CACNA2D1 explained

Voltage-dependent calcium channel subunit alpha-2/delta-1 is a protein that in humans is encoded by the CACNA2D1 gene.^{[1] [2]}

This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed, but have not been thoroughly characterized.^[2]

Gabapentinoids

Alpha-2/delta proteins are believed to be the molecular target of the gabapentinoids gabapentin and pregabalin, which are used to treat epilepsy and neuropathic pain.^{[3] [4] [5]}

See also

• Voltage-dependent calcium channel

Further reading

• Williams ME, Feldman DH, McCue AF . Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype. . Neuron . 8 . 1 . 71–84 . 1992 . 1309651 . 10.1016/0896-6273(92)90109-Q . 39341712 . etal.
• Ellis SB, Williams ME, Ways NR . Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel. . Science . 241 . 4873 . 1661–4 . 1988 . 2458626 . 10.1126/science.2458626 . 1988Sci...241.1661E . etal.
• Iles DE, Lehmann-Horn F, Scherer SW . Localization of the gene encoding the alpha 2/delta-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families. . Hum. Mol. Genet. . 3 . 6 . 969–75 . 1994 . 7951247 . 10.1093/hmg/3.6.969 . etal.
• Brust PF, Simerson S, McCue AF . Human neuronal voltage-dependent calcium channels: studies on subunit structure and role in channel assembly. . Neuropharmacology . 32 . 11 . 1089–102 . 1994 . 8107964 . 10.1016/0028-3908(93)90004-M . 33257989 . etal.
• Toward a complete human genome sequence. . Genome Res. . 8 . 11 . 1097–108 . 1999 . 9847074 . 10.1101/gr.8.11.1097. Sanger Centre . The . Washington University Genome Sequencing Cente . The . free .
• Schleithoff L, Mehrke G, Reutlinger B, Lehmann-Horn F . Genomic structure and functional expression of a human alpha(2)/delta calcium channel subunit gene (CACNA2). . Genomics . 61 . 2 . 201–9 . 1999 . 10534405 . 10.1006/geno.1999.5941 .
• Bell DC, Butcher AJ, Berrow NS . Biophysical properties, pharmacology, and modulation of human, neuronal L-type (alpha(1D), Ca(V)1.3) voltage-dependent calcium currents. . J. Neurophysiol. . 85 . 2 . 816–27 . 2001 . 11160515 . 10.1152/jn.2001.85.2.816. 147295966 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Hillier LW, Fulton RS, Fulton LA . The DNA sequence of human chromosome 7. . Nature . 424 . 6945 . 157–64 . 2003 . 12853948 . 10.1038/nature01782 . 2003Natur.424..157H . etal. free .
• Stotz SC, Barr W, McRory JE . Several structural domains contribute to the regulation of N-type calcium channel inactivation by the beta 3 subunit. . J. Biol. Chem. . 279 . 5 . 3793–800 . 2004 . 14602720 . 10.1074/jbc.M308991200 . etal. free .
• Liu T, Qian WJ, Gritsenko MA . Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. . J. Proteome Res. . 4 . 6 . 2070–80 . 2006 . 16335952 . 10.1021/pr0502065 . 1850943 . etal.
• Antzelevitch C, Pollevick GD, Cordeiro JM . Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. . Circulation . 115 . 4 . 442–9 . 2007 . 17224476 . 10.1161/CIRCULATIONAHA.106.668392 . 1952683 . etal.
• Chaudhuri D, Issa JB, Yue DT . Elementary mechanisms producing facilitation of Cav2.1 (P/Q-type) channels. . J. Gen. Physiol. . 129 . 5 . 385–401 . 2007 . 17438119 . 10.1085/jgp.200709749 . 2154375 .

Notes and References

1. Powers PA, Scherer SW, Tsui LC, Gregg RG, Hogan K . Localization of the gene encoding the alpha 2/delta subunit (CACNL2A) of the human skeletal muscle voltage-dependent Ca2+ channel to chromosome 7q21-q22 by somatic cell hybrid analysis . Genomics . 19 . 1 . 192–3 . Jun 1994 . 8188232 . 10.1006/geno.1994.1044 .
2. Web site: Entrez Gene: CACNA2D1 calcium channel, voltage-dependent, alpha 2/delta subunit 1.
3. Rogawski MA, Bazil CW . New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels . Curr Neurol Neurosci Rep . July 2008 . 8 . 4 . 345–52 . 18590620 . 10.1007/s11910-008-0053-7 . 2587091.
4. Patel. Ryan. Dickenson. Anthony H.. 2016-04-01. Mechanisms of the gabapentinoids andα2δ-1 calcium channel subunit in neuropathic pain. Pharmacology Research & Perspectives. en. 4. 2. e00205. 10.1002/prp2.205. 27069626. 2052-1707. 4804325.
5. Patel. Ryan. Bauer. Claudia S.. Nieto-Rostro. Manuela. Margas. Wojciech. Ferron. Laurent. Chaggar. Kanchan. Crews. Kasumi. Ramirez. Juan D.. Bennett. David L. H.. 2013-10-16. α2δ-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage. Journal of Neuroscience. 33. 42. 16412–16426. 10.1523/jneurosci.1026-13.2013. 24133248. 3797367.