CACNA2D1

CACNA2D1
Identifiers
AliasesCACNA2D1, CACNA2, CACNL2A, CCHL2A, LINC01112, lncRNA-N3, calcium voltage-gated channel auxiliary subunit alpha2delta 1
External IDsOMIM: 114204; MGI: 88295; HomoloGene: 579; GeneCards: CACNA2D1; OMA:CACNA2D1 - orthologs
Orthologs
SpeciesHumanMouse
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 MbChr 5: 16.14 – 16.58 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Voltage-dependent calcium channel subunit alpha-2/delta-1 is a protein that in humans is encoded by the CACNA2D1 gene.[5][6]

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.[6]

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.[7]

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.[8][9][10] Only alpha-2/delta subtypes 1 and 2 (but not 3 and 4) are substrates for gabapentinoid drug binding.

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000153956 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040118 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Powers PA, Scherer SW, Tsui LC, Gregg RG, Hogan K (Jun 1994). "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. doi:10.1006/geno.1994.1044. PMID 8188232.
  6. ^ a b "Entrez Gene: CACNA2D1 calcium channel, voltage-dependent, alpha 2/delta subunit 1".
  7. ^ Varadi, Gyula (2024). "Mechanism of Analgesia by Gabapentinoid Drugs: Involvement of Modulation of Synaptogenesis and Trafficking of Glutamate-Gated Ion Channels". Journal of Pharmacology and Experimental Therapeutics. 388 (1): 121–133. doi:10.1124/jpet.123.001669. ISSN 0022-3565. PMID 37918854.
  8. ^ Rogawski MA, Bazil CW (July 2008). "New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels". Curr Neurol Neurosci Rep. 8 (4): 345–52. doi:10.1007/s11910-008-0053-7. PMC 2587091. PMID 18590620.
  9. ^ Patel, Ryan; Dickenson, Anthony H. (2016-04-01). "Mechanisms of the gabapentinoids andα2δ-1 calcium channel subunit in neuropathic pain". Pharmacology Research & Perspectives. 4 (2): e00205. doi:10.1002/prp2.205. ISSN 2052-1707. PMC 4804325. PMID 27069626.
  10. ^ 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. doi:10.1523/jneurosci.1026-13.2013. PMC 3797367. PMID 24133248.

Further reading

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


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