MGP Database

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MGP000381

UniProt Annotations

Entry Information
Gene Namecalcium channel, voltage-dependent, L type, alpha 1C subunit
Protein EntryCAC1C_HUMAN
UniProt IDQ13936
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=37; Comment=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=1; Synonyms=HFCC, Fibroblast; IsoId=Q13936-1; Sequence=Displayed; Name=2; IsoId=Q13936-2; Sequence=VSP_000894; Name=3; IsoId=Q13936-3; Sequence=VSP_000886; Note=Contains exon 8a.; Name=4; IsoId=Q13936-4; Sequence=VSP_000887; Note=Lacks exon 21.; Name=5; IsoId=Q13936-5; Sequence=VSP_000888; Note=Lacks exon 22.; Name=6; IsoId=Q13936-6; Sequence=VSP_000889; Note=Lacks exon 31.; Name=7; IsoId=Q13936-7; Sequence=VSP_000890; Note=Lacks exon 32.; Name=8; IsoId=Q13936-8; Sequence=VSP_000891; Note=Lacks exon 33.; Name=9; IsoId=Q13936-9; Sequence=VSP_000892; Note=Contains exon 40B and 43A.; Name=10; IsoId=Q13936-10; Sequence=VSP_000893; Note=Contains exon 41A.; Name=11; Synonyms=Alpha-1C.90; IsoId=Q13936-11; Sequence=VSP_000895; Note=Lacks exon 45.; Name=12; Synonyms=Alpha-1C.70; IsoId=Q13936-12; Sequence=VSP_000888, VSP_000889, VSP_000895; Name=13; Synonyms=Alpha-1C.127; IsoId=Q13936-13; Sequence=VSP_000888, VSP_000890, VSP_000893, VSP_000895; Name=14; Synonyms=Alpha-1C.126; IsoId=Q13936-14; Sequence=VSP_000888, VSP_000889, VSP_022504, VSP_000893, VSP_000895; Name=15; Synonyms=Alpha-1C.125; IsoId=Q13936-15; Sequence=VSP_000888, VSP_000889, VSP_022503, VSP_000893, VSP_000895; Name=16; IsoId=Q13936-16; Sequence=VSP_000885, VSP_000886, VSP_000888, VSP_000890; Name=17; IsoId=Q13936-17; Sequence=VSP_000885, VSP_000886, VSP_000888, VSP_000890, VSP_000895; Name=18; Synonyms=HHT-1; IsoId=Q13936-18; Sequence=VSP_000885, VSP_000886, VSP_000888, VSP_000890, VSP_000894; Name=19; Synonyms=Alpha-1C.76; IsoId=Q13936-19; Sequence=VSP_000887, VSP_000889, VSP_000891, VSP_000895; Name=20; Synonyms=Alpha-1C.77; IsoId=Q13936-20; Sequence=VSP_000887, VSP_000889, VSP_000895; Note=Predominant isoform in atherosclerotic vascular smooth muscle cells.; Name=21; Synonyms=Alpha-1C.69; IsoId=Q13936-21; Sequence=VSP_000887, VSP_000890, VSP_000895; Name=22; Synonyms=Alpha-1C.78; IsoId=Q13936-22; Sequence=VSP_000888, VSP_000890, VSP_000895; Name=23; Synonyms=Alpha-1C.105; IsoId=Q13936-23; Sequence=VSP_000886, VSP_000887, VSP_000889, VSP_000895; Name=24; Synonyms=Alpha-1C.71; IsoId=Q13936-24; Sequence=VSP_000888, VSP_000889, VSP_000893, VSP_000895; Name=25; Synonyms=Alpha-1C.73; IsoId=Q13936-25; Sequence=VSP_000888, VSP_000889, VSP_000891, VSP_000893, VSP_000895; Name=26; Synonyms=Alpha-1C.86; IsoId=Q13936-26; Sequence=VSP_000887, VSP_000889, VSP_000892, VSP_000895; Note=Not inhibited by calcium. Ref.3 (CAA84348) sequence is in conflict in position: 1573:A->T. {ECO:0000305}; Name=27; Synonyms=Alpha-1C.72; IsoId=Q13936-27; Sequence=VSP_000887, VSP_000889, VSP_000893, VSP_000895; Name=28; IsoId=Q13936-28; Sequence=VSP_000885, VSP_000886, VSP_000888, VSP_000889, VSP_000891, VSP_000894; Name=29; Synonyms=Alpha-1C.74; IsoId=Q13936-29; Sequence=VSP_000887, VSP_000889, VSP_000891, VSP_000893, VSP_000895; Name=30; Synonyms=Alpha-1C.87; IsoId=Q13936-30; Sequence=VSP_000889, VSP_000895; Name=31; Synonyms=Alpha-1C.88; IsoId=Q13936-31; Sequence=VSP_000888, VSP_000895; Name=32; Synonyms=Alpha-1C.89; IsoId=Q13936-32; Sequence=VSP_000887, VSP_000891, VSP_000895; Name=33; Synonyms=Alpha-1C.85; IsoId=Q13936-33; Sequence=VSP_000887, VSP_000889; Name=34; Synonyms=Alpha-1C,long-NT; IsoId=Q13936-34; Sequence=VSP_035146; Note=Enhanced by PKC activator.; Name=35; IsoId=Q13936-35; Sequence=VSP_035877, VSP_000888, VSP_000890, VSP_000895; Name=36; IsoId=Q13936-36; Sequence=VSP_000886, VSP_000888, VSP_000890; Note=Gene prediction based on EST data.; Name=37; IsoId=Q13936-37; Sequence=VSP_000886, VSP_000888, VSP_000890, VSP_000895; Note=Gene prediction based on EST data.;
DiseaseBrugada syndrome 3 (BRGDA3) [MIM:611875]: 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, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:17224476}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseTimothy syndrome (TS) [MIM:601005]: Disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities and autism. {ECO:0000269|PubMed:15454078, ECO:0000269|PubMed:15863612}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainBinding of intracellular calcium through the EF-hand motif inhibits the opening of the channel. {ECO:0000250}.
DomainEach 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.
FunctionVoltage-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. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function. {ECO:0000269|PubMed:12176756, ECO:0000269|PubMed:17071743, ECO:0000269|PubMed:7737988, ECO:0000269|PubMed:8392192, ECO:0000269|PubMed:9013606, ECO:0000269|PubMed:9607315}.
InteractionQ9NZU7:CABP1; NbExp=4; IntAct=EBI-1038838, EBI-907894; P62158:CALM3; NbExp=12; IntAct=EBI-1038838, EBI-397435;
PtmPhosphorylation by PKA activates the channel. {ECO:0000250}.
Sequence CautionSequence=AAA02500.2; Type=Frameshift; Positions=1844; Evidence={ECO:0000305};
SimilarityBelongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily. {ECO:0000305}.
Subcellular LocationMembrane; Multi-pass membrane protein. Cell membrane {ECO:0000250}. Note=The interaction between RRAD and CACNB2 regulates its trafficking to the cell membrane. {ECO:0000250}.
SubunitVoltage-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. Interacts (via the N-terminus and the C- terminal C and IQ motifs) with CABP1. The binding via the C motif is calcium independent whereas the binding via IQ requires the presence of calcium and is mutually exclusive with calmodulin binding. The binding to the cytoplasmic N-terminal domain is calcium independent but is essential for the channel modulation. Interacts (via C-terminal CDB motif) with CABP5; in a calcium- dependent manner (By similarity). Interacts with CIB1; the interaction increases upon cardiomyocytes hypertrophy (By similarity). {ECO:0000250}.
Tissue SpecificityExpressed in brain, heart, jejunum, ovary, pancreatic beta-cells and vascular smooth muscle. Overall expression is reduced in atherosclerotic vascular smooth muscle. {ECO:0000269|PubMed:12176756, ECO:0000269|PubMed:17071743, ECO:0000269|PubMed:8392192}.
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