Cav1.2

Calcium channel, voltage-dependent, L type, alpha 1C subunit

PDB rendering based on 2be6.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsCACNA1C ; CACH2; CACN2; CACNL1A1; CCHL1A1; CaV1.2; LQT8; TS
External IDsOMIM: 114205 MGI: 103013 HomoloGene: 55484 IUPHAR: 529 ChEMBL: 1940 GeneCards: CACNA1C Gene
Orthologs
SpeciesHumanMouse
Entrez77512288
EnsemblENSG00000151067ENSMUSG00000051331
UniProtQ13936Q01815
RefSeq (mRNA)NM_000719NM_001159533
RefSeq (protein)NP_000710NP_001153005
Location (UCSC)Chr 12:
2.08 – 2.8 Mb		Chr 6:
118.59 – 118.78 Mb
PubMed search

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

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

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

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

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Nicotine Activity on Chromaffin Cells edit

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

See also

References

  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 summary – Schizophrenia 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. 18: 526–527. doi:10.1038/mp.2012.61. PMID 22614292.

Further reading

  • Kempton MJ, Ruberto G, Vassos E, Tatarelli R, Girardi P, Collier D, Frangou S (December 2009). "Effects of the CACNA1C risk allele for bipolar disorder on cerebral gray matter volume in healthy individuals". Am J Psychiatry 166 (12): 1413–4. doi:10.1176/appi.ajp.2009.09050680. PMID 19952088.
  • Soldatov NM (1992). "Molecular diversity of L-type Ca2+ channel transcripts in human fibroblasts". Proc. Natl. Acad. Sci. U.S.A. 89 (10): 4628–32. doi:10.1073/pnas.89.10.4628. PMC 49136. PMID 1316612.
  • Powers PA, Gregg RG, Hogan K (1992). "Linkage mapping of the human gene for the alpha 1 subunit of the cardiac DHP-sensitive Ca2+ channel (CACNL1A1) to chromosome 12p13.2-pter using a dinucleotide repeat". Genomics 14 (1): 206–7. doi:10.1016/S0888-7543(05)80312-X. PMID 1330882.
  • Sun W, McPherson JD, Hoang DQ et al. (1993). "Mapping of a human brain voltage-gated calcium channel to human chromosome 12p13-pter". Genomics 14 (4): 1092–4. doi:10.1016/S0888-7543(05)80135-1. PMID 1335957.
  • Powers PA, Gregg RG, Lalley PA et al. (1991). "Assignment of the human gene for the alpha 1 subunit of the cardiac DHP-sensitive Ca2+ channel (CCHL1A1) to chromosome 12p12-pter". Genomics 10 (3): 835–9. doi:10.1016/0888-7543(91)90471-P. PMID 1653763.
  • Perez-Reyes E, Wei XY, Castellano A, Birnbaumer L (1990). "Molecular diversity of L-type calcium channels. Evidence for alternative splicing of the transcripts of three non-allelic genes". J. Biol. Chem. 265 (33): 20430–6. PMID 2173707.
  • Soldatov NM, Bouron A, Reuter H (1995). "Different voltage-dependent inhibition by dihydropyridines of human Ca2+ channel splice variants". J. Biol. Chem. 270 (18): 10540–3. doi:10.1074/jbc.270.18.10540. PMID 7737988.
  • Soldatov NM (1994). "Genomic structure of human L-type Ca2+ channel". Genomics 22 (1): 77–87. doi:10.1006/geno.1994.1347. PMID 7959794.
  • Tang S, Mikala G, Bahinski A et al. (1993). "Molecular localization of ion selectivity sites within the pore of a human L-type cardiac calcium channel". J. Biol. Chem. 268 (18): 13026–9. PMID 8099908.
  • Schultz D, Mikala G, Yatani A et al. (1993). "Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart". Proc. Natl. Acad. Sci. U.S.A. 90 (13): 6228–32. doi:10.1073/pnas.90.13.6228. PMC 46901. PMID 8392192.
  • Perets T, Blumenstein Y, Shistik E et al. (1996). "A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel alpha 1C subunit". FEBS Lett. 384 (2): 189–92. doi:10.1016/0014-5793(96)00303-1. PMID 8612821.
  • Andersson B, Wentland MA, Ricafrente JY et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
  • Soldatov NM, Zühlke RD, Bouron A, Reuter H (1997). "Molecular structures involved in L-type calcium channel inactivation. Role of the carboxyl-terminal region encoded by exons 40-42 in alpha1C subunit in the kinetics and Ca2+ dependence of inactivation". J. Biol. Chem. 272 (6): 3560–6. doi:10.1074/jbc.272.6.3560. PMID 9013606.
  • Klöckner U, Mikala G, Eisfeld J et al. (1997). "Properties of three COOH-terminal splice variants of a human cardiac L-type Ca2+-channel alpha1-subunit". Am. J. Physiol. 272 (3 Pt 2): H1372–81. PMID 9087614.
  • Yu W, Andersson B, Worley KC et al. (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
  • Gao T, Yatani A, Dell'Acqua ML et al. (1997). "cAMP-dependent regulation of cardiac L-type Ca2+ channels requires membrane targeting of PKA and phosphorylation of channel subunits". Neuron 19 (1): 185–96. doi:10.1016/S0896-6273(00)80358-X. PMID 9247274.
  • Zühlke RD, Bouron A, Soldatov NM, Reuter H (1998). "Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human alpha1C subunit gene". FEBS Lett. 427 (2): 220–4. doi:10.1016/S0014-5793(98)00425-6. PMID 9607315.
  • Meyers MB, Puri TS, Chien AJ et al. (1998). "Sorcin associates with the pore-forming subunit of voltage-dependent L-type Ca2+ channels". J. Biol. Chem. 273 (30): 18930–5. doi:10.1074/jbc.273.30.18930. PMID 9668070.
  • Liu WS, Soldatov NM, Gustavsson I, Chowdhary BP (1999). "Fiber-FISH analysis of the 3'-terminal region of the human L-type Ca2+ channel alpha 1C subunit gene". Hereditas 129 (2): 169–75. doi:10.1111/j.1601-5223.1998.00169.x. PMID 10022083.

External links

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