CAC1C_HUMAN
ID CAC1C_HUMAN Reviewed; 2221 AA.
AC Q13936; B2RUT3; E9PDJ0; Q13917; Q13918; Q13919; Q13920; Q13921; Q13922;
AC Q13923; Q13924; Q13925; Q13926; Q13927; Q13928; Q13929; Q13930; Q13932;
AC Q13933; Q14743; Q14744; Q15877; Q4VMI7; Q4VMI8; Q4VMI9; Q6PKM7; Q8N6C0;
AC Q99025; Q99241; Q99875;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 4.
DT 03-AUG-2022, entry version 236.
DE RecName: Full=Voltage-dependent L-type calcium channel subunit alpha-1C;
DE AltName: Full=Calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle;
DE AltName: Full=Voltage-gated calcium channel subunit alpha Cav1.2;
GN Name=CACNA1C; Synonyms=CACH2, CACN2, CACNL1A1, CCHL1A1;
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 [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1), AND
RP VARIANTS VAL-1869 AND ARG-1893.
RC TISSUE=Fetal fibroblast;
RX PubMed=1316612; DOI=10.1073/pnas.89.10.4628;
RA Soldatov N.M.;
RT "Molecular diversity of L-type Ca2+ channel transcripts in human
RT fibroblasts.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:4628-4632(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 18 AND 28), NUCLEOTIDE SEQUENCE
RP [GENOMIC DNA] OF 1822-1863, FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND VARIANT ARG-84.
RC TISSUE=Heart;
RX PubMed=8392192; DOI=10.1073/pnas.90.13.6228;
RA Schultz D., Mikala G., Yatani A., Engle D.B., Iles D.E., Segers B.,
RA Sinke R.J., Weghuis D.O., Kloeckner U., Wakamori M., Wang J.-J., Melvin D.,
RA Varadi G., Schwartz A.;
RT "Cloning, chromosomal localization, and functional expression of the alpha-
RT 1 subunit of the L-type voltage-dependent calcium channel from normal human
RT heart.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6228-6232(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 1112-1803
RP (ISOFORMS 24/27), AND NUCLEOTIDE SEQUENCE [MRNA] OF 1364-1972 (ISOFORMS
RP 11/12/19/20/21/22/23/30/31/32).
RC TISSUE=Hippocampus, and Lung fibroblast;
RX PubMed=7959794; DOI=10.1006/geno.1994.1347;
RA Soldatov N.M.;
RT "Genomic structure of human L-type Ca2+ channel.";
RL Genomics 22:77-87(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 12; 19 AND 20), ALTERNATIVE SPLICING,
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLY-954 AND TYR-958.
RC TISSUE=Fibroblast;
RX PubMed=7737988; DOI=10.1074/jbc.270.18.10540;
RA Soldatov N.M., Bouron A., Reuter H.;
RT "Different voltage-dependent inhibition by dihydropyridines of human Ca2+
RT channel splice variants.";
RL J. Biol. Chem. 270:10540-10543(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 16 AND 17), ALTERNATIVE
RP SPLICING, FUNCTION, SUBCELLULAR LOCATION, AND VARIANTS ARG-84; VAL-1869 AND
RP ARG-1893.
RC TISSUE=Heart;
RX PubMed=9087614; DOI=10.1152/ajpheart.1997.272.3.h1372;
RA Kloeckner U., Mikala G., Eisfeld J., Iles D.E., Strobeck M., Mershon J.L.,
RA Schwartz A., Varadi G.;
RT "Properties of three COOH-terminal splice variants of a human cardiac L-
RT type Ca2+-channel alpha1-subunit.";
RL Am. J. Physiol. 272:H1372-H1381(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 26 AND 27), ALTERNATIVE SPLICING
RP (ISOFORMS 9 AND 10), FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Hippocampus;
RX PubMed=9013606; DOI=10.1074/jbc.272.6.3560;
RA Soldatov N.M., Zuelke R.D., Bouron A., Reuter H.;
RT "Molecular structures involved in L-type calcium channel inactivation. Role
RT of the carboxyl-terminal region encoded by exons 40-42 in alpha1C subunit
RT in the kinetics and Ca2+ dependence of inactivation.";
RL J. Biol. Chem. 272:3560-3566(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 21; 22 AND 23), FUNCTION, ACTIVITY
RP REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=9607315; DOI=10.1016/s0014-5793(98)00425-6;
RA Zuehlke R.D., Bouron A., Soldatov N.M., Reuter H.;
RT "Ca2+ channel sensitivity towards the blocker isradipine is affected by
RT alternative splicing of the human alpha1C subunit gene.";
RL FEBS Lett. 427:220-224(1998).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12), FUNCTION, ACTIVITY REGULATION,
RP SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH CACNB2, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Intestinal smooth muscle;
RX PubMed=12176756; DOI=10.1152/ajpcell.00140.2002;
RA Lyford G.L., Strege P.R., Shepard A., Ou Y., Ermilov L., Miller S.M.,
RA Gibbons S.J., Rae J.L., Szurszewski J.H., Farrugia G.;
RT "Alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive
RT calcium regulation.";
RL Am. J. Physiol. 283:C1001-C1008(2002).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 13; 14; 15; 24 AND 25), FUNCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17071743; DOI=10.1073/pnas.0606539103;
RA Tiwari S., Zhang Y., Heller J., Abernethy D.R., Soldatov N.M.;
RT "Atherosclerosis-related molecular alteration of the human CaV1.2 calcium
RT channel alpha1C subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:17024-17029(2006).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 11; 28; 29; 30; 31; 32 AND 33),
RP ALTERNATIVE SPLICING, AND VARIANTS ARG-84; VAL-1869 AND ARG-1893.
RA Soldatov N.;
RT "Functional expression of splice variants of human l-type calcium channel
RT (isoform 1 gene).";
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 35).
RC TISSUE=Brain;
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 [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-180 (ISOFORM 34), FUNCTION, SUBCELLULAR
RP LOCATION, SUBUNIT, AND INTERACTION WITH CACNB2.
RX PubMed=11741969; DOI=10.1074/jbc.c100642200;
RA Blumenstein Y., Kanevsky N., Sahar G., Barzilai R., Ivanina T., Dascal N.;
RT "A novel long N-terminal isoform of human L-type Ca2+ channel is up-
RT regulated by protein kinase C.";
RL J. Biol. Chem. 277:3419-3423(2002).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1182-1503 (ISOFORMS 6/12/20/23/24), AND
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1182-1503 (ISOFORMS 7/13/16/17/18/21/22).
RC TISSUE=Heart;
RX PubMed=2173707; DOI=10.1016/s0021-9258(17)30522-7;
RA Perez-Reyes E., Wei X., Castellano A., Birnbaumer L.;
RT "Molecular diversity of L-type calcium channels. Evidence for alternative
RT splicing of the transcripts of three non-allelic genes.";
RL J. Biol. Chem. 265:20430-20436(1990).
RN [15]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1140-1206.
RC TISSUE=Heart;
RX PubMed=1653763; DOI=10.1016/0888-7543(91)90471-p;
RA Powers P.A., Gregg R.G., Lalley P.A., Liao M., Hogan K.;
RT "Assignment of the human gene for the alpha 1 subunit of the cardiac DHP-
RT sensitive Ca2+ channel (CCHL1A1) to chromosome 12p12-pter.";
RL Genomics 10:835-839(1991).
RN [16]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1196-1421.
RC TISSUE=Brain;
RX PubMed=1335957; DOI=10.1016/s0888-7543(05)80135-1;
RA Sun W., McPherson J.D., Hoang D.Q., Wasmuth J.J., Evans G.A., Montal M.;
RT "Mapping of a human brain voltage-gated calcium channel to human chromosome
RT 12p13-pter.";
RL Genomics 14:1092-1094(1992).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION, MUTAGENESIS,
RP CALCIUM-BINDING, AND SITE.
RX PubMed=8099908; DOI=10.1016/s0021-9258(19)38613-2;
RA Tang S., Mikala G., Bahinski A., Yatani A., Varadi G., Schwartz A.;
RT "Molecular localization of ion selectivity sites within the pore of a human
RT L-type cardiac calcium channel.";
RL J. Biol. Chem. 268:13026-13029(1993).
RN [18]
RP INTERACTION WITH CACNA2D4, IDENTIFICATION IN A COMPLEX WITH CACNB3 AND
RP CACNA2D4, SUBUNIT, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12181424; DOI=10.1124/mol.62.3.485;
RA Qin N., Yagel S., Momplaisir M.-L., Codd E.E., D'Andrea M.R.;
RT "Molecular cloning and characterization of the human voltage-gated calcium
RT channel alpha(2)delta-4 subunit.";
RL Mol. Pharmacol. 62:485-496(2002).
RN [19]
RP INTERACTION WITH CABP1.
RX PubMed=15140941; DOI=10.1523/jneurosci.5523-03.2004;
RA Zhou H., Kim S.-A., Kirk E.A., Tippens A.L., Sun H., Haeseleer F., Lee A.;
RT "Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with
RT Cav1.2 (L-type) Ca2+ channels.";
RL J. Neurosci. 24:4698-4708(2004).
RN [20]
RP INTERACTION WITH CABP1.
RX PubMed=15980432; DOI=10.1074/jbc.m504167200;
RA Zhou H., Yu K., McCoy K.L., Lee A.;
RT "Molecular mechanism for divergent regulation of Cav1.2 Ca2+ channels by
RT calmodulin and Ca2+-binding protein-1.";
RL J. Biol. Chem. 280:29612-29619(2005).
RN [21]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, SUBUNIT, AND
RP INTERACTION WITH STAC2 AND STAC3.
RX PubMed=29078335; DOI=10.1073/pnas.1708852114;
RA Wong King Yuen S.M., Campiglio M., Tung C.C., Flucher B.E., Van Petegem F.;
RT "Structural insights into binding of STAC proteins to voltage-gated calcium
RT channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E9520-E9528(2017).
RN [22]
RP PHOSPHORYLATION AT SER-1981 BY PKA, AND FUNCTION.
RX PubMed=28119464; DOI=10.1126/scisignal.aaf9647;
RA Nystoriak M.A., Nieves-Cintron M., Patriarchi T., Buonarati O.R.,
RA Prada M.P., Morotti S., Grandi E., Fernandes J.D., Forbush K., Hofmann F.,
RA Sasse K.C., Scott J.D., Ward S.M., Hell J.W., Navedo M.F.;
RT "Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2
RT and vasoconstriction during acute hyperglycemia and diabetes.";
RL Sci. Signal. 10:0-0(2017).
RN [23]
RP FUNCTION, ACTIVITY REGULATION, ALTERNATIVE SPLICING, INTERACTION WITH
RP CALM1; CACNA2D1; CACNB2 AND CACNB3, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=29742403; DOI=10.1016/j.bpj.2018.03.029;
RA Bartels P., Yu D., Huang H., Hu Z., Herzig S., Soong T.W.;
RT "Alternative Splicing at N Terminus and Domain I Modulates CaV1.2
RT Inactivation and Surface Expression.";
RL Biophys. J. 114:2095-2106(2018).
RN [24]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH INFLUENZAVIRUS H1
RP HEMAGGLUTININ (MICROBIAL INFECTION).
RX PubMed=29779930; DOI=10.1016/j.chom.2018.04.015;
RA Fujioka Y., Nishide S., Ose T., Suzuki T., Kato I., Fukuhara H.,
RA Fujioka M., Horiuchi K., Satoh A.O., Nepal P., Kashiwagi S., Wang J.,
RA Horiguchi M., Sato Y., Paudel S., Nanbo A., Miyazaki T., Hasegawa H.,
RA Maenaka K., Ohba Y.;
RT "Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into
RT Mammalian Cells.";
RL Cell Host Microbe 23:809-818(2018).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 428-445 IN COMPLEX WITH CACNB2.
RX PubMed=15141227; DOI=10.1038/nature02588;
RA Van Petegem F., Clark K.A., Chatelain F.C., Minor D.L. Jr.;
RT "Structure of a complex between a voltage-gated calcium channel beta-
RT subunit and an alpha-subunit domain.";
RL Nature 429:671-675(2004).
RN [26] {ECO:0007744|PDB:2BE6}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1659-1692, FUNCTION, SUBCELLULAR
RP LOCATION, INTERACTION WITH CALM1, AND MUTAGENESIS OF 1666-PHE--PHE-1670 AND
RP ILE-1672.
RX PubMed=16299511; DOI=10.1038/nsmb1027;
RA Van Petegem F., Chatelain F.C., Minor D.L. Jr.;
RT "Insights into voltage-gated calcium channel regulation from the structure
RT of the CaV1.2 IQ domain-Ca2+/calmodulin complex.";
RL Nat. Struct. Mol. Biol. 12:1108-1115(2005).
RN [27] {ECO:0007744|PDB:2F3Z}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 1665-1685 IN COMPLEX WITH CALM1.
RX PubMed=16338416; DOI=10.1016/j.str.2005.09.021;
RA Fallon J.L., Halling D.B., Hamilton S.L., Quiocho F.A.;
RT "Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac
RT Ca(v)1.2 calcium channel.";
RL Structure 13:1881-1886(2005).
RN [28] {ECO:0007744|PDB:3G43}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1609-1682 IN COMPLEX WITH CALM1.
RX PubMed=19279214; DOI=10.1073/pnas.0807487106;
RA Fallon J.L., Baker M.R., Xiong L., Loy R.E., Yang G., Dirksen R.T.,
RA Hamilton S.L., Quiocho F.A.;
RT "Crystal structure of dimeric cardiac L-type calcium channel regulatory
RT domains bridged by Ca2+* calmodulins.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:5135-5140(2009).
RN [29] {ECO:0007744|PDB:3OXQ}
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 1609-1685 IN COMPLEX WITH CALM1,
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH CACNB2 AND
RP CACNA2D1, AND MUTAGENESIS OF LEU-1610.
RX PubMed=20953164; DOI=10.1038/emboj.2010.260;
RA Kim E.Y., Rumpf C.H., Van Petegem F., Arant R.J., Findeisen F.,
RA Cooley E.S., Isacoff E.Y., Minor D.L. Jr.;
RT "Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not
RT mediate channel dimerization.";
RL EMBO J. 29:3924-3938(2010).
RN [30] {ECO:0007744|PDB:2LQC}
RP STRUCTURE BY NMR OF 47-68 IN COMPLEX WITH CALMODULIN, AND INTERACTION WITH
RP CALM1.
RX PubMed=22518098; DOI=10.3389/fnmol.2012.00038;
RA Liu Z., Vogel H.J.;
RT "Structural basis for the regulation of L-type voltage-gated calcium
RT channels: interactions between the N-terminal cytoplasmic domain and
RT Ca(2+)-calmodulin.";
RL Front. Mol. Neurosci. 5:38-38(2012).
RN [31]
RP VARIANT TS ARG-406, CHARACTERIZATION OF VARIANT TS ARG-406, FUNCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15454078; DOI=10.1016/j.cell.2004.09.011;
RA Splawski I., Timothy K.W., Sharpe L.M., Decher N., Kumar P., Bloise R.,
RA Napolitano C., Schwartz P.J., Joseph R.M., Condouris K., Tager-Flusberg H.,
RA Priori S.G., Sanguinetti M.C., Keating M.T.;
RT "Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder
RT including arrhythmia and autism.";
RL Cell 119:19-31(2004).
RN [32]
RP VARIANT TS SER-402, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CACNB2
RP AND CACNA2D1, AND SUBUNIT.
RX PubMed=15863612; DOI=10.1073/pnas.0502506102;
RA Splawski I., Timothy K.W., Decher N., Kumar P., Sachse F.B., Beggs A.H.,
RA Sanguinetti M.C., Keating M.T.;
RT "Severe arrhythmia disorder caused by cardiac L-type calcium channel
RT mutations.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8089-8096(2005).
RN [33]
RP VARIANTS BRGDA3 VAL-39 AND ARG-490, CHARACTERIZATION OF VARIANTS BRGDA3
RP VAL-39 AND ARG-490, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH
RP CACNB2, AND SUBUNIT.
RX PubMed=17224476; DOI=10.1161/circulationaha.106.668392;
RA Antzelevitch C., Pollevick G.D., Cordeiro J.M., Casis O., Sanguinetti M.C.,
RA Aizawa Y., Guerchicoff A., Pfeiffer R., Oliva A., Wollnik B., Gelber P.,
RA Bonaros E.P. Jr., Burashnikov E., Wu Y., Sargent J.D., Schickel S.,
RA Oberheiden R., Bhatia A., Hsu L.F., Haissaguerre M., Schimpf R.,
RA Borggrefe M., Wolpert C.;
RT "Loss-of-function mutations in the cardiac calcium channel underlie a new
RT clinical entity characterized by ST-segment elevation, short QT intervals,
RT and sudden cardiac death.";
RL Circulation 115:442-449(2007).
RN [34]
RP VARIANT ARG-878.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
RN [35]
RP VARIANTS LQT8 GLU-834; ARG-857; LEU-857 AND GLN-1989, CHARACTERIZATION OF
RP VARIANT LQT8 ARG-857, FUNCTION, AND INVOLVEMENT IN LQT8.
RX PubMed=23677916; DOI=10.1161/circgenetics.113.000138;
RA Boczek N.J., Best J.M., Tester D.J., Giudicessi J.R., Middha S.,
RA Evans J.M., Kamp T.J., Ackerman M.J.;
RT "Exome sequencing and systems biology converge to identify novel mutations
RT in the L-type calcium channel, CACNA1C, linked to autosomal dominant long
RT QT syndrome.";
RL Circ. Cardiovasc. Genet. 6:279-289(2013).
RN [36]
RP VARIANTS LQT8 SER-381; ILE-456; ASP-582; HIS-858 AND CYS-1831,
RP CHARACTERIZATION OF VARIANTS LQT8 SER-381; ILE-456; ASP-582; HIS-858 AND
RP CYS-1831, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP CACNB2 AND CACNA2D1.
RX PubMed=24728418; DOI=10.1093/europace/euu063;
RA Fukuyama M., Wang Q., Kato K., Ohno S., Ding W.G., Toyoda F., Itoh H.,
RA Kimura H., Makiyama T., Ito M., Matsuura H., Horie M.;
RT "Long QT syndrome type 8: novel CACNA1C mutations causing QT prolongation
RT and variant phenotypes.";
RL Europace 16:1828-1837(2014).
RN [37]
RP VARIANTS TS CYS-518 AND HIS-518, CHARACTERIZATION OF VARIANTS TS CYS-518
RP AND HIS-518, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26253506; DOI=10.1161/circep.115.002745;
RA Boczek N.J., Ye D., Jin F., Tester D.J., Huseby A., Bos J.M., Johnson A.J.,
RA Kanter R., Ackerman M.J.;
RT "Identification and functional characterization of a novel CACNA1C-mediated
RT cardiac disorder characterized by prolonged QT intervals with hypertrophic
RT cardiomyopathy, congenital heart defects, and sudden cardiac death.";
RL Circ. Arrhythm. Electrophysiol. 8:1122-1132(2015).
RN [38]
RP VARIANT TS THR-1186, AND CHARACTERIZATION OF VARIANT TS THR-1186.
RX PubMed=25260352; DOI=10.1016/j.hrthm.2014.09.051;
RA Boczek N.J., Miller E.M., Ye D., Nesterenko V.V., Tester D.J.,
RA Antzelevitch C., Czosek R.J., Ackerman M.J., Ware S.M.;
RT "Novel Timothy syndrome mutation leading to increase in CACNA1C window
RT current.";
RL Heart Rhythm 12:211-219(2015).
RN [39]
RP VARIANTS LQT8 THR-28; LYS-477; GLY-860; THR-1186; VAL-1186; THR-1365;
RP MET-1523; LYS-1544; ASN-1787; ILE-1800; LYS-1948; MET-1953 ASN-2081;
RP ILE-2097 AND GLY-2122, CHARACTERIZATION OF VARIANTS LQT8 THR-28; GLY-860;
RP THR-1186; VAL-1186; MET-1523 AND LYS-1544, AND VARIANTS ARG-37; THR-304;
RP SER-817; ILE-1755; GLY-1765; MET-1835; ARG-1843; CYS-1972; GLN-2056 AND
RP SER-2174.
RX PubMed=25633834; DOI=10.1016/j.yjmcc.2015.01.002;
RA Wemhoener K., Friedrich C., Stallmeyer B., Coffey A.J., Grace A.,
RA Zumhagen S., Seebohm G., Ortiz-Bonnin B., Rinne S., Sachse F.B.,
RA Schulze-Bahr E., Decher N.;
RT "Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause
RT non-syndromic long-QT but not Timothy syndrome.";
RL J. Mol. Cell. Cardiol. 80:186-195(2015).
RN [40]
RP VARIANT HIS-1159.
RX PubMed=26637798; DOI=10.1016/j.neuron.2015.11.009;
RA D'Gama A.M., Pochareddy S., Li M., Jamuar S.S., Reiff R.E., Lam A.T.,
RA Sestan N., Walsh C.A.;
RT "Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates
RT Multiple Genetic Mechanisms.";
RL Neuron 88:910-917(2015).
RN [41]
RP VARIANTS GLU-850 DEL AND SER-2091, CHARACTERIZATION OF VARIANTS GLU-850 DEL
RP AND SER-2091, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27218670; DOI=10.1111/chd.12371;
RA Sutphin B.S., Boczek N.J., Barajas-Martinez H., Hu D., Ye D., Tester D.J.,
RA Antzelevitch C., Ackerman M.J.;
RT "Molecular and functional characterization of rare CACNA1C variants in
RT sudden unexplained death in the young.";
RL Congenit. Heart Dis. 11:683-692(2016).
RN [42]
RP VARIANT LQT8 HIS-858.
RX PubMed=30345660; DOI=10.1002/mgg3.476;
RA Gardner R.J.M., Crozier I.G., Binfield A.L., Love D.R., Lehnert K.,
RA Gibson K., Lintott C.J., Snell R.G., Jacobsen J.C., Jones P.P.,
RA Waddell-Smith K.E., Kennedy M.A., Skinner J.R.;
RT "Penetrance and expressivity of the R858H CACNA1C variant in a five-
RT generation pedigree segregating an arrhythmogenic channelopathy.";
RL Mol. Genet. Genomic Med. 7:E00476-E00476(2019).
CC -!- FUNCTION: Pore-forming, alpha-1C subunit of the voltage-gated calcium
CC channel that gives rise to L-type calcium currents (PubMed:8392192,
CC PubMed:7737988, PubMed:9087614, PubMed:9013606, PubMed:9607315,
CC PubMed:12176756, PubMed:17071743, PubMed:11741969, PubMed:8099908,
CC PubMed:12181424, PubMed:29078335, PubMed:29742403, PubMed:16299511,
CC PubMed:20953164, PubMed:15454078, PubMed:15863612, PubMed:17224476,
CC PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:23677916).
CC Mediates influx of calcium ions into the cytoplasm, and thereby
CC triggers calcium release from the sarcoplasm (By similarity). Plays an
CC important role in excitation-contraction coupling in the heart.
CC Required for normal heart development and normal regulation of heart
CC rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476,
CC PubMed:24728418, PubMed:26253506). Required for normal contraction of
CC smooth muscle cells in blood vessels and in the intestine. Essential
CC for normal blood pressure regulation via its role in the contraction of
CC arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type)
CC calcium channels belong to the 'high-voltage activated' (HVA) group
CC (Probable). {ECO:0000250|UniProtKB:P15381, ECO:0000269|PubMed:11741969,
CC ECO:0000269|PubMed:12176756, ECO:0000269|PubMed:12181424,
CC ECO:0000269|PubMed:15454078, ECO:0000269|PubMed:15863612,
CC ECO:0000269|PubMed:16299511, ECO:0000269|PubMed:17071743,
CC ECO:0000269|PubMed:17224476, ECO:0000269|PubMed:20953164,
CC ECO:0000269|PubMed:23677916, ECO:0000269|PubMed:24728418,
CC ECO:0000269|PubMed:26253506, ECO:0000269|PubMed:27218670,
CC ECO:0000269|PubMed:28119464, ECO:0000269|PubMed:29078335,
CC ECO:0000269|PubMed:29742403, ECO:0000269|PubMed:7737988,
CC ECO:0000269|PubMed:8099908, ECO:0000269|PubMed:8392192,
CC ECO:0000269|PubMed:9013606, ECO:0000269|PubMed:9087614,
CC ECO:0000269|PubMed:9607315, ECO:0000305}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Influenzavirus
CC (PubMed:29779930). May play a critical role in allowing virus entry
CC when sialylated and expressed on lung tissues (PubMed:29779930).
CC {ECO:0000269|PubMed:29779930}.
CC -!- ACTIVITY REGULATION: Inhibited by dihydropyridines (DHP), such as
CC isradipine (PubMed:8392192, PubMed:7737988, PubMed:9607315,
CC PubMed:8099908). Inhibited by nifedipine (By similarity). Channel
CC activity is regulated by Ca(2+) and calmodulin (PubMed:29742403)
CC (Probable). Binding of STAC1, STAC2 or STAC3 to a region that overlaps
CC with the calmodulin binding site inhibits channel inactivation by
CC Ca(2+) and calmodulin (PubMed:29078335). Binding of calmodulin or CABP1
CC at the same regulatory sites results in opposite effects on the channel
CC function (PubMed:15140941, PubMed:15980432). Shear stress and pressure
CC increases calcium channel activity (PubMed:12176756).
CC {ECO:0000250|UniProtKB:P15381, ECO:0000269|PubMed:12176756,
CC ECO:0000269|PubMed:15140941, ECO:0000269|PubMed:15980432,
CC ECO:0000269|PubMed:29078335, ECO:0000269|PubMed:29742403,
CC ECO:0000269|PubMed:7737988, ECO:0000269|PubMed:8099908,
CC ECO:0000269|PubMed:8392192, ECO:0000269|PubMed:9607315,
CC ECO:0000305|PubMed:16299511}.
CC -!- SUBUNIT: Component of a calcium channel complex consisting of a pore-
CC forming alpha subunit (CACNA1C) and ancillary beta, gamma and delta
CC subunits (PubMed:12181424, PubMed:12176756, PubMed:29742403,
CC PubMed:29078335, PubMed:15141227, PubMed:16299511, PubMed:20953164).
CC The channel complex contains alpha, beta, gamma and delta subunits in a
CC 1:1:1:1 ratio, i.e. it contains only one of each type of subunit
CC (Probable). CACNA1C channel activity is modulated by ancillary
CC subunits, such as CACNB1, CACNB2, CACNB3, CACNA2D1 and CACNA2D4
CC (PubMed:11741969, PubMed:12181424, PubMed:29742403, PubMed:17224476).
CC Interacts with the gamma subunits CACNG4, CACNG6, CACNG7 and CACNG8 (By
CC similarity). Interacts with CACNB1 (By similarity). Interacts with
CC CACNB2 (PubMed:12176756, PubMed:11741969, PubMed:29742403,
CC PubMed:15141227, PubMed:20953164, PubMed:15863612, PubMed:17224476,
CC PubMed:24728418). Identified in a complex with CACNA2D4 and CACNB3
CC (PubMed:12181424). Interacts with CACNB3 (PubMed:12181424,
CC PubMed:29742403). Interacts with CACNA2D1 (PubMed:29742403,
CC PubMed:20953164, PubMed:15863612, PubMed:24728418). Interacts with
CC CACNA2D4 (PubMed:12181424). Interacts with CALM1 (PubMed:29742403,
CC PubMed:16299511, PubMed:16338416, PubMed:19279214, PubMed:20953164,
CC PubMed:22518098). Interacts (via the N-terminus and the C-terminal C
CC and IQ motifs) with CABP1; this inhibits Ca(2+)-dependent channel
CC inactivation (PubMed:15140941, PubMed:15980432). The binding via the C
CC motif is calcium independent whereas the binding via IQ requires the
CC presence of calcium and is mutually exclusive with calmodulin binding
CC (PubMed:15140941). The binding to the cytoplasmic N-terminal domain is
CC calcium independent but is essential for the channel modulation.
CC Interacts (via C-terminal CDB motif) with CABP5; in a calcium-dependent
CC manner (By similarity). Interacts with CIB1; the interaction increases
CC upon cardiomyocytes hypertrophy (By similarity). Interacts with STAC2
CC and STAC3; this inhibits channel inactivation (PubMed:29078335).
CC {ECO:0000250|UniProtKB:P15381, ECO:0000250|UniProtKB:Q01815,
CC ECO:0000269|PubMed:11741969, ECO:0000269|PubMed:12176756,
CC ECO:0000269|PubMed:12181424, ECO:0000269|PubMed:15140941,
CC ECO:0000269|PubMed:15141227, ECO:0000269|PubMed:15863612,
CC ECO:0000269|PubMed:15980432, ECO:0000269|PubMed:16299511,
CC ECO:0000269|PubMed:16338416, ECO:0000269|PubMed:17224476,
CC ECO:0000269|PubMed:19279214, ECO:0000269|PubMed:20953164,
CC ECO:0000269|PubMed:22518098, ECO:0000269|PubMed:24728418,
CC ECO:0000269|PubMed:29078335, ECO:0000269|PubMed:29742403, ECO:0000305}.
CC -!- SUBUNIT: (Microbial infection) Interacts with influenzavirus H1
CC hemagglutinin. {ECO:0000269|PubMed:29779930}.
CC -!- INTERACTION:
CC Q13936; P12814: ACTN1; NbExp=2; IntAct=EBI-1038838, EBI-351710;
CC Q13936; Q9NZU7: CABP1; NbExp=4; IntAct=EBI-1038838, EBI-907894;
CC Q13936; Q02641-1: CACNB1; NbExp=2; IntAct=EBI-1038838, EBI-15707950;
CC Q13936; Q08289-1: CACNB2; NbExp=4; IntAct=EBI-1038838, EBI-15707999;
CC Q13936; P54284: CACNB3; NbExp=2; IntAct=EBI-1038838, EBI-1184651;
CC Q13936; P62158: CALM3; NbExp=21; IntAct=EBI-1038838, EBI-397435;
CC Q13936; Q9NRD5: PICK1; NbExp=2; IntAct=EBI-1038838, EBI-79165;
CC Q13936; P62161: Calm3; Xeno; NbExp=2; IntAct=EBI-1038838, EBI-397530;
CC Q13936-20; Q9NZU7-2: CABP1; NbExp=2; IntAct=EBI-15896749, EBI-15896740;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11741969,
CC ECO:0000269|PubMed:12176756, ECO:0000269|PubMed:12181424,
CC ECO:0000269|PubMed:15454078, ECO:0000269|PubMed:15863612,
CC ECO:0000269|PubMed:16299511, ECO:0000269|PubMed:17071743,
CC ECO:0000269|PubMed:17224476, ECO:0000269|PubMed:20953164,
CC ECO:0000269|PubMed:24728418, ECO:0000269|PubMed:26253506,
CC ECO:0000269|PubMed:27218670, ECO:0000269|PubMed:29078335,
CC ECO:0000269|PubMed:29742403, ECO:0000269|PubMed:7737988,
CC ECO:0000269|PubMed:8099908, ECO:0000269|PubMed:8392192,
CC ECO:0000269|PubMed:9013606, ECO:0000269|PubMed:9087614,
CC ECO:0000269|PubMed:9607315}; Multi-pass membrane protein {ECO:0000305}.
CC Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P15381}; Multi-pass
CC membrane protein {ECO:0000305}. Perikaryon
CC {ECO:0000250|UniProtKB:P22002}. Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:P22002}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P22002}. Cell membrane, sarcolemma, T-tubule
CC {ECO:0000250|UniProtKB:Q01815}. Note=Colocalizes with ryanodine
CC receptors in distinct clusters at the junctional membrane, where the
CC sarcolemma and the sarcoplasmic reticulum are in close contact. The
CC interaction between RRAD and CACNB2 promotes the expression of CACNA1C
CC at the cell membrane. {ECO:0000250|UniProtKB:P15381}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=37;
CC Comment=Additional isoforms seem to exist. Exons 8A, 21, 22, 31, 32,
CC 33, 40B, 43A, 41A and 45 are alternatively spliced in a variety of
CC combinations. Experimental confirmation may be lacking for some
CC isoforms.;
CC Name=1; Synonyms=HFCC, Fibroblast;
CC IsoId=Q13936-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13936-2; Sequence=VSP_000894;
CC Name=3;
CC IsoId=Q13936-3; Sequence=VSP_000886;
CC Name=4;
CC IsoId=Q13936-4; Sequence=VSP_000887;
CC Name=5;
CC IsoId=Q13936-5; Sequence=VSP_000888;
CC Name=6;
CC IsoId=Q13936-6; Sequence=VSP_000889;
CC Name=7;
CC IsoId=Q13936-7; Sequence=VSP_000890;
CC Name=8;
CC IsoId=Q13936-8; Sequence=VSP_000891;
CC Name=9;
CC IsoId=Q13936-9; Sequence=VSP_000892;
CC Name=10;
CC IsoId=Q13936-10; Sequence=VSP_000893;
CC Name=11; Synonyms=Alpha-1C.90;
CC IsoId=Q13936-11; Sequence=VSP_000895;
CC Name=12; Synonyms=Alpha-1C.70;
CC IsoId=Q13936-12; Sequence=VSP_000888, VSP_000889, VSP_000895;
CC Name=13; Synonyms=Alpha-1C.127;
CC IsoId=Q13936-13; Sequence=VSP_000888, VSP_000890, VSP_000893,
CC VSP_000895;
CC Name=14; Synonyms=Alpha-1C.126;
CC IsoId=Q13936-14; Sequence=VSP_000888, VSP_000889, VSP_022504,
CC VSP_000893, VSP_000895;
CC Name=15; Synonyms=Alpha-1C.125;
CC IsoId=Q13936-15; Sequence=VSP_000888, VSP_000889, VSP_022503,
CC VSP_000893, VSP_000895;
CC Name=16;
CC IsoId=Q13936-16; Sequence=VSP_000885, VSP_000886, VSP_000888,
CC VSP_000890;
CC Name=17;
CC IsoId=Q13936-17; Sequence=VSP_000885, VSP_000886, VSP_000888,
CC VSP_000890, VSP_000895;
CC Name=18; Synonyms=HHT-1;
CC IsoId=Q13936-18; Sequence=VSP_000885, VSP_000886, VSP_000888,
CC VSP_000890, VSP_000894;
CC Name=19; Synonyms=Alpha-1C.76;
CC IsoId=Q13936-19; Sequence=VSP_000887, VSP_000889, VSP_000891,
CC VSP_000895;
CC Name=20; Synonyms=Alpha-1C.77;
CC IsoId=Q13936-20; Sequence=VSP_000887, VSP_000889, VSP_000895;
CC Name=21; Synonyms=Alpha-1C.69;
CC IsoId=Q13936-21; Sequence=VSP_000887, VSP_000890, VSP_000895;
CC Name=22; Synonyms=Alpha-1C.78;
CC IsoId=Q13936-22; Sequence=VSP_000888, VSP_000890, VSP_000895;
CC Name=23; Synonyms=Alpha-1C.105;
CC IsoId=Q13936-23; Sequence=VSP_000886, VSP_000887, VSP_000889,
CC VSP_000895;
CC Name=24; Synonyms=Alpha-1C.71;
CC IsoId=Q13936-24; Sequence=VSP_000888, VSP_000889, VSP_000893,
CC VSP_000895;
CC Name=25; Synonyms=Alpha-1C.73;
CC IsoId=Q13936-25; Sequence=VSP_000888, VSP_000889, VSP_000891,
CC VSP_000893, VSP_000895;
CC Name=26; Synonyms=Alpha-1C.86;
CC IsoId=Q13936-26; Sequence=VSP_000887, VSP_000889, VSP_000892,
CC VSP_000895;
CC Name=27; Synonyms=Alpha-1C.72;
CC IsoId=Q13936-27; Sequence=VSP_000887, VSP_000889, VSP_000893,
CC VSP_000895;
CC Name=28;
CC IsoId=Q13936-28; Sequence=VSP_000885, VSP_000886, VSP_000888,
CC VSP_000889, VSP_000891, VSP_000894;
CC Name=29; Synonyms=Alpha-1C.74;
CC IsoId=Q13936-29; Sequence=VSP_000887, VSP_000889, VSP_000891,
CC VSP_000893, VSP_000895;
CC Name=30; Synonyms=Alpha-1C.87;
CC IsoId=Q13936-30; Sequence=VSP_000889, VSP_000895;
CC Name=31; Synonyms=Alpha-1C.88;
CC IsoId=Q13936-31; Sequence=VSP_000888, VSP_000895;
CC Name=32; Synonyms=Alpha-1C.89;
CC IsoId=Q13936-32; Sequence=VSP_000887, VSP_000891, VSP_000895;
CC Name=33; Synonyms=Alpha-1C.85;
CC IsoId=Q13936-33; Sequence=VSP_000887, VSP_000889;
CC Name=34; Synonyms=Alpha-1C,long-NT;
CC IsoId=Q13936-34; Sequence=VSP_035146;
CC Name=35;
CC IsoId=Q13936-35; Sequence=VSP_035877, VSP_000888, VSP_000890,
CC VSP_000895;
CC Name=36;
CC IsoId=Q13936-36; Sequence=VSP_000886, VSP_000888, VSP_000890;
CC Name=37;
CC IsoId=Q13936-37; Sequence=VSP_000886, VSP_000888, VSP_000890,
CC VSP_000895;
CC -!- TISSUE SPECIFICITY: Detected throughout the brain, including
CC hippocampus, cerebellum and amygdala, throughout the heart and vascular
CC system, including ductus arteriosus, in urinary bladder, and in retina
CC and sclera in the eye (PubMed:15454078). Expressed in brain, heart,
CC jejunum, ovary, pancreatic beta-cells and vascular smooth muscle.
CC Overall expression is reduced in atherosclerotic vascular smooth
CC muscle. {ECO:0000269|PubMed:12176756, ECO:0000269|PubMed:15454078,
CC ECO:0000269|PubMed:17071743, ECO:0000269|PubMed:8392192}.
CC -!- DOMAIN: Each of the four internal repeats contains five hydrophobic
CC transmembrane segments (S1, S2, S3, S5, S6) and one positively charged
CC transmembrane segment (S4). S4 segments probably represent the voltage-
CC sensor and are characterized by a series of positively charged amino
CC acids at every third position. {ECO:0000305}.
CC -!- DOMAIN: Binding of intracellular calcium through the EF-hand motif
CC inhibits the opening of the channel. {ECO:0000250|UniProtKB:P15381}.
CC -!- PTM: Phosphorylation by PKA at Ser-1981 activates the channel. Elevated
CC levels of blood glucose lead to increased phosphorylation by PKA.
CC {ECO:0000269|PubMed:28119464}.
CC -!- DISEASE: Timothy syndrome (TS) [MIM:601005]: Disorder characterized by
CC multiorgan dysfunction including lethal arrhythmias, webbing of fingers
CC and toes, congenital heart disease, immune deficiency, intermittent
CC hypoglycemia, cognitive abnormalities and autism.
CC {ECO:0000269|PubMed:15454078, ECO:0000269|PubMed:15863612,
CC ECO:0000269|PubMed:25260352, ECO:0000269|PubMed:26253506}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Brugada syndrome 3 (BRGDA3) [MIM:611875]: A heart disease
CC characterized by the association of Brugada syndrome with shortened QT
CC intervals. Brugada syndrome is a tachyarrhythmia characterized by right
CC bundle branch block and ST segment elevation on an electrocardiogram
CC (ECG). It can cause the ventricles to beat so fast that the blood is
CC prevented from circulating efficiently in the body. When this situation
CC occurs, the individual will faint and may die in a few minutes if the
CC heart is not reset. {ECO:0000269|PubMed:17224476}. Note=The gene
CC represented in this entry may be involved in disease pathogenesis.
CC -!- DISEASE: Long QT syndrome 8 (LQT8) [MIM:618447]: A form of long QT
CC syndrome, a heart disorder characterized by a prolonged QT interval on
CC the ECG and polymorphic ventricular arrhythmias. They cause syncope and
CC sudden death in response to exercise or emotional stress, and can
CC present with a sentinel event of sudden cardiac death in infancy. LQT8
CC transmission pattern is consistent with autosomal dominant inheritance
CC with incomplete penetrance. {ECO:0000269|PubMed:23677916,
CC ECO:0000269|PubMed:24728418, ECO:0000269|PubMed:25633834,
CC ECO:0000269|PubMed:30345660}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: Contains exon 8a. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Lacks exon 21. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: Lacks exon 22. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Lacks exon 31. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 7]: Lacks exon 32. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 8]: Lacks exon 33. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 9]: Contains exon 40B and 43A. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 10]: Contains exon 41A. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 11]: Lacks exon 45. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 20]: Predominant isoform in atherosclerotic
CC vascular smooth muscle cells. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 26]: Not inhibited by calcium. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 34]: Enhanced by PKC activator. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC 1.A.1.11) family. CACNA1C subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA02500.2; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M92269; AAA17030.1; -; Genomic_DNA.
DR EMBL; M92270; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M92271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M92272; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M92273; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M92274; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M92275; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L04568; AAA02500.2; ALT_FRAME; Genomic_DNA.
DR EMBL; L04569; AAA02501.1; -; mRNA.
DR EMBL; L29529; AAA51899.1; -; mRNA.
DR EMBL; Z26256; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26258; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26259; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26260; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26261; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26262; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26264; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26265; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26266; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26267; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26268; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26269; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26272; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26273; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26274; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26275; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26276; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26277; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26278; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26279; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26280; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26281; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26283; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26284; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26286; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26287; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26288; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z26294; CAA81218.1; -; mRNA.
DR EMBL; Z26295; CAA81219.1; -; mRNA.
DR EMBL; Z26308; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z34809; CAA84340.1; -; mRNA.
DR EMBL; Z34810; CAA84341.1; -; mRNA.
DR EMBL; Z34811; CAA84342.1; -; mRNA.
DR EMBL; Z34812; CAA84343.1; -; mRNA.
DR EMBL; Z34813; CAA84344.1; -; mRNA.
DR EMBL; Z34814; CAA84345.1; -; mRNA.
DR EMBL; Z34815; CAA84346.1; -; mRNA.
DR EMBL; Z34816; CAA84347.1; -; mRNA.
DR EMBL; Z34817; CAA84348.1; -; mRNA.
DR EMBL; Z34818; CAA84349.1; -; mRNA.
DR EMBL; Z34819; CAA84350.1; -; mRNA.
DR EMBL; Z34820; CAA84351.1; -; mRNA.
DR EMBL; Z34821; CAA84352.1; -; mRNA.
DR EMBL; Z34822; CAA84353.1; -; mRNA.
DR EMBL; L29530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L29531; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L29532; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L29533; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L29534; AAA51900.1; -; mRNA.
DR EMBL; L29535; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L29536; AAA51901.1; -; mRNA.
DR EMBL; L29537; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L29538; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L29539; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z74996; CAA99284.1; -; mRNA.
DR EMBL; AJ224873; CAA12174.1; -; mRNA.
DR EMBL; AF465484; AAM70049.1; -; mRNA.
DR EMBL; AY830711; AAX37354.1; -; mRNA.
DR EMBL; AY830712; AAX37355.1; -; mRNA.
DR EMBL; AY830713; AAX37356.1; -; mRNA.
DR EMBL; AC005293; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005342; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005344; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005414; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005866; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006051; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007618; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC146846; AAI46847.1; -; mRNA.
DR EMBL; AY604867; AAT02226.1; -; mRNA.
DR EMBL; M57971; AAA62832.1; -; mRNA.
DR EMBL; M57972; AAB59461.1; -; mRNA.
DR EMBL; M61130; AAA58409.1; -; Genomic_DNA.
DR EMBL; M91370; AAA74590.1; -; Genomic_DNA.
DR CCDS; CCDS44787.1; -. [Q13936-23]
DR CCDS; CCDS44788.1; -. [Q13936-11]
DR CCDS; CCDS44789.1; -. [Q13936-30]
DR CCDS; CCDS44790.1; -. [Q13936-31]
DR CCDS; CCDS44791.1; -. [Q13936-22]
DR CCDS; CCDS44792.1; -. [Q13936-14]
DR CCDS; CCDS44793.1; -. [Q13936-24]
DR CCDS; CCDS44794.1; -. [Q13936-12]
DR CCDS; CCDS44795.1; -. [Q13936-25]
DR CCDS; CCDS44796.1; -. [Q13936-15]
DR CCDS; CCDS44797.1; -. [Q13936-32]
DR CCDS; CCDS44798.1; -. [Q13936-21]
DR CCDS; CCDS44799.1; -. [Q13936-27]
DR CCDS; CCDS44800.1; -. [Q13936-20]
DR CCDS; CCDS44801.1; -. [Q13936-29]
DR CCDS; CCDS53733.1; -. [Q13936-36]
DR CCDS; CCDS53734.1; -. [Q13936-37]
DR CCDS; CCDS53735.1; -. [Q13936-13]
DR CCDS; CCDS53736.1; -. [Q13936-33]
DR PIR; A23660; A23660.
DR PIR; A44363; A44363.
DR PIR; A45290; A45290.
DR PIR; B23660; B23660.
DR PIR; C23660; C23660.
DR PIR; I54168; I54168.
DR RefSeq; NP_000710.5; NM_000719.6. [Q13936-12]
DR RefSeq; NP_001123299.1; NM_001129827.1. [Q13936-11]
DR RefSeq; NP_001123301.1; NM_001129829.1. [Q13936-14]
DR RefSeq; NP_001123302.2; NM_001129830.2.
DR RefSeq; NP_001123303.1; NM_001129831.1. [Q13936-31]
DR RefSeq; NP_001123304.1; NM_001129832.1. [Q13936-30]
DR RefSeq; NP_001123305.1; NM_001129833.1. [Q13936-13]
DR RefSeq; NP_001123306.1; NM_001129834.1. [Q13936-24]
DR RefSeq; NP_001123307.1; NM_001129835.1. [Q13936-27]
DR RefSeq; NP_001123308.1; NM_001129836.1. [Q13936-32]
DR RefSeq; NP_001123309.1; NM_001129837.1. [Q13936-25]
DR RefSeq; NP_001123310.1; NM_001129838.1. [Q13936-29]
DR RefSeq; NP_001123311.1; NM_001129839.1. [Q13936-15]
DR RefSeq; NP_001123312.1; NM_001129840.1. [Q13936-23]
DR RefSeq; NP_001123313.1; NM_001129841.1. [Q13936-21]
DR RefSeq; NP_001123314.1; NM_001129842.1. [Q13936-22]
DR RefSeq; NP_001123315.1; NM_001129843.1. [Q13936-20]
DR RefSeq; NP_001123316.1; NM_001129844.1. [Q13936-35]
DR RefSeq; NP_001123318.1; NM_001129846.1. [Q13936-19]
DR RefSeq; NP_001161095.1; NM_001167623.1. [Q13936-37]
DR RefSeq; NP_001161096.2; NM_001167624.2.
DR RefSeq; NP_001161097.1; NM_001167625.1.
DR RefSeq; NP_955630.3; NM_199460.3.
DR PDB; 1T0J; X-ray; 2.00 A; C=428-445.
DR PDB; 2BE6; X-ray; 2.00 A; D/E/F=1659-1692.
DR PDB; 2F3Y; X-ray; 1.45 A; B=1665-1685.
DR PDB; 2F3Z; X-ray; 1.60 A; B=1665-1685.
DR PDB; 2LQC; NMR; -; B=47-68.
DR PDB; 3G43; X-ray; 2.10 A; E/F=1609-1682.
DR PDB; 3OXQ; X-ray; 2.55 A; E/F=1609-1685.
DR PDB; 5V2P; X-ray; 2.00 A; B=427-445.
DR PDB; 5V2Q; X-ray; 1.70 A; B=427-445.
DR PDB; 6C0A; NMR; -; B=1664-1686.
DR PDB; 6DAD; X-ray; 1.65 A; C/D=1659-1692.
DR PDB; 6DAE; X-ray; 2.00 A; C/D=1659-1692.
DR PDB; 6DAF; X-ray; 2.40 A; C/D=1659-1692.
DR PDB; 6U39; X-ray; 2.40 A; B/D/F/H/J/L/N/P/R/T=1659-1692.
DR PDB; 6U3A; X-ray; 1.65 A; C/D=1659-1692.
DR PDB; 6U3B; X-ray; 1.70 A; B=1659-1692.
DR PDB; 6U3D; X-ray; 1.75 A; C/D=1659-1692.
DR PDBsum; 1T0J; -.
DR PDBsum; 2BE6; -.
DR PDBsum; 2F3Y; -.
DR PDBsum; 2F3Z; -.
DR PDBsum; 2LQC; -.
DR PDBsum; 3G43; -.
DR PDBsum; 3OXQ; -.
DR PDBsum; 5V2P; -.
DR PDBsum; 5V2Q; -.
DR PDBsum; 6C0A; -.
DR PDBsum; 6DAD; -.
DR PDBsum; 6DAE; -.
DR PDBsum; 6DAF; -.
DR PDBsum; 6U39; -.
DR PDBsum; 6U3A; -.
DR PDBsum; 6U3B; -.
DR PDBsum; 6U3D; -.
DR AlphaFoldDB; Q13936; -.
DR BMRB; Q13936; -.
DR SMR; Q13936; -.
DR BioGRID; 107229; 35.
DR ComplexPortal; CPX-3195; Cardiac muscle voltage-gated calcium channel complex.
DR DIP; DIP-29589N; -.
DR IntAct; Q13936; 26.
DR MINT; Q13936; -.
DR STRING; 9606.ENSP00000266376; -.
DR BindingDB; Q13936; -.
DR ChEMBL; CHEMBL1940; -.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB00381; Amlodipine.
DR DrugBank; DB09229; Aranidipine.
DR DrugBank; DB09227; Barnidipine.
DR DrugBank; DB09231; Benidipine.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB01373; Calcium.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR DrugBank; DB09232; Cilnidipine.
DR DrugBank; DB00568; Cinnarizine.
DR DrugBank; DB04920; Clevidipine.
DR DrugBank; DB00343; Diltiazem.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB06751; Drotaverine.
DR DrugBank; DB09235; Efonidipine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00153; Ergocalciferol.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB01023; Felodipine.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB00308; Ibutilide.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB00270; Isradipine.
DR DrugBank; DB09236; Lacidipine.
DR DrugBank; DB09237; Levamlodipine.
DR DrugBank; DB00825; Levomenthol.
DR DrugBank; DB00653; Magnesium sulfate.
DR DrugBank; DB09238; Manidipine.
DR DrugBank; DB01388; Mibefradil.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00622; Nicardipine.
DR DrugBank; DB01115; Nifedipine.
DR DrugBank; DB06712; Nilvadipine.
DR DrugBank; DB00393; Nimodipine.
DR DrugBank; DB00401; Nisoldipine.
DR DrugBank; DB01054; Nitrendipine.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB12278; Propiverine.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB00421; Spironolactone.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB09089; Trimebutine.
DR DrugBank; DB00661; Verapamil.
DR DrugCentral; Q13936; -.
DR GuidetoPHARMACOLOGY; 529; -.
DR TCDB; 1.A.1.11.4; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q13936; 4 sites.
DR iPTMnet; Q13936; -.
DR PhosphoSitePlus; Q13936; -.
DR BioMuta; CACNA1C; -.
DR DMDM; 308153651; -.
DR EPD; Q13936; -.
DR jPOST; Q13936; -.
DR MassIVE; Q13936; -.
DR PaxDb; Q13936; -.
DR PeptideAtlas; Q13936; -.
DR PRIDE; Q13936; -.
DR ProteomicsDB; 19675; -.
DR ProteomicsDB; 59725; -. [Q13936-1]
DR ProteomicsDB; 59726; -. [Q13936-10]
DR ProteomicsDB; 59727; -. [Q13936-11]
DR ProteomicsDB; 59728; -. [Q13936-12]
DR ProteomicsDB; 59729; -. [Q13936-13]
DR ProteomicsDB; 59730; -. [Q13936-14]
DR ProteomicsDB; 59731; -. [Q13936-15]
DR ProteomicsDB; 59732; -. [Q13936-16]
DR ProteomicsDB; 59733; -. [Q13936-17]
DR ProteomicsDB; 59734; -. [Q13936-18]
DR ProteomicsDB; 59735; -. [Q13936-19]
DR ProteomicsDB; 59736; -. [Q13936-2]
DR ProteomicsDB; 59737; -. [Q13936-20]
DR ProteomicsDB; 59738; -. [Q13936-21]
DR ProteomicsDB; 59739; -. [Q13936-22]
DR ProteomicsDB; 59740; -. [Q13936-23]
DR ProteomicsDB; 59741; -. [Q13936-24]
DR ProteomicsDB; 59742; -. [Q13936-25]
DR ProteomicsDB; 59743; -. [Q13936-26]
DR ProteomicsDB; 59744; -. [Q13936-27]
DR ProteomicsDB; 59745; -. [Q13936-28]
DR ProteomicsDB; 59746; -. [Q13936-29]
DR ProteomicsDB; 59747; -. [Q13936-3]
DR ProteomicsDB; 59748; -. [Q13936-30]
DR ProteomicsDB; 59749; -. [Q13936-31]
DR ProteomicsDB; 59750; -. [Q13936-32]
DR ProteomicsDB; 59751; -. [Q13936-33]
DR ProteomicsDB; 59752; -. [Q13936-34]
DR ProteomicsDB; 59753; -. [Q13936-35]
DR ProteomicsDB; 59754; -. [Q13936-4]
DR ProteomicsDB; 59755; -. [Q13936-5]
DR ProteomicsDB; 59756; -. [Q13936-6]
DR ProteomicsDB; 59757; -. [Q13936-7]
DR ProteomicsDB; 59758; -. [Q13936-8]
DR ProteomicsDB; 59759; -. [Q13936-9]
DR ABCD; Q13936; 2 sequenced antibodies.
DR Antibodypedia; 22118; 521 antibodies from 40 providers.
DR DNASU; 775; -.
DR Ensembl; ENST00000344100.7; ENSP00000341092.3; ENSG00000151067.23. [Q13936-14]
DR Ensembl; ENST00000347598.9; ENSP00000266376.6; ENSG00000151067.23. [Q13936-11]
DR Ensembl; ENST00000399591.5; ENSP00000382500.1; ENSG00000151067.23. [Q13936-29]
DR Ensembl; ENST00000399595.5; ENSP00000382504.1; ENSG00000151067.23. [Q13936-25]
DR Ensembl; ENST00000399597.5; ENSP00000382506.1; ENSG00000151067.23. [Q13936-22]
DR Ensembl; ENST00000399601.5; ENSP00000382510.1; ENSG00000151067.23. [Q13936-20]
DR Ensembl; ENST00000399603.6; ENSP00000382512.1; ENSG00000151067.23. [Q13936-37]
DR Ensembl; ENST00000399606.5; ENSP00000382515.1; ENSG00000151067.23. [Q13936-30]
DR Ensembl; ENST00000399621.5; ENSP00000382530.1; ENSG00000151067.23. [Q13936-24]
DR Ensembl; ENST00000399629.5; ENSP00000382537.1; ENSG00000151067.23. [Q13936-32]
DR Ensembl; ENST00000399637.5; ENSP00000382546.1; ENSG00000151067.23. [Q13936-27]
DR Ensembl; ENST00000399638.5; ENSP00000382547.1; ENSG00000151067.23. [Q13936-31]
DR Ensembl; ENST00000399641.6; ENSP00000382549.1; ENSG00000151067.23. [Q13936-23]
DR Ensembl; ENST00000399644.5; ENSP00000382552.1; ENSG00000151067.23. [Q13936-21]
DR Ensembl; ENST00000399649.5; ENSP00000382557.1; ENSG00000151067.23. [Q13936-15]
DR Ensembl; ENST00000399655.6; ENSP00000382563.1; ENSG00000151067.23. [Q13936-12]
DR Ensembl; ENST00000402845.7; ENSP00000385724.3; ENSG00000151067.23. [Q13936-13]
DR Ensembl; ENST00000642583.1; ENSP00000494999.1; ENSG00000285479.2. [Q13936-29]
DR Ensembl; ENST00000643038.2; ENSP00000494095.1; ENSG00000285479.2. [Q13936-11]
DR Ensembl; ENST00000643138.1; ENSP00000496049.1; ENSG00000285479.2. [Q13936-22]
DR Ensembl; ENST00000643701.1; ENSP00000496458.1; ENSG00000285479.2. [Q13936-15]
DR Ensembl; ENST00000643858.1; ENSP00000495576.1; ENSG00000285479.2. [Q13936-14]
DR Ensembl; ENST00000644048.1; ENSP00000494782.1; ENSG00000285479.2. [Q13936-31]
DR Ensembl; ENST00000644235.2; ENSP00000494058.1; ENSG00000285479.2. [Q13936-12]
DR Ensembl; ENST00000644369.2; ENSP00000494765.1; ENSG00000285479.2. [Q13936-23]
DR Ensembl; ENST00000644660.1; ENSP00000496749.1; ENSG00000285479.2. [Q13936-20]
DR Ensembl; ENST00000644691.1; ENSP00000494420.1; ENSG00000285479.2. [Q13936-30]
DR Ensembl; ENST00000644891.1; ENSP00000496681.1; ENSG00000285479.2. [Q13936-32]
DR Ensembl; ENST00000645584.1; ENSP00000494018.1; ENSG00000285479.2. [Q13936-24]
DR Ensembl; ENST00000645965.1; ENSP00000493890.1; ENSG00000285479.2. [Q13936-27]
DR Ensembl; ENST00000646257.1; ENSP00000493573.1; ENSG00000285479.2. [Q13936-21]
DR Ensembl; ENST00000647062.1; ENSP00000495080.1; ENSG00000285479.2. [Q13936-13]
DR Ensembl; ENST00000647327.2; ENSP00000493781.1; ENSG00000285479.2. [Q13936-37]
DR Ensembl; ENST00000647521.1; ENSP00000495678.1; ENSG00000285479.2. [Q13936-25]
DR Ensembl; ENST00000682686.1; ENSP00000507309.1; ENSG00000151067.23. [Q13936-19]
DR Ensembl; ENST00000683482.1; ENSP00000507169.1; ENSG00000151067.23. [Q13936-35]
DR GeneID; 775; -.
DR KEGG; hsa:775; -.
DR MANE-Select; ENST00000399655.6; ENSP00000382563.1; NM_000719.7; NP_000710.5. [Q13936-12]
DR UCSC; uc001qjz.3; human. [Q13936-1]
DR CTD; 775; -.
DR DisGeNET; 775; -.
DR GeneCards; CACNA1C; -.
DR GeneReviews; CACNA1C; -.
DR HGNC; HGNC:1390; CACNA1C.
DR HPA; ENSG00000151067; Tissue enhanced (endometrium, heart muscle, intestine).
DR MalaCards; CACNA1C; -.
DR MIM; 114205; gene.
DR MIM; 601005; phenotype.
DR MIM; 611875; phenotype.
DR MIM; 618447; phenotype.
DR neXtProt; NX_Q13936; -.
DR OpenTargets; ENSG00000151067; -.
DR Orphanet; 130; Brugada syndrome.
DR Orphanet; 101016; Romano-Ward syndrome.
DR Orphanet; 595098; Timothy syndrome type 1.
DR PharmGKB; PA83; -.
DR VEuPathDB; HostDB:ENSG00000151067; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000156127; -.
DR InParanoid; Q13936; -.
DR OMA; FCTDSSK; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q13936; -.
DR TreeFam; TF312805; -.
DR PathwayCommons; Q13936; -.
DR Reactome; R-HSA-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-HSA-419037; NCAM1 interactions.
DR Reactome; R-HSA-422356; Regulation of insulin secretion.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-HSA-5576893; Phase 2 - plateau phase.
DR SignaLink; Q13936; -.
DR SIGNOR; Q13936; -.
DR BioGRID-ORCS; 775; 13 hits in 1073 CRISPR screens.
DR ChiTaRS; CACNA1C; human.
DR EvolutionaryTrace; Q13936; -.
DR GeneWiki; Cav1.2; -.
DR GenomeRNAi; 775; -.
DR Pharos; Q13936; Tclin.
DR PRO; PR:Q13936; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q13936; protein.
DR Bgee; ENSG00000151067; Expressed in apex of heart and 100 other tissues.
DR ExpressionAtlas; Q13936; baseline and differential.
DR Genevisible; Q13936; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:BHF-UCL.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IDA:UniProtKB.
DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL.
DR GO; GO:0051393; F:alpha-actinin binding; IPI:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; IPI:UniProtKB.
DR GO; GO:0008331; F:high voltage-gated calcium channel activity; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:UniProtKB.
DR GO; GO:0086056; F:voltage-gated calcium channel activity involved in AV node cell action potential; IMP:BHF-UCL.
DR GO; GO:0086007; F:voltage-gated calcium channel activity involved in cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0061577; P:calcium ion transmembrane transport via high voltage-gated calcium channel; IDA:BHF-UCL.
DR GO; GO:0060402; P:calcium ion transport into cytosol; ISS:UniProtKB.
DR GO; GO:0035585; P:calcium-mediated signaling using extracellular calcium source; TAS:BHF-UCL.
DR GO; GO:0043010; P:camera-type eye development; IMP:BHF-UCL.
DR GO; GO:0061337; P:cardiac conduction; IMP:UniProtKB.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL.
DR GO; GO:0086064; P:cell communication by electrical coupling involved in cardiac conduction; TAS:BHF-UCL.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IMP:BHF-UCL.
DR GO; GO:0007507; P:heart development; IMP:BHF-UCL.
DR GO; GO:0002520; P:immune system development; IMP:BHF-UCL.
DR GO; GO:0098912; P:membrane depolarization during atrial cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0086045; P:membrane depolarization during AV node cell action potential; IMP:BHF-UCL.
DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0045762; P:positive regulation of adenylate cyclase activity; ISS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; ISS:UniProtKB.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR GO; GO:0098911; P:regulation of ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
DR Gene3D; 1.20.120.350; -; 6.
DR InterPro; IPR031688; CAC1F_C.
DR InterPro; IPR031649; GPHH_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR014873; VDCC_a1su_IQ.
DR InterPro; IPR005451; VDCC_L_a1csu.
DR InterPro; IPR005446; VDCC_L_a1su.
DR InterPro; IPR002077; VDCCAlpha1.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR Pfam; PF08763; Ca_chan_IQ; 1.
DR Pfam; PF16885; CAC1F_C; 2.
DR Pfam; PF16905; GPHH; 1.
DR Pfam; PF00520; Ion_trans; 5.
DR PRINTS; PR00167; CACHANNEL.
DR PRINTS; PR01630; LVDCCALPHA1.
DR PRINTS; PR01635; LVDCCALPHA1C.
DR SMART; SM01062; Ca_chan_IQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autism; Autism spectrum disorder;
KW Brugada syndrome; Calcium; Calcium channel; Calcium transport;
KW Calmodulin-binding; Cell membrane; Cell projection; Disease variant;
KW Disulfide bond; Glycoprotein; Host-virus interaction; Ion channel;
KW Ion transport; Long QT syndrome; Membrane; Metal-binding; Phosphoprotein;
KW Postsynaptic cell membrane; Reference proteome; Repeat; Synapse;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..2221
FT /note="Voltage-dependent L-type calcium channel subunit
FT alpha-1C"
FT /id="PRO_0000053928"
FT TOPO_DOM 1..124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 125..143
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 144..158
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 159..179
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 180..188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 189..209
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 210..232
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 233..251
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 252..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 269..290
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 291..350
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 351..372
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 373..380
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 381..401
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 402..524
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 525..543
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 544..554
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 555..575
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 576..586
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 587..606
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 607..615
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 616..634
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 635..653
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 654..673
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 674..693
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 694..715
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 716..725
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 726..745
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 746..900
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 901..919
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 920..931
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 932..952
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 953..987
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 988..1006
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1007..1013
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1014..1032
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1033..1051
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1052..1071
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1072..1121
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1122..1142
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1143..1159
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1160..1181
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1182..1239
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1240..1261
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1262..1269
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1270..1291
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1292..1301
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1302..1321
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1322..1372
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1373..1391
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1392..1409
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1410..1430
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1431..1452
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1453..1471
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1472..1499
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1500..1524
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1525..2221
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 111..408
FT /note="I"
FT REPEAT 510..756
FT /note="II"
FT REPEAT 887..1189
FT /note="III"
FT REPEAT 1226..1527
FT /note="IV"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 47..68
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:22518098"
FT REGION 73..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..445
FT /note="AID/alpha-interaction domain; mediates interaction
FT with the beta subunit"
FT /evidence="ECO:0000269|PubMed:15141227"
FT REGION 449..481
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 764..861
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 829..876
FT /note="Interaction with STAC2"
FT /evidence="ECO:0000269|PubMed:29078335"
FT REGION 1109..1198
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1478..1546
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1492..1534
FT /note="Phenylalkylamine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1659..1686
FT /note="Important for interaction with STAC1, STAC2 and
FT STAC3"
FT /evidence="ECO:0000250|UniProtKB:P15381"
FT REGION 1665..1685
FT /note="Calmodulin-binding IQ region"
FT /evidence="ECO:0000269|PubMed:16299511,
FT ECO:0000269|PubMed:16338416, ECO:0000269|PubMed:19279214,
FT ECO:0000269|PubMed:20953164"
FT REGION 1699..1718
FT /note="Important for localization in at the junctional
FT membrane"
FT /evidence="ECO:0000250|UniProtKB:P15381"
FT REGION 1778..1847
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2029..2063
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2186..2221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 361..364
FT /note="Selectivity filter of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 704..707
FT /note="Selectivity filter of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 1133..1136
FT /note="Selectivity filter of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 1462..1465
FT /note="Selectivity filter of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT COMPBIAS 764..809
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1778..1823
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2032..2049
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2188..2212
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 363
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 706
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 1135
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT SITE 363
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000269|PubMed:8099908"
FT SITE 1135
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000269|PubMed:8099908"
FT SITE 1464
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000269|PubMed:8099908"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 476
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 815
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 1718
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 1739
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 1981
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:28119464"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1436
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1487
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 298..326
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 316..332
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 1078..1089
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 1479..1495
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT VAR_SEQ 1..29
FT /note="Missing (in isoform 16, isoform 17, isoform 18 and
FT isoform 28)"
FT /evidence="ECO:0000303|PubMed:8392192,
FT ECO:0000303|PubMed:9087614, ECO:0000303|Ref.10"
FT /id="VSP_000885"
FT VAR_SEQ 1..16
FT /note="MVNENTRMYIPEENHQ -> MLRAFVQPGTPAYQPLPSHLSANTEVKFKGTL
FT VHEAQLNYFYISPG (in isoform 34)"
FT /evidence="ECO:0000303|PubMed:11741969"
FT /id="VSP_035146"
FT VAR_SEQ 306..308
FT /note="Missing (in isoform 35)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035877"
FT VAR_SEQ 372..391
FT /note="VNDAVGRDWPWIYFVTLIII -> MQDAMGYELPWVYFVSLVIF (in
FT isoform 3, isoform 16, isoform 17, isoform 18, isoform 23,
FT isoform 28, isoform 36 and isoform 37)"
FT /evidence="ECO:0000303|PubMed:8392192,
FT ECO:0000303|PubMed:9087614, ECO:0000303|PubMed:9607315,
FT ECO:0000303|Ref.10"
FT /id="VSP_000886"
FT VAR_SEQ 932..951
FT /note="Missing (in isoform 4, isoform 19, isoform 20,
FT isoform 21, isoform 23, isoform 26, isoform 27, isoform 29,
FT isoform 32 and isoform 33)"
FT /evidence="ECO:0000303|PubMed:7737988,
FT ECO:0000303|PubMed:9013606, ECO:0000303|PubMed:9607315,
FT ECO:0000303|Ref.10"
FT /id="VSP_000887"
FT VAR_SEQ 952..971
FT /note="Missing (in isoform 5, isoform 12, isoform 13,
FT isoform 14, isoform 15, isoform 16, isoform 17, isoform 18,
FT isoform 22, isoform 24, isoform 25, isoform 28, isoform 31,
FT isoform 35, isoform 36 and isoform 37)"
FT /evidence="ECO:0000303|PubMed:12176756,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17071743,
FT ECO:0000303|PubMed:7737988, ECO:0000303|PubMed:8392192,
FT ECO:0000303|PubMed:9087614, ECO:0000303|PubMed:9607315,
FT ECO:0000303|Ref.10"
FT /id="VSP_000888"
FT VAR_SEQ 1297..1324
FT /note="Missing (in isoform 6, isoform 12, isoform 14,
FT isoform 15, isoform 19, isoform 20, isoform 23, isoform 24,
FT isoform 25, isoform 26, isoform 27, isoform 28, isoform 29,
FT isoform 30 and isoform 33)"
FT /evidence="ECO:0000303|PubMed:12176756,
FT ECO:0000303|PubMed:17071743, ECO:0000303|PubMed:7737988,
FT ECO:0000303|PubMed:8392192, ECO:0000303|PubMed:9013606,
FT ECO:0000303|PubMed:9607315, ECO:0000303|Ref.10"
FT /id="VSP_000889"
FT VAR_SEQ 1325..1352
FT /note="Missing (in isoform 7, isoform 13, isoform 16,
FT isoform 17, isoform 18, isoform 21, isoform 22, isoform 35,
FT isoform 36 and isoform 37)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17071743, ECO:0000303|PubMed:8392192,
FT ECO:0000303|PubMed:9087614, ECO:0000303|PubMed:9607315"
FT /id="VSP_000890"
FT VAR_SEQ 1351..1363
FT /note="Missing (in isoform 15)"
FT /evidence="ECO:0000303|PubMed:17071743"
FT /id="VSP_022503"
FT VAR_SEQ 1353..1363
FT /note="Missing (in isoform 8, isoform 19, isoform 25,
FT isoform 28, isoform 29 and isoform 32)"
FT /evidence="ECO:0000303|PubMed:17071743,
FT ECO:0000303|PubMed:7737988, ECO:0000303|PubMed:8392192,
FT ECO:0000303|Ref.10"
FT /id="VSP_000891"
FT VAR_SEQ 1363
FT /note="M -> MGPSCSHPPLAVLTAPPVADGFQ (in isoform 14)"
FT /evidence="ECO:0000303|PubMed:17071743"
FT /id="VSP_022504"
FT VAR_SEQ 1618..1699
FT /note="LRIKTEGNLEQANEELRAIIKKIWKRTSMKLLDQVVPPAGDDEVTVGKFYAT
FT FLIQEYFRKFKKRKEQGLVGKPSQRNALSL -> LREAELSSQVQYQAKEASLLERRRK
FT SSHPKSSTKPNKLLSSGGSTGWVEDARALEGQVLARGCGWLGSLEERERGPHHPPLGF
FT (in isoform 9 and isoform 26)"
FT /evidence="ECO:0000303|PubMed:9013606"
FT /id="VSP_000892"
FT VAR_SEQ 1623
FT /note="E -> EEGPSPSEAHQGAEDPFRPA (in isoform 10, isoform
FT 13, isoform 14, isoform 15, isoform 24, isoform 25, isoform
FT 27 and isoform 29)"
FT /evidence="ECO:0000303|PubMed:17071743,
FT ECO:0000303|PubMed:9013606, ECO:0000303|Ref.10"
FT /id="VSP_000893"
FT VAR_SEQ 1864..1898
FT /note="Missing (in isoform 11, isoform 12, isoform 13,
FT isoform 14, isoform 15, isoform 17, isoform 19, isoform 20,
FT isoform 21, isoform 22, isoform 23, isoform 24, isoform 25,
FT isoform 26, isoform 27, isoform 29, isoform 30, isoform 31,
FT isoform 32, isoform 35 and isoform 37)"
FT /evidence="ECO:0000303|PubMed:12176756,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17071743,
FT ECO:0000303|PubMed:7737988, ECO:0000303|PubMed:9013606,
FT ECO:0000303|PubMed:9087614, ECO:0000303|PubMed:9607315,
FT ECO:0000303|Ref.10"
FT /id="VSP_000895"
FT VAR_SEQ 1864..1897
FT /note="ERHVPMCEDLELRRDSGSAGTQAHCLLLRKANPS -> MHCCDMLDGGTFPP
FT ALGPRRAPPCLHQQLQGSLAGLREDTPCIVPGHASLCCSSRVGEWLPAGCTAPQHA
FT (in isoform 2, isoform 18 and isoform 28)"
FT /evidence="ECO:0000303|PubMed:8392192, ECO:0000303|Ref.10"
FT /id="VSP_000894"
FT VARIANT 28
FT /note="A -> T (in LQT8; unknown pathological significance;
FT increased channel activity)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075148"
FT VARIANT 37
FT /note="G -> R"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075149"
FT VARIANT 39
FT /note="A -> V (in BRGDA3; unknown pathological
FT significance; affects channel activity)"
FT /evidence="ECO:0000269|PubMed:17224476"
FT /id="VAR_044039"
FT VARIANT 84
FT /note="Q -> R (in dbSNP:rs1051345)"
FT /evidence="ECO:0000269|PubMed:8392192,
FT ECO:0000269|PubMed:9087614, ECO:0000269|Ref.10"
FT /id="VAR_045987"
FT VARIANT 304
FT /note="I -> T"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075150"
FT VARIANT 381
FT /note="P -> S (in LQT8; unknown pathological significance;
FT no effect on channel activity)"
FT /evidence="ECO:0000269|PubMed:24728418"
FT /id="VAR_075151"
FT VARIANT 391
FT /note="I -> L (in dbSNP:rs1051356)"
FT /id="VAR_045988"
FT VARIANT 402
FT /note="G -> S (in TS)"
FT /evidence="ECO:0000269|PubMed:15863612"
FT /id="VAR_026741"
FT VARIANT 406
FT /note="G -> R (in TS; causes a nearly complete loss of
FT voltage-dependent channel inactivation)"
FT /evidence="ECO:0000269|PubMed:15454078"
FT /id="VAR_026742"
FT VARIANT 456
FT /note="M -> I (in LQT8; unknown pathological significance;
FT no effect on channel activity)"
FT /evidence="ECO:0000269|PubMed:24728418"
FT /id="VAR_075152"
FT VARIANT 477
FT /note="E -> K (in LQT8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075153"
FT VARIANT 490
FT /note="G -> R (in BRGDA3; unknown pathological
FT significance; affects channel activity)"
FT /evidence="ECO:0000269|PubMed:17224476"
FT /id="VAR_044040"
FT VARIANT 518
FT /note="R -> C (in TS; only with cardiac manifestation;
FT decreased current density; associated with slower
FT inactivation; altered localization)"
FT /evidence="ECO:0000269|PubMed:26253506"
FT /id="VAR_075154"
FT VARIANT 518
FT /note="R -> H (in TS; only with cardiac manifestation;
FT decreased current density; associated with slower
FT inactivation)"
FT /evidence="ECO:0000269|PubMed:26253506"
FT /id="VAR_075155"
FT VARIANT 582
FT /note="A -> D (in LQT8; gain-of-function effect on channel
FT activity; slower inactivation)"
FT /evidence="ECO:0000269|PubMed:24728418"
FT /id="VAR_075156"
FT VARIANT 752
FT /note="A -> T"
FT /id="VAR_001495"
FT VARIANT 817
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075157"
FT VARIANT 834
FT /note="K -> E (in LQT8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23677916"
FT /id="VAR_082632"
FT VARIANT 850
FT /note="Missing (rare variant; found in a case of sudden
FT unexplained death in the young; unknown pathological
FT significance; results in reduced whole-cell calcium
FT currents)"
FT /evidence="ECO:0000269|PubMed:27218670"
FT /id="VAR_076414"
FT VARIANT 857
FT /note="P -> L (in LQT8)"
FT /evidence="ECO:0000269|PubMed:23677916"
FT /id="VAR_082633"
FT VARIANT 857
FT /note="P -> R (in LQT8; leads to increased calcium
FT currents; increased surface membrane expression of the
FT channel)"
FT /evidence="ECO:0000269|PubMed:23677916"
FT /id="VAR_082634"
FT VARIANT 858
FT /note="R -> H (in LQT8; gain-of-function effect on channel
FT activity; slower inactivation)"
FT /evidence="ECO:0000269|PubMed:24728418,
FT ECO:0000269|PubMed:30345660"
FT /id="VAR_075158"
FT VARIANT 860
FT /note="R -> G (in LQT8; gain-of-function effect on channel
FT activity)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075159"
FT VARIANT 878
FT /note="S -> R (found in a clear cell renal carcinoma case;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064700"
FT VARIANT 1159
FT /note="R -> H (found in a patient with autism; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:26637798"
FT /id="VAR_078701"
FT VARIANT 1186
FT /note="I -> T (in TS and LQT8; electrophysiological
FT phenotype characterized by loss of current density and
FT gain-of-function shift in activation leading to increased
FT steady-state current; gain of function activity)"
FT /evidence="ECO:0000269|PubMed:25260352,
FT ECO:0000269|PubMed:25633834"
FT /id="VAR_072381"
FT VARIANT 1186
FT /note="I -> V (in LQT8; gain of function activity)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075160"
FT VARIANT 1365
FT /note="A -> T (in LQT8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075161"
FT VARIANT 1523
FT /note="I -> M (in LQT8; gain of function activity)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075162"
FT VARIANT 1544
FT /note="E -> K (in LQT8; gain of function activity)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075163"
FT VARIANT 1755
FT /note="V -> I"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075164"
FT VARIANT 1765
FT /note="A -> G"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075165"
FT VARIANT 1787
FT /note="D -> N (in LQT8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075166"
FT VARIANT 1800
FT /note="T -> I (in LQT8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075167"
FT VARIANT 1831
FT /note="G -> C (in LQT8; unknown pathological significance;
FT no effect on channel activity)"
FT /evidence="ECO:0000269|PubMed:24728418"
FT /id="VAR_075168"
FT VARIANT 1835
FT /note="T -> M"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075169"
FT VARIANT 1843
FT /note="G -> R"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075170"
FT VARIANT 1868
FT /note="P -> L (in dbSNP:rs10848683)"
FT /id="VAR_059223"
FT VARIANT 1869
FT /note="M -> V (in dbSNP:rs10774053)"
FT /evidence="ECO:0000269|PubMed:1316612,
FT ECO:0000269|PubMed:9087614, ECO:0000269|Ref.10"
FT /id="VAR_059224"
FT VARIANT 1893
FT /note="K -> R (in dbSNP:rs10774054)"
FT /evidence="ECO:0000269|PubMed:1316612,
FT ECO:0000269|PubMed:9087614, ECO:0000269|Ref.10"
FT /id="VAR_061102"
FT VARIANT 1948
FT /note="E -> K (in LQT8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075171"
FT VARIANT 1953
FT /note="T -> M (in LQT8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075172"
FT VARIANT 1972
FT /note="R -> C"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075173"
FT VARIANT 1989
FT /note="R -> Q (in LQT8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23677916"
FT /id="VAR_082635"
FT VARIANT 2056
FT /note="R -> Q (in dbSNP:rs112414325)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075174"
FT VARIANT 2081
FT /note="T -> N (in LQT8; unknown pathological significance;
FT dbSNP:rs771424529)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075175"
FT VARIANT 2091
FT /note="A -> S (rare variant; found in a case of sudden
FT unexplained death in the young; unknown pathological
FT significance; results in increased whole-cell calcium
FT currents)"
FT /evidence="ECO:0000269|PubMed:27218670"
FT /id="VAR_076415"
FT VARIANT 2097
FT /note="V -> I (in LQT8; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075176"
FT VARIANT 2122
FT /note="A -> G (in LQT8; unknown pathological significance;
FT dbSNP:rs549476254)"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075177"
FT VARIANT 2169
FT /note="A -> T"
FT /id="VAR_001496"
FT VARIANT 2174
FT /note="N -> S"
FT /evidence="ECO:0000269|PubMed:25633834"
FT /id="VAR_075178"
FT MUTAGEN 363
FT /note="E->K: Loss of selectivity for divalent over
FT monovalent cations."
FT /evidence="ECO:0000269|PubMed:8099908"
FT MUTAGEN 954
FT /note="G->F: Affects voltage-dependent inhibition by
FT dihydropyridines; when associated with I-958."
FT /evidence="ECO:0000269|PubMed:7737988"
FT MUTAGEN 958
FT /note="Y->I: Affects voltage-dependent inhibition by
FT dihydropyridines; when associated with F-954."
FT /evidence="ECO:0000269|PubMed:7737988"
FT MUTAGEN 1135
FT /note="E->K: Loss of selectivity for divalent over
FT monovalent cations."
FT /evidence="ECO:0000269|PubMed:8099908"
FT MUTAGEN 1464
FT /note="E->K: Loss of selectivity for divalent over
FT monovalent cations."
FT /evidence="ECO:0000269|PubMed:8099908"
FT MUTAGEN 1610
FT /note="L->A: Loss of a low-affinity interaction with CALM1.
FT No effect on channel inactivation by Ca(2+) and
FT calmodulin."
FT /evidence="ECO:0000269|PubMed:20953164"
FT MUTAGEN 1666..1670
FT /note="FYATF->AAATA: Mildly decreased channel activity. No
FT effect on channel inactivation. Loss of channel
FT inactivation by Ca(2+) and calmodulin; when associated with
FT A-1672."
FT /evidence="ECO:0000269|PubMed:16299511"
FT MUTAGEN 1672
FT /note="I->A: Loss of channel inactivation by Ca(2+) and
FT calmodulin; when associated with 1666-A--A-1670."
FT /evidence="ECO:0000269|PubMed:16299511"
FT CONFLICT 1072
FT /note="K -> Q (in Ref. 3; Z26272)"
FT /evidence="ECO:0000305"
FT CONFLICT 1157
FT /note="N -> K (in Ref. 15; AAA58409)"
FT /evidence="ECO:0000305"
FT CONFLICT 1244
FT /note="L -> P (in Ref. 16; AAA74590)"
FT /evidence="ECO:0000305"
FT CONFLICT 1384
FT /note="L -> P (in Ref. 16; AAA74590)"
FT /evidence="ECO:0000305"
FT CONFLICT 1412
FT /note="A -> V (in Ref. 12; AAI46847)"
FT /evidence="ECO:0000305"
FT CONFLICT 1459
FT /note="R -> K (in Ref. 3; CAA81219)"
FT /evidence="ECO:0000305"
FT CONFLICT 2205
FT /note="R -> A (in Ref. 3; CAA84340/CAA84341/CAA84342/
FT CAA84343/CAA84344/CAA84345/CAA84346/CAA84347/CAA84348/
FT CAA84349/CAA84350/CAA84351, 7; CAA12174 and 9; AAX37354/
FT AAX37355/AAX37356)"
FT /evidence="ECO:0000305"
FT CONFLICT 2205
FT /note="R -> G (in Ref. 1; AAA17030)"
FT /evidence="ECO:0000305"
FT HELIX 48..65
FT /evidence="ECO:0007829|PDB:2LQC"
FT HELIX 429..443
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 1609..1651
FT /evidence="ECO:0007829|PDB:3G43"
FT HELIX 1659..1661
FT /evidence="ECO:0007829|PDB:6U3B"
FT HELIX 1666..1680
FT /evidence="ECO:0007829|PDB:2F3Y"
FT CONFLICT Q13936-26:1573
FT /note="A -> T (in Ref. 3; CAA84348)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2221 AA; 248977 MW; 7E755F7AF4C86769 CRC64;
MVNENTRMYI PEENHQGSNY GSPRPAHANM NANAAAGLAP EHIPTPGAAL SWQAAIDAAR
QAKLMGSAGN ATISTVSSTQ RKRQQYGKPK KQGSTTATRP PRALLCLTLK NPIRRACISI
VEWKPFEIII LLTIFANCVA LAIYIPFPED DSNATNSNLE RVEYLFLIIF TVEAFLKVIA
YGLLFHPNAY LRNGWNLLDF IIVVVGLFSA ILEQATKADG ANALGGKGAG FDVKALRAFR
VLRPLRLVSG VPSLQVVLNS IIKAMVPLLH IALLVLFVII IYAIIGLELF MGKMHKTCYN
QEGIADVPAE DDPSPCALET GHGRQCQNGT VCKPGWDGPK HGITNFDNFA FAMLTVFQCI
TMEGWTDVLY WVNDAVGRDW PWIYFVTLII IGSFFVLNLV LGVLSGEFSK EREKAKARGD
FQKLREKQQL EEDLKGYLDW ITQAEDIDPE NEDEGMDEEK PRNMSMPTSE TESVNTENVA
GGDIEGENCG ARLAHRISKS KFSRYWRRWN RFCRRKCRAA VKSNVFYWLV IFLVFLNTLT
IASEHYNQPN WLTEVQDTAN KALLALFTAE MLLKMYSLGL QAYFVSLFNR FDCFVVCGGI
LETILVETKI MSPLGISVLR CVRLLRIFKI TRYWNSLSNL VASLLNSVRS IASLLLLLFL
FIIIFSLLGM QLFGGKFNFD EMQTRRSTFD NFPQSLLTVF QILTGEDWNS VMYDGIMAYG
GPSFPGMLVC IYFIILFICG NYILLNVFLA IAVDNLADAE SLTSAQKEEE EEKERKKLAR
TASPEKKQEL VEKPAVGESK EEKIELKSIT ADGESPPATK INMDDLQPNE NEDKSPYPNP
ETTGEEDEEE PEMPVGPRPR PLSELHLKEK AVPMPEASAF FIFSSNNRFR LQCHRIVNDT
IFTNLILFFI LLSSISLAAE DPVQHTSFRN HILFYFDIVF TTIFTIEIAL KILGNADYVF
TSIFTLEIIL KMTAYGAFLH KGSFCRNYFN ILDLLVVSVS LISFGIQSSA INVVKILRVL
RVLRPLRAIN RAKGLKHVVQ CVFVAIRTIG NIVIVTTLLQ FMFACIGVQL FKGKLYTCSD
SSKQTEAECK GNYITYKDGE VDHPIIQPRS WENSKFDFDN VLAAMMALFT VSTFEGWPEL
LYRSIDSHTE DKGPIYNYRV EISIFFIIYI IIIAFFMMNI FVGFVIVTFQ EQGEQEYKNC
ELDKNQRQCV EYALKARPLR RYIPKNQHQY KVWYVVNSTY FEYLMFVLIL LNTICLAMQH
YGQSCLFKIA MNILNMLFTG LFTVEMILKL IAFKPKGYFS DPWNVFDFLI VIGSIIDVIL
SETNHYFCDA WNTFDALIVV GSIVDIAITE VNPAEHTQCS PSMNAEENSR ISITFFRLFR
VMRLVKLLSR GEGIRTLLWT FIKSFQALPY VALLIVMLFF IYAVIGMQVF GKIALNDTTE
INRNNNFQTF PQAVLLLFRC ATGEAWQDIM LACMPGKKCA PESEPSNSTE GETPCGSSFA
VFYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH HLDEFKRIWA EYDPEAKGRI
KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVSMNMPLNS DGTVMFNATL FALVRTALRI
KTEGNLEQAN EELRAIIKKI WKRTSMKLLD QVVPPAGDDE VTVGKFYATF LIQEYFRKFK
KRKEQGLVGK PSQRNALSLQ AGLRTLHDIG PEIRRAISGD LTAEEELDKA MKEAVSAASE
DDIFRRAGGL FGNHVSYYQS DGRSAFPQTF TTQRPLHINK AGSSQGDTES PSHEKLVDST
FTPSSYSSTG SNANINNANN TALGRLPRPA GYPSTVSTVE GHGPPLSPAI RVQEVAWKLS
SNRERHVPMC EDLELRRDSG SAGTQAHCLL LRKANPSRCH SRESQAAMAG QEETSQDETY
EVKMNHDTEA CSEPSLLSTE MLSYQDDENR QLTLPEEDKR DIRQSPKRGF LRSASLGRRA
SFHLECLKRQ KDRGGDISQK TVLPLHLVHH QALAVAGLSP LLQRSHSPAS FPRPFATPPA
TPGSRGWPPQ PVPTLRLEGV ESSEKLNSSF PSIHCGSWAE TTPGGGGSSA ARRVRPVSLM
VPSQAGAPGR QFHGSASSLV EAVLISEGLG QFAQDPKFIE VTTQELADAC DMTIEEMESA
ADNILSGGAP QSPNGALLPF VNCRDAGQDR AGGEEDAGCV RARGRPSEEE LQDSRVYVSS
L
