Cav2.1

CACNA1A
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCACNA1A, APCA, BI, CACNL1A4, CAV2.1, EA2, FHM, HPCA, MHP, MHP1, SCA6, Cav2.1, calcium voltage-gated channel subunit alpha1 A, EIEE42, DEE42
External IDsOMIM: 601011; MGI: 109482; HomoloGene: 56383; GeneCards: CACNA1A; OMA:CACNA1A - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_023035
NM_000068
NM_001127221
NM_001127222
NM_001174080

NM_001252059
NM_001252060
NM_001252061
NM_007578

RefSeq (protein)

NP_000059
NP_001120693
NP_001120694
NP_001167551
NP_075461

NP_001238988
NP_001238989
NP_001238990
NP_031604

Location (UCSC)Chr 19: 13.21 – 13.63 MbChr 8: 85.07 – 85.37 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cav2.1, also called the P/Q voltage-dependent calcium channel, is a calcium channel found mainly in the brain.[5] Specifically, it is found on the presynaptic terminals of neurons in the brain and cerebellum.[5] Cav2.1 plays an important role in controlling the release of neurotransmitters between neurons.[5] It is composed of multiple subunits, including alpha-1, beta, alpha-2/delta, and gamma subunits.[6] The alpha-1 subunit is the pore-forming subunit, meaning that the calcium ions flow through it.[6] Different kinds of calcium channels have different isoforms (versions) of the alpha-1 subunit. Cav2.1 has the alpha-1A subunit,[6] which is encoded by the CACNA1A gene.[a][5] Mutations in CACNA1A have been associated with various neurologic disorders, including familial hemiplegic migraine, episodic ataxia type 2, and spinocerebellar ataxia type 6.[5]

Function

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"Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue."[6]

Clinical significance

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Mutations in the CACNA1A gene are associated with multiple neurologic disorders, many of which are episodic, such as familial hemiplegic migraine, movement disorders such as episodic ataxia, and epilepsy with multiple seizure types.[8]

"This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. However, in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-16 to 21-28 in the coding region is associated with spinocerebellar ataxia 6."[6]

Interactions

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Cav2.1 has been shown to interact with CACNB4.[9][10]

Notes

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  1. ^ "CACNA1A is an abbreviation of the gene's full name, CAlcium voltage-gated ChaNnel subunit AIpha 1A, which is a description of the protein coded for by the gene."[7]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000141837Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034656Ensembl, 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. ^ a b c d e Sutherland HG, Albury CL, Griffiths LR (21 June 2019). "Advances in genetics of migraine". The Journal of Headache and Pain. 20 (1): 72. doi:10.1186/s10194-019-1017-9. PMC 6734342. PMID 31226929.
  6. ^ a b c d e "CACNA1A". Gene. National Center for Biotechnology Information. 16 March 2021. Retrieved 28 March 2021.
  7. ^ "The Science of CACNA1A". CACNA1A Foundation. Retrieved 28 March 2021.
  8. ^ Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA (February 2020). "The expanding spectrum of movement disorders in genetic epilepsies". Developmental Medicine and Child Neurology. 62 (2): 178–191. doi:10.1111/dmcn.14407. PMID 31784983. S2CID 208498567.
  9. ^ Walker D, Bichet D, Campbell KP, De Waard M (January 1998). "A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit". The Journal of Biological Chemistry. 273 (4): 2361–7. doi:10.1074/jbc.273.4.2361. PMID 9442082.
  10. ^ Walker D, Bichet D, Geib S, Mori E, Cornet V, Snutch TP, et al. (April 1999). "A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation". The Journal of Biological Chemistry. 274 (18): 12383–90. doi:10.1074/jbc.274.18.12383. PMID 10212211.

Further reading

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Further reading

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