[1]
|
NUCLEOTIDE SEQUENCE (ISOFORM 1), AND ALTERNATIVE SPLICING.
TISSUE=Fetal fibroblast;
PubMed=1316612 [NCBI, ExPASy, EBI, Israel, Japan]
Soldatov N.M.;
"Molecular diversity of L-type Ca2+ channel transcripts in human fibroblasts.";
Proc. Natl. Acad. Sci. U.S.A. 89:4628-4632(1992).
|
[2]
|
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 18), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1822-1863, FUNCTION, TISSUE SPECIFICITY, AND VARIANT ARG-84.
TISSUE=Heart;
PubMed=8392192 [NCBI, ExPASy, EBI, Israel, Japan]
Schultz D.,
Mikala G.,
Yatani A.,
Engle D.B.,
Iles D.E.,
Segers B.,
Sinke R.J.,
Weghuis D.O.,
Kloeckner U.,
Wakamori M.,
Wang J.-J.,
Melvin D.,
Varadi G.,
Schwartz A.;
"Cloning, chromosomal localization, and functional expression of the alpha1 subunit of the L-type voltage-dependent calcium channel from normal human heart.";
Proc. Natl. Acad. Sci. U.S.A. 90:6228-6232(1993).
|
[3]
|
NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 1112-1803 (ISOFORMS 24/27), AND NUCLEOTIDE SEQUENCE [MRNA] OF 1364-1972 (ISOFORMS 11/12/19/20/21/22/23/30/31/32).
TISSUE=Hippocampus, and Lung fibroblast;
DOI=10.1006/geno.1994.1347; PubMed=7959794 [NCBI, ExPASy, EBI, Israel, Japan]
Soldatov N.M.;
"Genomic structure of human L-type Ca2+ channel.";
Genomics 22:77-87(1994).
|
[4]
|
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 12; 19 AND 20), ALTERNATIVE SPLICING, FUNCTION, AND MUTAGENESIS OF GLY-954 AND TYR-958.
TISSUE=Fibroblast;
DOI=10.1074/jbc.270.18.10540; PubMed=7737988 [NCBI, ExPASy, EBI, Israel, Japan]
Soldatov N.M.,
Bouron A.,
Reuter H.;
"Different voltage-dependent inhibition by dihydropyridines of human Ca2+ channel splice variants.";
J. Biol. Chem. 270:10540-10543(1995).
|
[5]
|
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 16 AND 17), ALTERNATIVE SPLICING, AND VARIANT ARG-84.
TISSUE=Heart;
PubMed=9087614 [NCBI, ExPASy, EBI, Israel, Japan]
Kloeckner U.,
Mikala G.,
Eisfeld J.,
Iles D.E.,
Strobeck M.,
Mershon J.L.,
Schwartz A.,
Varadi G.;
"Properties of three COOH-terminal splice variants of a human cardiac L-type Ca2+-channel alpha1-subunit.";
Am. J. Physiol. 272:H1372-H1381(1997).
|
[6]
|
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 26 AND 27), ALTERNATIVE SPLICING, AND FUNCTION.
TISSUE=Hippocampus;
DOI=10.1074/jbc.272.6.3560; PubMed=9013606 [NCBI, ExPASy, EBI, Israel, Japan]
Soldatov N.M.,
Zuelke R.D.,
Bouron A.,
Reuter H.;
"Molecular structures involved in L-type calcium channel inactivation. Role of the carboxyl-terminal region encoded by exons 40-42 in alpha1C subunit in the kinetics and Ca2+ dependence of inactivation.";
J. Biol. Chem. 272:3560-3566(1997).
|
[7]
|
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 21; 22 AND 23), AND FUNCTION.
DOI=10.1016/S0014-5793(98)00425-6; PubMed=9607315 [NCBI, ExPASy, EBI, Israel, Japan]
Zuehlke R.D.,
Bouron A.,
Soldatov N.M.,
Reuter H.;
"Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human alpha1C subunit gene.";
FEBS Lett. 427:220-224(1998).
|
[8]
|
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12), FUNCTION, AND TISSUE SPECIFICITY.
TISSUE=Intestinal smooth muscle;
DOI=10.1152/ajpcell.00140.2002; PubMed=12176756 [NCBI, ExPASy, EBI, Israel, Japan]
Lyford G.L.,
Strege P.R.,
Shepard A.,
Ou Y.,
Ermilov L.,
Miller S.M.,
Gibbons S.J.,
Rae J.L.,
Szurszewski J.H.,
Farrugia G.;
"alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation.";
Am. J. Physiol. 283:C1001-C1008(2002).
|
[9]
|
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 13; 14; 15; 24 AND 25), FUNCTION, AND TISSUE SPECIFICITY.
DOI=10.1073/pnas.0606539103; PubMed=17071743 [NCBI, ExPASy, EBI, Israel, Japan]
Tiwari S.,
Zhang Y.,
Heller J.,
Abernethy D.R.,
Soldatov N.M.;
"Atherosclerosis-related molecular alteration of the human CaV1.2 calcium channel alpha1C subunit.";
Proc. Natl. Acad. Sci. U.S.A. 103:17024-17029(2006).
|
[10]
|
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 11; 28; 29; 30; 31; 32 AND 33), ALTERNATIVE SPLICING, AND VARIANT ARG-84.
Soldatov N.;
"Functional expression of splice variants of human l-type calcium channel (isoform 1 gene).";
Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
|
[11]
|
NUCLEOTIDE SEQUENCE [MRNA] OF 1-180 (ISOFORM 34).
DOI=10.1074/jbc.C100642200; PubMed=11741969 [NCBI, ExPASy, EBI, Israel, Japan]
Blumenstein Y.,
Kanevsky N.,
Sahar G.,
Barzilai R.,
Ivanina T.,
Dascal N.;
"A novel long N-terminal isoform of human L-type Ca2+ channel is up-regulated by protein kinase C.";
J. Biol. Chem. 277:3419-3423(2002).
|
[12]
|
NUCLEOTIDE SEQUENCE [MRNA] OF 1182-1503 (ISOFORMS 6/12/20/23/24), AND NUCLEOTIDE SEQUENCE [MRNA] OF 1182-1503 (ISOFORMS 7/13/16/17/18/21/22).
TISSUE=Heart;
PubMed=2173707 [NCBI, ExPASy, EBI, Israel, Japan]
Perez-Reyes E.,
Wei X.,
Castellano A.,
Birnbaumer L.;
"Molecular diversity of L-type calcium channels. Evidence for alternative splicing of the transcripts of three non-allelic genes.";
J. Biol. Chem. 265:20430-20436(1990).
|
[13]
|
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1140-1206.
TISSUE=Heart;
DOI=10.1016/0888-7543(91)90471-P; PubMed=1653763 [NCBI, ExPASy, EBI, Israel, Japan]
Powers P.A.,
Gregg R.G.,
Lalley P.A.,
Liao M.,
Hogan K.;
"Assignment of the human gene for the alpha 1 subunit of the cardiac DHP-sensitive Ca2+ channel (CCHL1A1) to chromosome 12p12-pter.";
Genomics 10:835-839(1991).
|
[14]
|
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1196-1421.
TISSUE=Brain;
DOI=10.1016/S0888-7543(05)80135-1; PubMed=1335957 [NCBI, ExPASy, EBI, Israel, Japan]
Sun W.,
McPherson J.D.,
Hoang D.Q.,
Wasmuth J.J.,
Evans G.A.,
Montal M.;
"Mapping of a human brain voltage-gated calcium channel to human chromosome 12p13-pter.";
Genomics 14:1092-1094(1992).
|
[15]
|
MUTAGENESIS, AND CALCIUM-BINDING.
PubMed=8099908 [NCBI, ExPASy, EBI, Israel, Japan]
Tang S.,
Mikala G.,
Bahinski A.,
Yatani A.,
Varadi G.,
Schwartz A.;
"Molecular localization of ion selectivity sites within the pore of a human L-type cardiac calcium channel.";
J. Biol. Chem. 268:13026-13029(1993).
|
[16]
|
INTERACTION WITH CACNA2D4.
DOI=10.1124/mol.62.3.485; PubMed=12181424 [NCBI, ExPASy, EBI, Israel, Japan]
Qin N.,
Yagel S.,
Momplaisir M.-L.,
Codd E.E.,
D'Andrea M.R.;
"Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit.";
Mol. Pharmacol. 62:485-496(2002).
|
[17]
|
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 428-445 IN COMPLEX WITH CACNB2.
DOI=10.1038/nature02588; PubMed=15141227 [NCBI, ExPASy, EBI, Israel, Japan]
Van Petegem F.,
Clark K.A.,
Chatelain F.C.,
Minor D.L. Jr.;
"Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.";
Nature 429:671-675(2004).
|
[18]
|
VARIANT TS ARG-406, AND CHARACTERIZATION OF VARIANT TS ARG-406.
DOI=10.1016/j.cell.2004.09.011; PubMed=15454078 [NCBI, ExPASy, EBI, Israel, Japan]
Splawski I.,
Timothy K.W.,
Sharpe L.M.,
Decher N.,
Kumar P.,
Bloise R.,
Napolitano C.,
Schwartz P.J.,
Joseph R.M.,
Condouris K.,
Tager-Flusberg H.,
Priori S.G.,
Sanguinetti M.C.,
Keating M.T.;
"Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.";
Cell 119:19-31(2004).
|
[19]
|
VARIANT TS SER-402.
DOI=10.1073/pnas.0502506102; PubMed=15863612 [NCBI, ExPASy, EBI, Israel, Japan]
Splawski I.,
Timothy K.W.,
Decher N.,
Kumar P.,
Sachse F.B.,
Beggs A.H.,
Sanguinetti M.C.,
Keating M.T.;
"Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.";
Proc. Natl. Acad. Sci. U.S.A. 102:8089-8096(2005).
|
[20]
|
VARIANTS BRS3 VAL-39 AND ARG-490, AND CHARACTERIZATION OF VARIANTS BRS3 VAL-39 AND ARG-490.
DOI=10.1161/CIRCULATIONAHA.106.668392; PubMed=17224476 [NCBI, ExPASy, EBI, Israel, Japan]
Antzelevitch C.,
Pollevick G.D.,
Cordeiro J.M.,
Casis O.,
Sanguinetti M.C.,
Aizawa Y.,
Guerchicoff A.,
Pfeiffer R.,
Oliva A.,
Wollnik B.,
Gelber P.,
Bonaros E.P. Jr.,
Burashnikov E.,
Wu Y.,
Sargent J.D.,
Schickel S.,
Oberheiden R.,
Bhatia A.,
Hsu L.F., ![]()
Haissaguerre M.,
Schimpf R.,
Borggrefe M.,
Wolpert C.;
"Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death.";
Circulation 115:442-449(2007).
|
|
- FUNCTION: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds.
- SUBUNIT: Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity. Interacts with CACNA2D4.
- INTERACTION:
Q9NZU7:CABP1; NbExp=2; IntAct=EBI-1038838, EBI-907894;
P62158:CALM1; NbExp=1; IntAct=EBI-1038838, EBI-397435;
- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
- ALTERNATIVE PRODUCTS:
34 named isoforms [FASTA] produced by alternative splicing. Additional isoforms seem to exist. Exons 8A, 21, 22, 31, 32, 33, 40B, 43A, 41A and 45 are alternatively spliced in a variety of combinations. Experimental confirmation may be lacking for some isoforms.
|
| Name | 2 |
| Isoform ID | Q13936-2 |
| Features which should be applied to build the isoform sequence: VSP_000894. |
|
|
| Name | 3 |
| Isoform ID | Q13936-3 |
| Note: Contains exon 8a. |
| Features which should be applied to build the isoform sequence: VSP_000886. |
|
|
| Name | 4 |
| Isoform ID | Q13936-4 |
| Note: Lacks exon 21. |
| Features which should be applied to build the isoform sequence: VSP_000887. |
|
|
| Name | 5 |
| Isoform ID | Q13936-5 |
| Note: Lacks exon 22. |
| Features which should be applied to build the isoform sequence: VSP_000888. |
|
|
| Name | 6 |
| Isoform ID | Q13936-6 |
| Note: Lacks exon 31. |
| Features which should be applied to build the isoform sequence: VSP_000889. |
|
|
| Name | 7 |
| Isoform ID | Q13936-7 |
| Note: Lacks exon 32. |
| Features which should be applied to build the isoform sequence: VSP_000890. |
|
|
| Name | 8 |
| Isoform ID | Q13936-8 |
| Note: Lacks exon 33. |
| Features which should be applied to build the isoform sequence: VSP_000891. |
|
|
| Name | 9 |
| Isoform ID | Q13936-9 |
| Note: Contains exon 40B and 43A. |
| Features which should be applied to build the isoform sequence: VSP_000892. |
|
|
| Name | 10 |
| Isoform ID | Q13936-10 |
| Note: Contains exon 41A. |
| Features which should be applied to build the isoform sequence: VSP_000893. |
|
|
| Name | 11 |
| Synonyms | Alpha-1C.90 |
| Isoform ID | Q13936-11 |
| Note: Lacks exon 45. |
| Features which should be applied to build the isoform sequence: VSP_000895. |
|
| | | | | | | | |
| Name | 20 |
| Synonyms | Alpha-1C.77 |
| Isoform ID | Q13936-20 |
| Note: Predominant isoform in atherosclerotic vascular smooth muscle cells. |
| Features which should be applied to build the isoform sequence: VSP_000887, VSP_000889, VSP_000895. |
|
| | | | | | | | | | | | | |
| Name | 34 |
| Synonyms | Alpha-1C,long-NT |
| Isoform ID | Q13936-34 |
| Note: Enhanced by PKC activator. |
| Features which should be applied to build the isoform sequence: VSP_035146. |
|
|
- TISSUE SPECIFICITY: Expressed in brain, heart, jejunum, ovary, pancreatic beta-cells and vascular smooth muscle. Overall expression is reduced in atherosclerotic vascular smooth muscle.
- DOMAIN: Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.
- DOMAIN: Binding of intracellular calcium through the EF-hand motif inhibits the opening of the channel (By similarity).
- PTM: Phosphorylation by PKA activates the channel (By similarity).
- DISEASE: Defects in CACNA1C are the cause of Timothy syndrome (TS) [MIM:601005]. TS is a disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities and autism.
- DISEASE: Defects in CACNA1C are the cause of Brugada syndrome type 3 (BRS3) [MIM:611875]. BRS3 is a heart disease characterized by the association of Brugada syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset.
- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family [view classification].
- SEQUENCE CAUTION:
- Sequence=AAA02500.2; Type=Frameshift; Positions=1845;
- WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=CACNA1C";.
|
ExPASy Home page
