Voltage-dependent L-type calcium channel subunit alpha-1C

UniProt Q13936 Organism Homo sapiens Gene CACH2, CACN2, CACNA1C, CACNL1A1, CCHL1A1

Also known as: CACH2, CACN2, CACNA1C, CACNL1A1, CCHL1A1

Function

Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm. Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable).

Classification

Family (Pfam): PF08763 Ca_chan_IQ, PF16885 CAC1F_C, PF16905 GPHH, PF00520 Ion_trans
InterPro: CAC1F_C, GPHH_dom, Ion_trans_dom, VDCC_a1su_IQ, VDCC_alpha-1_subunit, VDCC_L_a1csu, VDCC_L_a1su, VDCCAlpha1, Volt_channel_dom_sf
Functional cluster: Membrane Transporters & GPCRs

Experimental structures · PDB · 32

1T0J X-ray 2.00A
2BE6 X-ray 2.00A
2F3Y X-ray 1.45A
2F3Z X-ray 1.60A
2LQC NMR
3G43 X-ray 2.10A
3OXQ X-ray 2.55A
5V2P X-ray 2.00A
5V2Q X-ray 1.70A
6C0A NMR
6DAD X-ray 1.65A
6DAE X-ray 2.00A
… and 20 more

A predicted model is available from AlphaFold.

Gene Ontology · 37

Disease associations

Timothy syndrome MONDO:0010979
Brugada syndrome 3 MONDO:0012742
long QT syndrome 8 MONDO:0032756
neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures MONDO:0859286

Drugs targeting this protein · 36

Neighborhood · nearest proteins

Nearest neighbours of Voltage-dependent L-type calcium channel subunit alpha-1C: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Hemagglutinin 1 shared papers
Voltage-dependent L-type calcium channel subunit beta-3 3 shared papers
Calcium-binding protein 1 2 shared papers
Voltage-dependent L-type calcium channel subunit alpha-1C 2 shared papers
Voltage-dependent L-type calcium channel subunit beta-2 1 shared papers
Voltage-dependent L-type calcium channel subunit beta-2 1 shared papers
Voltage-dependent calcium channel subunit alpha-2/delta-4 1 shared papers
Voltage-dependent L-type calcium channel subunit beta-3 1 shared papers
Voltage-dependent calcium channel subunit alpha-2/delta-3 1 shared papers
Voltage-dependent L-type calcium channel subunit alpha-1C 1 shared papers
SH3 and cysteine-rich domain-containing protein 2 1 shared papers
Voltage-dependent L-type calcium channel subunit alpha-1D 1 shared papers

Literature · 49 cited papers

Structural basis for human Cav1.2 inhibition by multiple drugs and the neurotoxin calciseptine. Cell · 2023
PMID 34522029 Genet. Med. · 2021
Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations. Genet. Med. · 2021
Characterization of the CACNA1C-R518C Missense Mutation in the Pathobiology of Long-QT Syndrome Using Human Induced Pluripotent Stem Cell Cardiomyocytes Shows Action Potential Prolongation and L-Type Calcium Channel Perturbation. Circ. Genom. Precis. Med. · 2019
Expanding clinical phenotype in CACNA1C related disorders: From neonatal onset severe epileptic encephalopathy to late-onset epilepsy. Am. J. Med. Genet. A · 2018
Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy. Mol. Genet. Genomic Med. · 2019
A pore-localizing CACNA1C-E1115K missense mutation, identified in a patient with idiopathic QT prolongation, bradycardia, and autism spectrum disorder, converts the L-type calcium channel into a hybrid nonselective monovalent cation channel. Heart Rhythm · 2019
A novel CACNA1C mutation identified in a patient with Timothy syndrome without syndactyly exerts both marked loss- and gain-of-function effects. HeartRhythm Case Rep. · 2018
Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells. Cell Host Microbe · 2018
Alternative Splicing at N Terminus and Domain I Modulates CaV1.2 Inactivation and Surface Expression. Biophys. J. · 2018
Structural insights into binding of STAC proteins to voltage-gated calcium channels. Proc. Natl. Acad. Sci. U.S.A. · 2017
Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2 and vasoconstriction during acute hyperglycemia and diabetes. Sci. Signal. · 2017
… and 37 more in the literature graph

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