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voltage-dependent Ca+2 channel alpha-1C (Ca+2 channel L type alpha-1 polypeptide isoform 1, cardiac muscle, Cav1.2, CACNA1C, CACNL1A1, CCHL1A1, CACH2, CACN2)

Dihydropyridine-sensitive, long-acting L-type Ca+2 currents Function: - pore-forming & voltage-sensitive alpha-1 subunit of voltage-sensitive Ca+2 channel - alpha-1C gives rise to L-type Ca+2 currents; a) long-lasting (L-type) Ca+2 channels belong to the 'high-voltage activated' (HVA) group b) blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, & by omega-agatoxin-IIIA (omega-Aga-IIIA) c) insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) & omega-agatoxin-IVA (omega-Aga-IVA) - Ca+2 channels containing the alpha-1C subunit play a role in excitation-contraction coupling in the heart - the various isoforms display marked differences in the sensitivity to dihydropyridines - phosphorylation by PKA activates the channel (putative) Structure: - each of the 4 internal repeats contains 5 hydrophobic transmembrane segments (S1, S2, S3, S5, S6) & one positively charged transmembrane segment (S4) - S4 segments probably represent the voltage-sensor; they are characterized by a series of positively charged amino acids at every third position - binding of intracellular Ca+2 through the EF-hand motif inhibits the opening of the channel (putative) - belongs to the Ca+2 channel alpha-1 subunit (TC 1.A.1.11) family Compartment: membrane Alternative splicing: named isoforms=35 Expression: - expressed in brain, heart, jejunum, ovary, pancreatic beta-cells & vascular smooth muscle Pathology: - expression is reduced in atherosclerotic vascular smooth muscle - defects in CACNA1C are the cause of a) Timothy syndrome b) Brugada syndrome type 3 - variations in CACNA1C may be associated with: - autism, ADHD, bipolar disorder, depression, &/or schizophrenia [3] (abstract does not specify which)

Related

anti-Vgcc antibody voltage-dependent Ca+2 channel

General

voltage-dependent Ca+2 channel alpha-1

Properties

SIZE: MW = 249 kD entity length = 2221 aa COMPARTMENT: cellular membrane MOTIF: cytoplasmic domain {1-124} transmembrane domain {125-143} exoplasmic loop {144-160} MOTIF: N-glycosylation site {N153} transmembrane domain {161-181} cytoplasmic loop {182-193} transmembrane domain {194-212} exoplasmic loop {213-232} transmembrane domain {233-251} cytoplasmic loop {252-270} transmembrane domain {271-290} exoplasmic loop {291-380} MOTIF: N-glycosylation site {N328} transmembrane domain {381-405} cytoplasmic loop {406-524} MOTIF: BINDING TO BETA SUBUNIT {428-445} transmembrane domain {525-543} exoplasmic loop {544-558} transmembrane domain {559-578} cytoplasmic loop {579-586} transmembrane domain {587-605} exoplasmic loop {606-615} transmembrane domain {616-634} cytoplasmic loop {635-653} transmembrane domain {654-673} MOTIF: leucine residue {654-660} (7) exoplasmic loop {674-728} transmembrane domain {729-753} cytoplasmic loop {754-900} MOTIF: glutamate residue {768-774} (7) transmembrane domain {901-919} exoplasmic loop {920-935} transmembrane domain {936-955} cytoplasmic loop {956-987} transmembrane domain {988-1006} exoplasmic loop {1007-1013} transmembrane domain {1014-1032} cytoplasmic loop {1033-1051} transmembrane domain {1052-1071} exoplasmic loop {1072-1161} transmembrane domain {1162-1186} MOTIF: isoleucine residue {1167-1173} (7) cytoplasmic loop {1187-1239} transmembrane domain {1240-1258} exoplasmic loop {1259-1273} transmembrane domain {1274-1293} cytoplasmic loop {1294-1301} transmembrane domain {1302-1320} exoplasmic loop {1321-1372} transmembrane domain {1373-1391} cytoplasmic loop {1392-1410} transmembrane domain {1411-1430} exoplasmic loop {1431-1499} MOTIF: N-glycosylation site {N1436} N-glycosylation site {N1487} transmembrane domain {1500-1524} cytoplasmic domain {1525-2221} MOTIF: Ser phosphorylation site {S1535} Ca+2-binding site SITE: 1553-1564 Ser phosphorylation site {S1973} Ser phosphorylation site {S1981} glycine-rich region {2084-2087}

Database Correlations

OMIM correlations MORBIDMAP 114205 UniProt Q13936 PFAM correlations Entrez Gene 775 Kegg hsa:775

References

  1. UniProt :accession Q13936
  2. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=CACNA1C
  3. Cross-Disorder Group of the Psychiatric Genomics Consortium Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet, Early Online Publication, 28 February 2013 PMID: 23453885 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)62129-1/abstract