CACNA2D1

CACNA2D1
Identifiers
Aliases	CACNA2D1, CACNA2, CACNL2A, CCHL2A, LINC01112, lncRNA-N3, calcium voltage-gated channel auxiliary subunit alpha2delta 1
External IDs	OMIM: 114204; MGI: 88295; HomoloGene: 579; GeneCards: CACNA2D1; OMA:CACNA2D1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) Band 7q21.11 Start 81,946,444 bp End 82,443,777 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5 A2- A3|5 6.56 cM Start 16,139,689 bp End 16,579,509 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in biceps brachii Skeletal muscle tissue of biceps brachii Skeletal muscle tissue of rectus abdominis body of tongue endothelial cell postcentral gyrus Brodmann area 23 entorhinal cortex right ventricle middle temporal gyrus Top expressed in triceps brachii muscle temporal muscle digastric muscle ankle sternocleidomastoid muscle ventromedial nucleus muscle of thigh vastus lateralis muscle dorsomedial hypothalamic nucleus body of femur More reference expression data BioGPS More reference expression data
Gene ontology Molecular function voltage-gated calcium channel activity metal ion binding voltage-gated ion channel activity calcium channel activity voltage-gated calcium channel activity involved in cardiac muscle cell action potential voltage-gated calcium channel activity involved in bundle of His cell action potential Cellular component voltage-gated calcium channel complex L-type voltage-gated calcium channel complex integral component of membrane T-tubule plasma membrane extracellular exosome membrane sarcoplasmic reticulum Biological process regulation of ion transmembrane transport regulation of calcium ion transport cardiac conduction ion transport calcium ion transmembrane transport calcium ion transport transport cardiac muscle cell action potential involved in contraction calcium ion transport into cytosol positive regulation of high voltage-gated calcium channel activity regulation of heart rate by cardiac conduction calcium ion transmembrane transport via high voltage-gated calcium channel regulation of ventricular cardiac muscle cell membrane repolarization regulation of membrane repolarization during action potential membrane depolarization during bundle of His cell action potential calcium ion import across plasma membrane regulation of calcium ion transmembrane transport via high voltage-gated calcium channel cellular response to amyloid-beta Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 781 12293 Ensembl ENSG00000153956 ENSMUSG00000040118 UniProt P54289 O08532 RefSeq (mRNA) NM_000722 NM_001302890 NM_001366867 NM_001110843 NM_001110844 NM_001110845 NM_001110846 NM_009784 RefSeq (protein) NP_000713 NP_001289819 NP_001353796 NP_001104313 NP_001104314 NP_001104315 NP_001104316 NP_033914 Location (UCSC) Chr 7: 81.95 – 82.44 Mb Chr 5: 16.14 – 16.58 Mb PubMed search
Wikidata
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Voltage-dependent calcium channel subunit alpha-2/delta-1 is a protein that in humans is encoded by the CACNA2D1 gene.

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 depolarization 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.

In mammals, alpha-2/delta proteins exist in four subtypes coded by four separate but closely related genes, CACNA2D1, CACNA2D2, CACNA2D3 and CACNA2D4.

Recently, alpha-2/delta1 proteins, in addition to calcium channels, have been found to interact directly with N-methyl-D-aspartate type glutamate receptors (NMDAR), AMPA type glutamate receptors (AMPAR) and the extracellular adhesion protein, thrombospondin.

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. Only alpha-2/delta subtypes 1 and 2 (but not 3 and 4) are substrates for gabapentinoid drug binding.

See also

• Voltage-dependent calcium channel
• Gabapentinoid drugs

Further reading

• Williams ME, Feldman DH, McCue AF, et al. (1992). "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. doi:10.1016/0896-6273(92)90109-Q. PMID 1309651. S2CID 39341712.
• Ellis SB, Williams ME, Ways NR, et al. (1988). "Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel". Science. 241 (4873): 1661–4. Bibcode:1988Sci...241.1661E. doi:10.1126/science.2458626. PMID 2458626.
• Iles DE, Lehmann-Horn F, Scherer SW, et al. (1994). "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. doi:10.1093/hmg/3.6.969. PMID 7951247.
• Brust PF, Simerson S, McCue AF, et al. (1994). "Human neuronal voltage-dependent calcium channels: studies on subunit structure and role in channel assembly". Neuropharmacology. 32 (11): 1089–102. doi:10.1016/0028-3908(93)90004-M. PMID 8107964. S2CID 33257989.
• Sanger Centre, The; Washington University Genome Sequencing Cente, The (1999). "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. doi:10.1101/gr.8.11.1097. PMID 9847074.
• Schleithoff L, Mehrke G, Reutlinger B, Lehmann-Horn F (1999). "Genomic structure and functional expression of a human alpha(2)/delta calcium channel subunit gene (CACNA2)". Genomics. 61 (2): 201–9. doi:10.1006/geno.1999.5941. PMID 10534405.
• Bell DC, Butcher AJ, Berrow NS, et al. (2001). "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. doi:10.1152/jn.2001.85.2.816. PMID 11160515. S2CID 147295966.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Hillier LW, Fulton RS, Fulton LA, et al. (2003). "The DNA sequence of human chromosome 7". Nature. 424 (6945): 157–64. Bibcode:2003Natur.424..157H. doi:10.1038/nature01782. PMID 12853948.
• Stotz SC, Barr W, McRory JE, et al. (2004). "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. doi:10.1074/jbc.M308991200. PMID 14602720.
• Liu T, Qian WJ, Gritsenko MA, et al. (2006). "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". J. Proteome Res. 4 (6): 2070–80. doi:10.1021/pr0502065. PMC 1850943. PMID 16335952.
• Antzelevitch C, Pollevick GD, Cordeiro JM, et al. (2007). "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. doi:10.1161/CIRCULATIONAHA.106.668392. PMC 1952683. PMID 17224476.
• Chaudhuri D, Issa JB, Yue DT (2007). "Elementary mechanisms producing facilitation of Cav2.1 (P/Q-type) channels". J. Gen. Physiol. 129 (5): 385–401. doi:10.1085/jgp.200709749. PMC 2154375. PMID 17438119.

External links

• CACNA2D1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human CACNA2D1 genome location and CACNA2D1 gene details page in the UCSC Genome Browser.

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