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 27-MAR-2024, entry version 245. 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 INVOLVEMENT IN NEDHLSS, AND VARIANT NEDHLSS MET-1411. RX PubMed=30513141; DOI=10.1002/ajmg.a.40657; RA Bozarth X., Dines J.N., Cong Q., Mirzaa G.M., Foss K., RA Lawrence Merritt J. II, Thies J., Mefford H.C., Novotny E.; RT "Expanding clinical phenotype in CACNA1C related disorders: From neonatal RT onset severe epileptic encephalopathy to late-onset epilepsy."; RL Am. J. Med. Genet. A 176:2733-2739(2018). RN [43] RP VARIANT TS PHE-643, CHARACTERIZATION OF VARIANT TS PHE-643, AND FUNCTION. RX PubMed=30023270; DOI=10.1016/j.hrcr.2018.03.003; RA Ozawa J., Ohno S., Saito H., Saitoh A., Matsuura H., Horie M.; RT "A novel CACNA1C mutation identified in a patient with Timothy syndrome RT without syndactyly exerts both marked loss- and gain-of-function effects."; RL HeartRhythm Case Rep. 4:273-277(2018). RN [44] RP VARIANT TS LYS-1135, CHARACTERIZATION OF VARIANT TS LYS-1135, AND FUNCTION. RX PubMed=30172029; DOI=10.1016/j.hrthm.2018.08.030; RA Ye D., Tester D.J., Zhou W., Papagiannis J., Ackerman M.J.; RT "A pore-localizing CACNA1C-E1115K missense mutation, identified in a RT patient with idiopathic QT prolongation, bradycardia, and autism spectrum RT disorder, converts the L-type calcium channel into a hybrid nonselective RT monovalent cation channel."; RL Heart Rhythm 16:270-278(2019). RN [45] 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). RN [46] RP VARIANTS NEDHLSS 161-ARG--LEU-2221 DEL; LEU-166; ARG-177; TRP-324; MET-403; RP 528-TRP--LEU-2221 DEL; ARG-601; THR-611; ARG-614; PRO-614; PHE-657; ILE-743 RP DEL; ALA-1187; VAL-1408; LEU-1411 AND 1989-ARG--LEU-2221 DEL, RP CHARACTERIZATION OF VARIANT NEDHLSS VAL-1408, AND FUNCTION. RX PubMed=34163037; DOI=10.1038/s41436-021-01232-8; RG Undiagnosed Diseases Network; RA Rodan L.H., Spillmann R.C., Kurata H.T., Lamothe S.M., Maghera J., RA Jamra R.A., Alkelai A., Antonarakis S.E., Atallah I., Bar-Yosef O., RA Bilan F., Bjorgo K., Blanc X., Van Bogaert P., Bolkier Y., Burrage L.C., RA Christ B.U., Granadillo J.L., Dickson P., Donald K.A., Dubourg C., RA Eliyahu A., Emrick L., Engleman K., Gonfiantini M.V., Good J.M., Kalser J., RA Kloeckner C., Lachmeijer G., Macchiaiolo M., Nicita F., Odent S., RA O'Heir E., Ortiz-Gonzalez X., Pacio-Miguez M., Palomares-Bralo M., Pena L., RA Platzer K., Quinodoz M., Ranza E., Rosenfeld J.A., Roulet-Perez E., RA Santani A., Santos-Simarro F., Pode-Shakked B., Skraban C., Slaugh R., RA Superti-Furga A., Thiffault I., van Jaabrsveld R.H., Vincent M., Wang H.G., RA Zacher P., Rush E., Pitt G.S., Au P.Y.B., Shashi V.; RT "Phenotypic expansion of CACNA1C-associated disorders to include isolated RT neurological manifestations."; RL Genet. Med. 23:1922-1932(2021). RN [47] RP ERRATUM OF PUBMED:34163037. RX PubMed=34522029; DOI=10.1038/s41436-021-01306-7; RG Undiagnosed Diseases Network; RA Rodan L.H., Spillmann R.C., Kurata H.T., Lamothe S.M., Maghera J., RA Jamra R.A., Alkelai A., Antonarakis S.E., Atallah I., Bar-Yosef O., RA Bilan F., Bjorgo K., Blanc X., Van Bogaert P., Bolkier Y., Burrage L.C., RA Christ B.U., Granadillo J.L., Dickson P., Donald K.A., Dubourg C., RA Eliyahu A., Emrick L., Engleman K., Gonfiantini M.V., Good J.M., Kalser J., RA Kloeckner C., Lachmeijer G., Macchiaiolo M., Nicita F., Odent S., RA O'Heir E., Ortiz-Gonzalez X., Pacio-Miguez M., Palomares-Bralo M., Pena L., RA Platzer K., Quinodoz M., Ranza E., Rosenfeld J.A., Roulet-Perez E., RA Santani A., Santos-Simarro F., Pode-Shakked B., Skraban C., Slaugh R., RA Superti-Furga A., Thiffault I., van Jaabrsveld R.H., Vincent M., Wang H.G., RA Zacher P., Rush E., Pitt G.S., Au P.Y.B., Shashi V.; RL Genet. Med. 23:2016-2016(2021). 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 PubMed:30023270, PubMed:30172029, PubMed:34163037). Mediates influx of CC calcium ions into the cytoplasm, and thereby triggers calcium release CC from the sarcoplasm (By similarity). Plays an important role in CC excitation-contraction coupling in the heart. Required for normal heart CC development and normal regulation of heart rhythm (PubMed:15454078, CC PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). CC Required for normal contraction of smooth muscle cells in blood vessels CC and in the intestine. Essential for normal blood pressure regulation CC via its role in the contraction of arterial smooth muscle cells CC (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the CC 'high-voltage activated' (HVA) group (Probable). CC {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:30023270, CC ECO:0000269|PubMed:30172029, ECO:0000269|PubMed:34163037, CC ECO:0000269|PubMed:7737988, ECO:0000269|PubMed:8099908, CC ECO:0000269|PubMed:8392192, ECO:0000269|PubMed:9013606, CC ECO:0000269|PubMed:9087614, 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, CC ECO:0000269|PubMed:30023270, ECO:0000269|PubMed:30172029}. 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 -!- DISEASE: Neurodevelopmental disorder with hypotonia, language delay, CC and skeletal defects with or without seizures (NEDHLSS) [MIM:620029]: CC An autosomal dominant disorder characterized by global developmental CC delay apparent from infancy, intellectual disability, poor or absent CC speech, behavioral abnormalities, and hypotonia with delayed walking or CC inability to walk. Additional features include epilepsy, mild skeletal CC defects, and non-specific dysmorphic features. CC {ECO:0000269|PubMed:30513141, ECO:0000269|PubMed:34163037}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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 CC (TC 1.A.1.11) family. CACNA1C subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA02500.2; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 CCDS; CCDS91636.1; -. [Q13936-19] DR CCDS; CCDS91637.1; -. [Q13936-35] 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 PDB; 7L8V; NMR; -; C=1662-1682. DR PDB; 8EOG; EM; 3.30 A; K=112-1658. DR PDB; 8EOI; EM; 3.40 A; K=109-1658. DR PDB; 8FD7; EM; 3.10 A; K=1-1696. DR PDB; 8WE6; EM; 2.90 A; A=1-2221. DR PDB; 8WE7; EM; 3.20 A; A=1-2221. DR PDB; 8WE8; EM; 2.90 A; A=1-2221. DR PDB; 8WE9; EM; 3.00 A; A=1-2221. DR PDB; 8WEA; EM; 3.20 A; A=1-2221. 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 PDBsum; 7L8V; -. DR PDBsum; 8EOG; -. DR PDBsum; 8EOI; -. DR PDBsum; 8FD7; -. DR PDBsum; 8WE6; -. DR PDBsum; 8WE7; -. DR PDBsum; 8WE8; -. DR PDBsum; 8WE9; -. DR PDBsum; 8WEA; -. DR AlphaFoldDB; Q13936; -. DR BMRB; Q13936; -. DR EMDB; EMD-25492; -. DR EMDB; EMD-25493; -. DR EMDB; EMD-28376; -. DR EMDB; EMD-29004; -. DR EMDB; EMD-32544; -. DR SMR; Q13936; -. DR BioGRID; 107229; 38. 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 GlyCosmos; Q13936; 4 sites, No reported glycans. 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; 9606-ENSP00000266376; -. DR PeptideAtlas; 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; 564 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; ENSG00000285479.3. [Q13936-29] DR Ensembl; ENST00000643038.2; ENSP00000494095.1; ENSG00000285479.3. [Q13936-11] DR Ensembl; ENST00000643138.1; ENSP00000496049.1; ENSG00000285479.3. [Q13936-22] DR Ensembl; ENST00000643701.1; ENSP00000496458.1; ENSG00000285479.3. [Q13936-15] DR Ensembl; ENST00000643858.1; ENSP00000495576.1; ENSG00000285479.3. [Q13936-14] DR Ensembl; ENST00000644048.1; ENSP00000494782.1; ENSG00000285479.3. [Q13936-31] DR Ensembl; ENST00000644235.2; ENSP00000494058.1; ENSG00000285479.3. [Q13936-12] DR Ensembl; ENST00000644369.2; ENSP00000494765.1; ENSG00000285479.3. [Q13936-23] DR Ensembl; ENST00000644660.1; ENSP00000496749.1; ENSG00000285479.3. [Q13936-20] DR Ensembl; ENST00000644691.1; ENSP00000494420.1; ENSG00000285479.3. [Q13936-30] DR Ensembl; ENST00000644891.1; ENSP00000496681.1; ENSG00000285479.3. [Q13936-32] DR Ensembl; ENST00000645584.1; ENSP00000494018.1; ENSG00000285479.3. [Q13936-24] DR Ensembl; ENST00000645965.1; ENSP00000493890.1; ENSG00000285479.3. [Q13936-27] DR Ensembl; ENST00000646257.1; ENSP00000493573.1; ENSG00000285479.3. [Q13936-21] DR Ensembl; ENST00000647062.1; ENSP00000495080.1; ENSG00000285479.3. [Q13936-13] DR Ensembl; ENST00000647327.2; ENSP00000493781.1; ENSG00000285479.3. [Q13936-37] DR Ensembl; ENST00000647521.1; ENSP00000495678.1; ENSG00000285479.3. [Q13936-25] DR Ensembl; ENST00000682686.1; ENSP00000507309.1; ENSG00000151067.23. [Q13936-19] DR Ensembl; ENST00000683482.1; ENSP00000507169.1; ENSG00000151067.23. [Q13936-35] DR Ensembl; ENST00000710479.1; ENSP00000518305.1; ENSG00000285479.3. [Q13936-35] DR Ensembl; ENST00000710487.1; ENSP00000518307.1; ENSG00000285479.3. [Q13936-19] 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 AGR; HGNC:1390; -. 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 MIM; 620029; phenotype. DR neXtProt; NX_Q13936; -. DR OpenTargets; ENSG00000151067; -. DR Orphanet; 595109; Atypical Timothy syndrome. DR Orphanet; 130; Brugada syndrome. DR Orphanet; 528084; Non-specific syndromic intellectual disability. DR Orphanet; 101016; Romano-Ward syndrome. DR Orphanet; 595098; Timothy syndrome type 1. DR Orphanet; 595105; Timothy syndrome type 2. DR PharmGKB; PA83; -. DR VEuPathDB; HostDB:ENSG00000151067; -. DR eggNOG; KOG2301; Eukaryota. DR GeneTree; ENSGT00940000156127; -. DR InParanoid; Q13936; -. DR OMA; DCCGDEN; -. DR OrthoDB; 1110761at2759; -. 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 1159 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 101 other cell types or tissues. DR ExpressionAtlas; Q13936; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:BHF-UCL. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. 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; 1.10.287.70; -; 4. DR Gene3D; 6.10.250.2180; -; 1. DR Gene3D; 6.10.250.2500; -; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 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 PANTHER; PTHR45628; VOLTAGE-DEPENDENT CALCIUM CHANNEL TYPE A SUBUNIT ALPHA-1; 1. DR PANTHER; PTHR45628:SF10; VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL SUBUNIT ALPHA-1C; 1. DR Pfam; PF08763; Ca_chan_IQ; 1. DR Pfam; PF16885; CAC1F_C; 1. 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. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 4. DR Genevisible; Q13936; HS. 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; Epilepsy; Glycoprotein; Host-virus interaction; KW Intellectual disability; Ion channel; Ion transport; Long QT syndrome; KW Membrane; Metal-binding; Phosphoprotein; Postsynaptic cell membrane; KW Reference proteome; Repeat; Synapse; Transmembrane; Transmembrane helix; KW 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; uncertain significance; increased FT 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; uncertain significance; affects FT 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 161..2221 FT /note="Missing (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087754" FT VARIANT 166 FT /note="F -> L (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087755" FT VARIANT 177 FT /note="K -> R (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087756" FT VARIANT 304 FT /note="I -> T" FT /evidence="ECO:0000269|PubMed:25633834" FT /id="VAR_075150" FT VARIANT 324 FT /note="R -> W (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087757" FT VARIANT 381 FT /note="P -> S (in LQT8; uncertain significance; no effect FT 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 403 FT /note="V -> M (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087758" 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; uncertain significance; no effect FT on channel activity)" FT /evidence="ECO:0000269|PubMed:24728418" FT /id="VAR_075152" FT VARIANT 477 FT /note="E -> K (in LQT8; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25633834" FT /id="VAR_075153" FT VARIANT 490 FT /note="G -> R (in BRGDA3; uncertain significance; affects FT 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 528..2221 FT /note="Missing (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087759" 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 601 FT /note="L -> R (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087760" FT VARIANT 611 FT /note="M -> T (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087761" FT VARIANT 614 FT /note="L -> P (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087762" FT VARIANT 614 FT /note="L -> R (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087763" FT VARIANT 643 FT /note="S -> F (in TS; affects voltage-gated calcium channel FT activity resulting in a marked decrease in peak currents FT and increased late currents)" FT /evidence="ECO:0000269|PubMed:30023270" FT /id="VAR_087764" FT VARIANT 657 FT /note="L -> F (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087765" FT VARIANT 743 FT /note="Missing (in NEDHLSS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087766" 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; uncertain 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; uncertain significance; FT results in reduced whole-cell calcium 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 1135 FT /note="E -> K (in TS; affects voltage-gated calcium channel FT activity resulting in loss of calcium selectivity; mutant FT channels show a marked increase in sodium-mediated inward FT currents and potassium-mediated outward currents)" FT /evidence="ECO:0000269|PubMed:30172029" FT /id="VAR_087767" FT VARIANT 1159 FT /note="R -> H (found in a patient with autism; uncertain FT 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 1187 FT /note="V -> A (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087768" FT VARIANT 1365 FT /note="A -> T (in LQT8; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25633834" FT /id="VAR_075161" FT VARIANT 1408 FT /note="L -> V (in NEDHLSS; affects voltage-gated calcium FT channel activity resulting in decreased current density FT when expressed in a heterologous system)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087769" FT VARIANT 1411 FT /note="V -> L (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087770" FT VARIANT 1411 FT /note="V -> M (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:30513141" FT /id="VAR_087771" 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; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25633834" FT /id="VAR_075166" FT VARIANT 1800 FT /note="T -> I (in LQT8; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25633834" FT /id="VAR_075167" FT VARIANT 1831 FT /note="G -> C (in LQT8; uncertain significance; no effect FT 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; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25633834" FT /id="VAR_075171" FT VARIANT 1953 FT /note="T -> M (in LQT8; uncertain 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..2221 FT /note="Missing (in NEDHLSS)" FT /evidence="ECO:0000269|PubMed:34163037" FT /id="VAR_087772" FT VARIANT 1989 FT /note="R -> Q (in LQT8; uncertain 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; uncertain 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; uncertain significance; FT results in increased whole-cell calcium currents)" FT /evidence="ECO:0000269|PubMed:27218670" FT /id="VAR_076415" FT VARIANT 2097 FT /note="V -> I (in LQT8; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25633834" FT /id="VAR_075176" FT VARIANT 2122 FT /note="A -> G (in LQT8; uncertain 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; FT CAA84340/CAA84341/CAA84342/CAA84343/CAA84344/CAA84345/CAA84346/CAA84347/CAA84348/CAA84349/CAA84350/CAA84351, FT 7; CAA12174 and 9; AAX37354/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 113..119 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 124..143 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 156..181 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 185..187 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 189..210 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 235..242 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 243..250 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 251..254 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 255..265 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 266..268 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 269..289 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 291..294 FT /evidence="ECO:0007829|PDB:8EOI" FT STRAND 299..303 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 305..307 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 315..317 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 327..329 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 338..342 FT /evidence="ECO:0007829|PDB:8EOI" FT STRAND 346..349 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 350..360 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 365..376 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 381..412 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 413..419 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 429..443 FT /evidence="ECO:0007829|PDB:5V2Q" FT TURN 521..525 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 526..541 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 553..577 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 580..584 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 585..589 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 590..605 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 606..608 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 614..630 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 635..637 FT /evidence="ECO:0007829|PDB:8EOI" FT HELIX 638..672 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 689..691 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 692..704 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 709..718 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 720..723 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 724..727 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 730..762 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 891..897 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 901..918 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 929..933 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 954..970 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 977..981 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 988..999 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1005..1008 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 1009..1016 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1017..1019 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1023..1028 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1038..1049 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1051..1070 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1071..1073 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1076..1082 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 1086..1088 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1091..1095 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1099..1102 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1105..1108 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1111..1113 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1119..1124 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1125..1132 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1133..1136 FT /evidence="ECO:0007829|PDB:8EOI" FT HELIX 1137..1145 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 1149..1151 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1156..1158 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1163..1190 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 1191..1194 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1195..1198 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1204..1212 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1213..1215 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 1227..1229 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 1231..1234 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 1236..1238 FT /evidence="ECO:0007829|PDB:8EOI" FT HELIX 1239..1255 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1256..1259 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1265..1290 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1330..1348 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 1371..1374 FT /evidence="ECO:0007829|PDB:8EOI" FT TURN 1375..1378 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1379..1382 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1383..1385 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1386..1390 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1393..1402 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1408..1429 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1437..1440 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1443..1445 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1447..1449 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1450..1462 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1466..1472 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1473..1476 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1489..1491 FT /evidence="ECO:0007829|PDB:8EOI" FT HELIX 1500..1530 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1534..1537 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1539..1551 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1552..1555 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1558..1560 FT /evidence="ECO:0007829|PDB:8EOI" FT HELIX 1562..1565 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1568..1570 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 1574..1576 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1580..1586 FT /evidence="ECO:0007829|PDB:8FD7" FT HELIX 1588..1590 FT /evidence="ECO:0007829|PDB:8FD7" FT TURN 1591..1593 FT /evidence="ECO:0007829|PDB:8FD7" FT STRAND 1599..1602 FT /evidence="ECO:0007829|PDB:8EOI" FT HELIX 1609..1651 FT /evidence="ECO:0007829|PDB:3G43" FT TURN 1654..1656 FT /evidence="ECO:0007829|PDB:8EOI" 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 //