Biology:Cav2.1

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Ca_v2.1, also called the P/Q voltage-dependent calcium channel, is a calcium channel found mainly in the brain. Specifically, it is found on the presynaptic terminals of neurons in the brain and cerebellum. Ca_v2.1 plays an important role in controlling the release of neurotransmitters between neurons. It is composed of multiple subunits, including alpha-1, beta, alpha-2/delta, and gamma subunits. The alpha-1 subunit is the pore-forming subunit, meaning that the calcium ions flow through it. Different kinds of calcium channels have different isoforms (versions) of the alpha-1 subunit. Ca_v2.1 has the alpha-1A subunit, which is encoded by the CACNA1A gene. Mutations in CACNA1A have been associated with various neurologic disorders, including familial hemiplegic migraine, episodic ataxia type 2, and spinocerebellar ataxia type 6.

Function

"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."

Clinical significance

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.

"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."

Interactions

Cav2.1 has been shown to interact with CACNB4.

Further reading

• "Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine". Archives of Neurology 59 (6): 1016–8. June 2002. doi:10.1001/archneur.59.6.1016. PMID 12056940. 
• "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacological Reviews 57 (4): 411–25. December 2005. doi:10.1124/pr.57.4.5. PMID 16382099. 
• "Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel". The Journal of Biological Chemistry 267 (3): 1792–7. January 1992. doi:10.1016/S0021-9258(18)46015-2. PMID 1370480. 
• "Expression and antibody inhibition of P-type calcium channels in human small-cell lung carcinoma cells". The Journal of Neuroscience 15 (1 Pt 1): 274–83. January 1995. doi:10.1523/JNEUROSCI.15-01-00274.1995. PMID 7823133. 
• "A gene for familial hemiplegic migraine maps to chromosome 19". Nature Genetics 5 (1): 40–5. September 1993. doi:10.1038/ng0993-40. PMID 8220421. 
• "Characterization of cDNA clones containing CCA trinucleotide repeats derived from human brain". Somatic Cell and Molecular Genetics 21 (4): 279–84. July 1995. doi:10.1007/BF02255782. PMID 8525433. 
• "Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25". Proceedings of the National Academy of Sciences of the United States of America 93 (14): 7363–8. July 1996. doi:10.1073/pnas.93.14.7363. PMID 8692999. Bibcode: 1996PNAS...93.7363R. 
• "Chromosomal localization of the human genes for alpha 1A, alpha 1B, and alpha 1E voltage-dependent Ca2+ channel subunits". Genomics 30 (3): 605–9. December 1995. doi:10.1006/geno.1995.1284. PMID 8825650. 
• "Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4". Cell 87 (3): 543–52. November 1996. doi:10.1016/S0092-8674(00)81373-2. PMID 8898206. 
• "Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel". Nature Genetics 15 (1): 62–9. January 1997. doi:10.1038/ng0197-62. PMID 8988170. 
• "Direct binding of G-protein betagamma complex to voltage-dependent calcium channels". Nature 385 (6615): 446–50. January 1997. doi:10.1038/385446a0. PMID 9009193. Bibcode: 1997Natur.385..446W. 
• "Direct interaction of gbetagamma with a C-terminal gbetagamma-binding domain of the Ca2+ channel alpha1 subunit is responsible for channel inhibition by G protein-coupled receptors". Proceedings of the National Academy of Sciences of the United States of America 94 (16): 8866–71. August 1997. doi:10.1073/pnas.94.16.8866. PMID 9238069. 
• "SCA6 is caused by moderate CAG expansion in the alpha1A-voltage-dependent calcium channel gene". Human Molecular Genetics 6 (8): 1289–93. August 1997. doi:10.1093/hmg/6.8.1289. PMID 9259275. 
• "Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p". Human Molecular Genetics 6 (11): 1973–8. October 1997. doi:10.1093/hmg/6.11.1973. PMID 9302278. 
• "Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel". The EMBO Journal 16 (15): 4591–6. August 1997. doi:10.1093/emboj/16.15.4591. PMID 9303303. 
• "Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1". American Journal of Human Genetics 61 (2): 336–46. August 1997. doi:10.1086/514867. PMID 9311738. 
• "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. January 1998. doi:10.1074/jbc.273.4.2361. PMID 9442082. 
• "De novo mutation in CACNA1A caused acetazolamide-responsive episodic ataxia". American Journal of Medical Genetics 77 (4): 298–301. May 1998. doi:10.1002/(SICI)1096-8628(19980526)77:4<298::AID-AJMG9>3.0.CO;2-J. PMID 9600739. 
• "Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels". Biophysical Journal 76 (3): 1384–400. March 1999. doi:10.1016/S0006-3495(99)77300-5. PMID 10049321. Bibcode: 1999BpJ....76.1384H. 
• "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. April 1999. doi:10.1074/jbc.274.18.12383. PMID 10212211. 

• Nikonishyna, Yuliia V. (2022). "Novel CACNA1A Variant p.Cys256Phe Disrupts Disulfide Bonds and Causes Spinocerebellar Ataxia". Movement Disorders (Movement disorders: official journal of the Movement Disorder Society) 37 (2): 401–404. doi:10.1002/mds.28835. PMID 34647648. 

Further reading

• Jen, Joanna C (May 2015) [1993]. "Familial Hemiplegic Migraine". GeneReviews. Seattle WA: University of Washington, Seattle. NBK1388. https://www.ncbi.nlm.nih.gov/books/NBK1388/. 
• Spacey, Sian (December 2011). "Episodic Ataxia Type 2 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY". Episodic Ataxia Type 2. University of Washington, Seattle. NBK1501. https://www.ncbi.nlm.nih.gov/books/NBK1501/.  In GeneReviews
• Gomez, Christopher M (July 2013). Spinocerebellar Ataxia Type 6. University of Washington, Seattle. NBK1140. https://www.ncbi.nlm.nih.gov/books/NBK1140/.  In GeneReviews

• CACNA1A+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)