Human Gene CACNA1C (ENST00000347598.9) Description and Page Index
Description: Homo sapiens calcium voltage-gated channel subunit alpha1 C (CACNA1C), transcript variant 1, mRNA. (from RefSeq NM_199460) RefSeq Summary (NM_001129827): This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]. Gencode Transcript: ENST00000347598.9 Gencode Gene: ENSG00000151067.22 Transcript (Including UTRs) Position: hg38 chr12:2,052,987-2,697,950 Size: 644,964 Total Exon Count: 49 Strand: + Coding Region Position: hg38 chr12:2,053,563-2,691,199 Size: 637,637 Coding Exon Count: 49
ID:CAC1C_HUMAN DESCRIPTION: RecName: Full=Voltage-dependent L-type calcium channel subunit alpha-1C; AltName: Full=Calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle; AltName: Full=Voltage-gated calcium channel subunit alpha Cav1.2; 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. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function. 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. 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). INTERACTION: Q9NZU7:CABP1; NbExp=4; IntAct=EBI-1038838, EBI-907894; P62158:CALM3; NbExp=2; IntAct=EBI-1038838, EBI-397435; SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Cell membrane (By similarity). Note=The interaction between RRAD and CACNB2 regulates its trafficking to the cell membrane (By similarity). 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 (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 (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. CACNA1C subfamily. SEQUENCE CAUTION: Sequence=AAA02500.2; Type=Frameshift; Positions=1844; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CACNA1C";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13936
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002520 immune system development GO:0006811 ion transport GO:0006816 calcium ion transport GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0007507 heart development GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion GO:0034765 regulation of ion transmembrane transport GO:0035115 embryonic forelimb morphogenesis GO:0035585 calcium-mediated signaling using extracellular calcium source GO:0043010 camera-type eye development GO:0050796 regulation of insulin secretion GO:0055085 transmembrane transport GO:0060402 calcium ion transport into cytosol GO:0061337 cardiac conduction GO:0061577 calcium ion transmembrane transport via high voltage-gated calcium channel GO:0070588 calcium ion transmembrane transport GO:0086002 cardiac muscle cell action potential involved in contraction GO:0086012 membrane depolarization during cardiac muscle cell action potential GO:0086045 membrane depolarization during AV node cell action potential GO:0086064 cell communication by electrical coupling involved in cardiac conduction GO:0086091 regulation of heart rate by cardiac conduction GO:0098911 regulation of ventricular cardiac muscle cell action potential GO:0098912 membrane depolarization during atrial cardiac muscle cell action potential