Cav1.2

CACNA1C
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1T0J, 2BE6, 2F3Z, 2LQC, 3G43, 3OXQ
Identifiers
Aliases	CACNA1C, CACH2, CACN2, CACNL1A1, CCHL1A1, CaV1.2, LQT8, TS, calcium voltage-gated channel subunit alpha1 C, TS. LQT8
External IDs	OMIM: 114205 MGI: 103013 HomoloGene: 55484 GeneCards: CACNA1C
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12p13.33 Start 1,970,772 bp[1] End 2,697,950 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 F1|6 55.86 cM Start 118,564,201 bp[2] End 119,173,851 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right coronary artery left ventricle myometrium smooth muscle tissue popliteal artery left coronary artery ascending aorta sural nerve urinary bladder fundus Top expressed in interventricular septum right ventricle medial dorsal nucleus lateral geniculate nucleus atrium medial geniculate nucleus olfactory tubercle piriform cortex adrenal gland aortic valve More reference expression data BioGPS n/a
Gene ontology Molecular function calcium channel activity metal ion binding voltage-gated ion channel activity ion channel activity protein binding alpha-actinin binding voltage-gated calcium channel activity voltage-gated calcium channel activity involved in cardiac muscle cell action potential high voltage-gated calcium channel activity voltage-gated calcium channel activity involved in AV node cell action potential calmodulin binding Cellular component cytoplasm voltage-gated calcium channel complex integral component of membrane membrane postsynaptic density plasma membrane Z disc L-type voltage-gated calcium channel complex integral component of plasma membrane cell junction dendrite sarcolemma cell projection perikaryon synapse postsynaptic membrane T-tubule Biological process calcium ion transport into cytosol regulation of insulin secretion regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion positive regulation of cytosolic calcium ion concentration cell communication by electrical coupling involved in cardiac conduction regulation of ion transmembrane transport ion transport calcium-mediated signaling using extracellular calcium source transmembrane transport calcium ion transport regulation of ventricular cardiac muscle cell action potential embryonic forelimb morphogenesis immune system development regulation of heart rate by cardiac conduction membrane depolarization during cardiac muscle cell action potential calcium ion transmembrane transport via high voltage-gated calcium channel membrane depolarization during AV node cell action potential heart development membrane depolarization during atrial cardiac muscle cell action potential cardiac muscle cell action potential involved in contraction calcium ion transmembrane transport camera-type eye development cardiac conduction calcium ion import positive regulation of adenylate cyclase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 775 12288 Ensembl ENSG00000151067 ENSG00000285479 ENSMUSG00000051331 UniProt Q13936 Q01815 RefSeq (mRNA) NM_000719 NM_001129827 NM_001129829 NM_001129830 NM_001129831 NM_001129832 NM_001129833 NM_001129834 NM_001129835 NM_001129836 NM_001129837 NM_001129838 NM_001129839 NM_001129840 NM_001129841 NM_001129842 NM_001129843 NM_001129844 NM_001129846 NM_001167623 NM_001167624 NM_001167625 NM_199460 NM_001159533 NM_001159534 NM_001159535 NM_001255997 NM_001255998 NM_001255999 NM_001256000 NM_001256001 NM_001256002 NM_009781 NM_001290335 RefSeq (protein) NP_000710 NP_001123299 NP_001123301 NP_001123302 NP_001123303 NP_001123304 NP_001123305 NP_001123306 NP_001123307 NP_001123308 NP_001123309 NP_001123310 NP_001123311 NP_001123312 NP_001123313 NP_001123314 NP_001123315 NP_001123316 NP_001123318 NP_001161095 NP_001161096 NP_001161097 NP_955630 NP_001153005 NP_001153006 NP_001153007 NP_001242926 NP_001242927 NP_001242928 NP_001242929 NP_001242930 NP_001242931 NP_001277264 NP_033911 Location (UCSC) Chr 12: 1.97 – 2.7 Mb Chr 6: 118.56 – 119.17 Mb PubMed search [3] [4]
Wikidata
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Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Ca_v1.2) is a protein that in humans is encoded by the CACNA1C gene.^[5] Ca_v1.2 is a subunit of L-type voltage-dependent calcium channel.^[6]

Structure and function

This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions (Ca²⁺) into the cell upon membrane polarization (see membrane potential and calcium in biology).^[7]

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 and beta subunits in a 1:1:1 ratio. The S3-S4 linkers of Cav1.2 determine the gating phenotype and modulated gating kinetics of the channel.^[8] Cav1.2 is widely expressed in the smooth muscle, pancreatic cells, fibroblasts, and neurons.^[9][10] However, it is particularly important and well known for its expression in the heart where it mediates L-type currents, which causes calcium-induced calcium release from the ER Stores via ryanodine receptors. It depolarizes at -30mV and helps define the shape of the action potential in cardiac and smooth muscle.^[8] The protein encoded by this gene binds to and is inhibited by dihydropyridine.^[11] In the arteries of the brain, high levels of calcium in mitochondria elevates activity of nuclear factor kappa B NF-κB and transcription of CACNA1c and functional Cav1.2 expression increases.^[12] Cav1.2 also regulates levels of osteoprotegerin.^[13]

Ca_V1.2 is inhibited by the action of STIM1.^[14]

Regulation

The activity of CaV1.2 channels is tightly regulated by the Ca²⁺ signals they produce. An increase in intracellular Ca²⁺ concentration implicated in Cav1.2 facilitation, a form of positive feedback called Ca²⁺-dependent facilitation, that amplifies Ca²⁺ influx. In addition, increasing influx intracellular Ca²⁺ concentration has implicated to exert the opposite effect Ca2+ dependent inactivation.^[15] These activation and inactivation mechanisms both involve Ca²⁺ binding to calmodulin (CaM) in the IQ domain in the C-terminal tail of these channels.^[16] Cav1.2 channels are arranged in cluster of eight, on average, in the cell membrane. When calcium ions bind to calmodulin, which in turn binds to a Cav1.2 channel, it allows the Cav1.2 channels within a cluster to interact with each other.^[17] This results in channels working cooperatively when they open at the same time to allow more calcium ions to enter and then close together to allow the cell to relax.^[17]

Clinical significance

Mutation in the CACNA1C gene, the single-nucleotide polymorphism located in the third intron of the Cav1.2 gene,^[18] are associated with a variant of Long QT syndrome called Timothy's syndrome^[19] and more broadly with other CACNA1C-related disorders,^[19] and also with Brugada syndrome.^[20] Large-scale genetic analyses have shown the possibility that CACNA1C is associated with bipolar disorder^[21] and subsequently also with schizophrenia.^[22][23][24] Also, a CACNA1C risk allele has been associated to a disruption in brain connectivity in patients with bipolar disorder, while not or only to a minor degree, in their unaffected relatives or healthy controls.^[25].In a first study in Indian population, the Schizophrenia associated Genome-wide association study (GWAS) SNP was found not to be associated with the disease. Furthermore, the main effect of rs1006737 was found to be associated with spatial ability_efficiency scores. Subjects with genotypes carrying the risk allele of rs1006737 (G/A and A/A) were found to have higher spatial ability_efficiency scores as compared to those with the G/G genotype. While in healthy controls those with G/A and A/A genotypes were found to have higher spatial memory_{processing speed} scores than those with G/G genotypes, the former had lower scores than the latter in schizophrenia subjects. In the same study the genotypes with the risk allele of rs1006737 namely A/A was associated with a significantly lower Align rank transformed Abnormal and involuntary movement scale(AIMS) scores of Tardive dyskinesia(TD).^[26]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective Wikipedia articles. ^{[§ 1]}

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|alt=Nicotine Activity on Chromaffin Cells edit]]

Nicotine Activity on Chromaffin Cells edit

1. ^ The interactive pathway map can be edited at WikiPathways: "NicotineActivityonChromaffinCells_WP1603".

See also

• Calcium channel
• Calcium channel associated transcriptional regulator

References

Further reading

External links

• GeneReviews/NIH/NCBI/UW entry on Brugada syndrome
• CACNA1C+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• GeneReviews/NIH/NCBI/UW entry on Timothy Syndrome

This article incorporates text from the United States National Library of Medicine, which is in the public domain.