Cav1.2

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Calcium channel, voltage-dependent, L type, alpha 1C subunit
Protein CACNA1C PDB 2be6.png
PDB rendering based on 2be6.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CACNA1C ; CACH2; CACN2; CACNL1A1; CCHL1A1; CaV1.2; LQT8; TS
External IDs OMIM114205 MGI103013 HomoloGene55484 IUPHAR: Cav1.2 ChEMBL: 1940 GeneCards: CACNA1C Gene
Orthologs
Species Human Mouse
Entrez 775 12288
Ensembl ENSG00000151067 ENSMUSG00000051331
UniProt Q13936 Q01815
RefSeq (mRNA) NM_000719 NM_001159533
RefSeq (protein) NP_000710 NP_001153005
Location (UCSC) Chr 12:
2.08 – 2.8 Mb
Chr 6:
118.59 – 118.78 Mb
PubMed search [1] [2]

Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Cav1.2) is a protein that in humans is encoded by the CACNA1C gene.[1] Cav1.2 is a subunit of L-type voltage-dependent calcium channel.[2]

Structure and function[edit]

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 and beta subunits in a 1:1:1 ratio. Cav1.2 is widely expressed, 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. The protein encoded by this gene binds to and is inhibited by dihydropyridine.[3] 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.[4] Cav1.2 also regulates levels of osteoprotegerin.[5]

CaV1.2 is inhibited by the action of STIM1.[6]

Clinical significance[edit]

Mutation in the CACNA1C gene are associated with a variant of Long QT syndrome called Timothy's syndrome[7] and also with Brugada syndrome.[8] A large-scale genetic analysis conducted in 2008 shows the possibility that CACNA1C is associated with bipolar disorder [9] and subsequently also with schizophrenia.[10][11] Also, CACNA1C A 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.[12]

Interactive pathway map[edit]

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

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

See also[edit]

References[edit]

  1. ^ Lacerda AE, Kim HS, Ruth P, Perez-Reyes E, Flockerzi V, Hofmann F, Birnbaumer L, Brown AM (August 1991). "Normalization of current kinetics by interaction between the alpha 1 and beta subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel". Nature 352 (6335): 527–30. doi:10.1038/352527a0. PMID 1650913. 
  2. ^ Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (December 2005). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacol. Rev. 57 (4): 411–25. doi:10.1124/pr.57.4.5. PMID 16382099. 
  3. ^ "Entrez Gene: , voltage-dependent, L type, alpha 1C subunit". 
  4. ^ Narayanan D, Xi Q, Pfeffer LM, Jaggar JH (September 2010). "Mitochondria control functional CaV1.2 expression in smooth muscle cells of cerebral arteries". Circ. Res. 107 (5): 631–41. doi:10.1161/CIRCRESAHA.110.224345. PMC 3050675. PMID 20616314. 
  5. ^ Bergh JJ, Xu Y, Farach-Carson MC (January 2004). "Osteoprotegerin expression and secretion are regulated by calcium influx through the L-type voltage-sensitive calcium channel". Endocrinology 145 (1): 426–36. doi:10.1210/en.2003-0319. PMID 14525906. 
  6. ^ Calahan MD (October 2010). "Cell biology. How to STIMulate calcium channels.". Science 330 (1): 43–4. doi:10.1126/science.1196348. PMID 20929798. 
  7. ^ Pagon RA, Bird TC, Dolan CR, Stephens K, Splawski I, Timothy KW, Priori SG, Napolitano C, Bloise R (1993). Timothy Syndrome. PMID 20301577. 
  8. ^ Hedley PL, Jørgensen P, Schlamowitz S, Moolman-Smook J, Kanters JK, Corfield VA, Christiansen M (September 2009). "The genetic basis of Brugada syndrome: a mutation update". Hum. Mutat. 30 (9): 1256–66. doi:10.1002/humu.21066. PMID 19606473. 
  9. ^ Ferreira MA, O'Donovan MC, Meng YA, et al. (September 2008). "Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder". Nat. Genet. 40 (9): 1056–8. doi:10.1038/ng.209. PMC 2703780. PMID 18711365. Lay summarySchizophrenia Research Forum. 
  10. ^ Green EK, Grozeva D, Jones I, Jones L, Kirov G, Caesar S, Gordon-Smith K, Fraser C, Forty L, Russell E, Hamshere ML, Moskvina V, Nikolov I, Farmer A, McGuffin P, Holmans PA, Owen MJ, O'Donovan MC, Craddock N (October 2010). "The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia". Mol. Psychiatry 15 (10): 1016–22. doi:10.1038/mp.2009.49. PMC 3011210. PMID 19621016. 
  11. ^ Curtis D, Vine AE, McQuillin A, Bass NJ, Pereira A, Kandaswamy R, Lawrence J, Anjorin A, Choudhury K, Datta SR, Puri V, Krasucki R, Pimm J, Thirumalai S, Quested D, Gurling HM (February 2011). "Case-case genome-wide association analysis shows markers differentially associated with schizophrenia and bipolar disorder and implicates calcium channel genes". Psychiatr. Genet. 21 (1): 1–4. doi:10.1097/YPG.0b013e3283413382. PMC 3024533. PMID 21057379. 
  12. ^ Radua J, Surguladze SA, Marshall N, Walshe M, Bramon E, Collier DA, Prata DP, Murray RM, McDonald C (2012). "The impact of CACNA1C allelic variation on effective connectivity during emotional processing in bipolar disorder". Mol. Psychiatry. doi:10.1038/mp.2012.61. PMID 22614292. 

Further reading[edit]

External links[edit]

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