5K6P"
FT HELIX 345..355
FT /evidence="ECO:0007829|PDB:5K6P"
FT STRAND 366..368
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 371..376
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 381..386
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 388..392
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 395..403
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 407..415
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 418..423
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 427..430
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 432..438
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 441..443
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 446..450
FT /evidence="ECO:0007829|PDB:1PD6"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:2MQ0"
FT STRAND 465..467
FT /evidence="ECO:0007829|PDB:2MQ0"
FT STRAND 471..474
FT /evidence="ECO:0007829|PDB:2MQ3"
FT STRAND 475..479
FT /evidence="ECO:0007829|PDB:2MQ0"
FT STRAND 486..488
FT /evidence="ECO:0007829|PDB:2MQ0"
FT STRAND 499..506
FT /evidence="ECO:0007829|PDB:2MQ0"
FT STRAND 509..517
FT /evidence="ECO:0007829|PDB:2MQ0"
FT TURN 519..521
FT /evidence="ECO:0007829|PDB:2MQ3"
FT STRAND 524..528
FT /evidence="ECO:0007829|PDB:2MQ0"
FT STRAND 533..537
FT /evidence="ECO:0007829|PDB:2MQ0"
FT STRAND 650..652
FT /evidence="ECO:0007829|PDB:1GXE"
FT STRAND 658..665
FT /evidence="ECO:0007829|PDB:1GXE"
FT STRAND 670..672
FT /evidence="ECO:0007829|PDB:1GXE"
FT STRAND 675..677
FT /evidence="ECO:0007829|PDB:1GXE"
FT STRAND 680..686
FT /evidence="ECO:0007829|PDB:1GXE"
FT STRAND 722..724
FT /evidence="ECO:0007829|PDB:1GXE"
FT STRAND 726..730
FT /evidence="ECO:0007829|PDB:1GXE"
FT STRAND 733..737
FT /evidence="ECO:0007829|PDB:1GXE"
FT TURN 743..745
FT /evidence="ECO:0007829|PDB:1GXE"
FT STRAND 747..754
FT /evidence="ECO:0007829|PDB:1GXE"
FT STRAND 759..768
FT /evidence="ECO:0007829|PDB:1GXE"
SQ SEQUENCE 1274 AA; 140762 MW; 4E5385C40085B796 CRC64;
MPEPGKKPVS AFSKKPRSVE VAAGSPAVFE AETERAGVKV RWQRGGSDIS ASNKYGLATE
GTRHTLTVRE VGPADQGSYA VIAGSSKVKF DLKVIEAEKA EPMLAPAPAP AEATGAPGEA
PAPAAELGES APSPKGSSSA ALNGPTPGAP DDPIGLFVMR PQDGEVTVGG SITFSARVAG
ASLLKPPVVK WFKGKWVDLS SKVGQHLQLH DSYDRASKVY LFELHITDAQ PAFTGSYRCE
VSTKDKFDCS NFNLTVHEAM GTGDLDLLSA FRRTSLAGGG RRISDSHEDT GILDFSSLLK
KRDSFRTPRD SKLEAPAEED VWEILRQAPP SEYERIAFQY GVTDLRGMLK RLKGMRRDEK
KSTAFQKKLE PAYQVSKGHK IRLTVELADH DAEVKWLKNG QEIQMSGSKY IFESIGAKRT
LTISQCSLAD DAAYQCVVGG EKCSTELFVK EPPVLITRPL EDQLVMVGQR VEFECEVSEE
GAQVKWLKDG VELTREETFK YRFKKDGQRH HLIINEAMLE DAGHYALCTS GGQALAELIV
QEKKLEVYQS IADLMVGAKD QAVFKCEVSD ENVRGVWLKN GKELVPDSRI KVSHIGRVHK
LTIDDVTPAD EADYSFVPEG FACNLSAKLH FMEVKIDFVP RQEPPKIHLD CPGRIPDTIV
VVAGNKLRLD VPISGDPAPT VIWQKAITQG NKAPARPAPD APEDTGDSDE WVFDKKLLCE
TEGRVRVETT KDRSIFTVEG AEKEDEGVYT VTVKNPVGED QVNLTVKVID VPDAPAAPKI
SNVGEDSCTV QWEPPAYDGG QPILGYILER KKKKSYRWMR LNFDLIQELS HEARRMIEGV
VYEMRVYAVN AIGMSRPSPA SQPFMPIGPP SEPTHLAVED VSDTTVSLKW RPPERVGAGG
LDGYSVEYCP EGCSEWVAAL QGLTEHTSIL VKDLPTGARL LFRVRAHNMA GPGAPVTTTE
PVTVQEILQR PRLQLPRHLR QTIQKKVGEP VNLLIPFQGK PRPQVTWTKE GQPLAGEEVS
IRNSPTDTIL FIRAARRVHS GTYQVTVRIE NMEDKATLVL QVVDKPSPPQ DLRVTDAWGL
NVALEWKPPQ DVGNTELWGY TVQKADKKTM EWFTVLEHYR RTHCVVPELI IGNGYYFRVF
SQNMVGFSDR AATTKEPVFI PRPGITYEPP NYKALDFSEA PSFTQPLVNR SVIAGYTAML
CCAVRGSPKP KISWFKNGLD LGEDARFRMF SKQGVLTLEI RKPCPFDGGI YVCRATNLQG
EARCECRLEV RVPQ
