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{{Short description|Protein found in humans}}
{{DISPLAYTITLE:Ca<sub>v</sub>2.1}}
{{DISPLAYTITLE:Ca<sub>v</sub>2.1}}
{{Infobox_gene}}'''Ca<sub>v</sub>2.1''', also called the [[P-type calcium channel|P]]/[[Q-type calcium channel|Q]] [[voltage-dependent calcium channel]], is a calcium channel found mainly in the [[brain]].<ref name="Migraine Genetics">{{cite journal | vauthors = Sutherland HG, Albury CL, Griffiths LR | title = Advances in genetics of migraine | journal = The Journal of Headache and Pain | volume = 20 | issue = 1 | date = 21 June 2019 | page = 72 | pmid = 31226929 | doi = 10.1186/s10194-019-1017-9| pmc = 6734342 | doi-access = free }}</ref> Specifically, it is found on the presynaptic terminals of [[neuron]]s in the brain and [[cerebellum]].<ref name="Migraine Genetics"/> Ca<sub>v</sub>2.1 plays an important role in controlling the release of [[neurotransmitter]]s between neurons.<ref name="Migraine Genetics"/> It is composed of multiple subunits, including alpha-1, beta, alpha-2/delta, and gamma subunits.<ref name="NCBI"/> The alpha-1 subunit is the pore-forming subunit, meaning that the calcium ions flow through it.<ref name="NCBI"/> Different kinds of calcium channels have different [[isoform]]s (versions) of the alpha-1 subunit. Ca<sub>v</sub>2.1 has the alpha-1A subunit,<ref name="NCBI"/> which is encoded by the ''CACNA1A'' gene.{{efn|"''CACNA1A'' is an abbreviation of the gene's full name, '''CA'''lcium voltage-gated '''C'''ha'''N'''nel subunit '''A'''Ipha '''1A''', which is a description of the protein coded for by the gene."<ref>{{cite web | url = https://www.cacna1a.org/what-is-cacna1a | title = The Science of CACNA1A | author = <!--Not stated--> | website = CACNA1A Foundation | access-date = 28 March 2021}}</ref>}}<ref name="Migraine Genetics"/> Mutations in ''CACNA1A'' have been associated with various neurologic disorders, including [[familial hemiplegic migraine]], [[episodic ataxia]] type 2, and [[spinocerebellar ataxia type 6]].<ref name="Migraine Genetics"/>
{{Infobox_gene}}
The '''Ca<sub>v</sub>2.1''' [[P-type calcium channel|P]]/[[Q-type calcium channel|Q]] [[voltage-dependent calcium channel]] is encoded by the {{gene|CACNA1A}} gene.


== Function ==
== 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.
"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."<ref name="NCBI">{{cite web | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=773 | title = CACNA1A | author = <!--Not stated--> | date = 16 March 2021 | website = Gene | publisher = [[National Center for Biotechnology Information]] | access-date = 28 March 2021}}</ref>


== Clinical significance ==
== Clinical significance ==


Mutations in this 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.<ref>{{cite journal | vauthors = Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA | title = The expanding spectrum of movement disorders in genetic epilepsies | journal = Developmental Medicine and Child Neurology | volume = 62 | issue = 2 | pages = 178–191 | date = February 2020 | pmid = 31784983 | doi = 10.1111/dmcn.14407 }}</ref>
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.<ref>{{cite journal | vauthors = Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA | title = The expanding spectrum of movement disorders in genetic epilepsies | journal = Developmental Medicine and Child Neurology | volume = 62 | issue = 2 | pages = 178–191 | date = February 2020 | pmid = 31784983 | doi = 10.1111/dmcn.14407 | s2cid = 208498567 | url = https://discovery.ucl.ac.uk/id/eprint/10088482/ }}</ref>


This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants have been described, however, the full-length nature of not all is known. 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.<ref>{{cite web | title = Entrez Gene: CACNA1A calcium channel, voltage-dependent, P/Q type, alpha 1A subunit| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=773| access-date = }}</ref>
"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."<ref name="NCBI"/>


== Interactions ==
== Interactions ==


Cav2.1 has been shown to [[Protein-protein interaction|interact]] with [[CACNB4]].<ref name=pmid9442082>{{cite journal | vauthors = Walker D, Bichet D, Campbell KP, De Waard M | title = A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit | journal = The Journal of Biological Chemistry | volume = 273 | issue = 4 | pages = 2361–7 | date = January 1998 | pmid = 9442082 | doi = 10.1074/jbc.273.4.2361 | doi-access = free }}</ref><ref name=pmid10212211>{{cite journal | vauthors = Walker D, Bichet D, Geib S, Mori E, Cornet V, Snutch TP, Mori Y, De Waard M | display-authors = 6 | title = A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 18 | pages = 12383–90 | date = April 1999 | pmid = 10212211 | doi = 10.1074/jbc.274.18.12383 | doi-access = free }}</ref>
Cav2.1 has been shown to [[Protein-protein interaction|interact]] with ''[[CACNB4]]''.<ref name=pmid9442082>{{cite journal | vauthors = Walker D, Bichet D, Campbell KP, De Waard M | title = A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit | journal = The Journal of Biological Chemistry | volume = 273 | issue = 4 | pages = 2361–7 | date = January 1998 | pmid = 9442082 | doi = 10.1074/jbc.273.4.2361 | doi-access = free }}</ref><ref name=pmid10212211>{{cite journal | vauthors = Walker D, Bichet D, Geib S, Mori E, Cornet V, Snutch TP, Mori Y, De Waard M | display-authors = 6 | title = A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 18 | pages = 12383–90 | date = April 1999 | pmid = 10212211 | doi = 10.1074/jbc.274.18.12383 | doi-access = free }}</ref>

==Notes==
{{notelist}}


== References ==
== References ==
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{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal | vauthors = Terwindt G, Kors E, Haan J, Vermeulen F, Van den Maagdenberg A, Frants R, Ferrari M | title = Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine | journal = Archives of Neurology | volume = 59 | issue = 6 | pages = 1016–8 | date = June 2002 | pmid = 12056940 | doi = 10.1001/archneur.59.6.1016 | doi-access = free }}
* {{cite journal | vauthors = Terwindt G, Kors E, Haan J, Vermeulen F, Van den Maagdenberg A, Frants R, Ferrari M | title = Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine | journal = Archives of Neurology | volume = 59 | issue = 6 | pages = 1016–8 | date = June 2002 | pmid = 12056940 | doi = 10.1001/archneur.59.6.1016 | doi-access = free }}
* {{cite journal | vauthors = Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J | title = International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 411–25 | date = December 2005 | pmid = 16382099 | doi = 10.1124/pr.57.4.5 }}
* {{cite journal | vauthors = Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J | title = International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 411–25 | date = December 2005 | pmid = 16382099 | doi = 10.1124/pr.57.4.5 | s2cid = 10386627 }}
* {{cite journal | vauthors = Perez-Reyes E, Castellano A, Kim HS, Bertrand P, Baggstrom E, Lacerda AE, Wei XY, Birnbaumer L | display-authors = 6 | title = Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel | journal = The Journal of Biological Chemistry | volume = 267 | issue = 3 | pages = 1792–7 | date = January 1992 | pmid = 1370480 | doi = }}
* {{cite journal | vauthors = Perez-Reyes E, Castellano A, Kim HS, Bertrand P, Baggstrom E, Lacerda AE, Wei XY, Birnbaumer L | display-authors = 6 | title = Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel | journal = The Journal of Biological Chemistry | volume = 267 | issue = 3 | pages = 1792–7 | date = January 1992 | doi = 10.1016/S0021-9258(18)46015-2 | pmid = 1370480 | doi-access = free }}
* {{cite journal | vauthors = Barry EL, Viglione MP, Kim YI, Froehner SC | title = Expression and antibody inhibition of P-type calcium channels in human small-cell lung carcinoma cells | journal = The Journal of Neuroscience | volume = 15 | issue = 1 Pt 1 | pages = 274–83 | date = January 1995 | pmid = 7823133 | doi = 10.1523/JNEUROSCI.15-01-00274.1995 | doi-access = free }}
* {{cite journal | vauthors = Barry EL, Viglione MP, Kim YI, Froehner SC | title = Expression and antibody inhibition of P-type calcium channels in human small-cell lung carcinoma cells | journal = The Journal of Neuroscience | volume = 15 | issue = 1 Pt 1 | pages = 274–83 | date = January 1995 | pmid = 7823133 | doi = 10.1523/JNEUROSCI.15-01-00274.1995 | pmc = 6578292 | doi-access = free }}
* {{cite journal | vauthors = Joutel A, Bousser MG, Biousse V, Labauge P, Chabriat H, Nibbio A, Maciazek J, Meyer B, Bach MA, Weissenbach J | display-authors = 6 | title = A gene for familial hemiplegic migraine maps to chromosome 19 | journal = Nature Genetics | volume = 5 | issue = 1 | pages = 40–5 | date = September 1993 | pmid = 8220421 | doi = 10.1038/ng0993-40 }}
* {{cite journal | vauthors = Joutel A, Bousser MG, Biousse V, Labauge P, Chabriat H, Nibbio A, Maciazek J, Meyer B, Bach MA, Weissenbach J | display-authors = 6 | title = A gene for familial hemiplegic migraine maps to chromosome 19 | journal = Nature Genetics | volume = 5 | issue = 1 | pages = 40–5 | date = September 1993 | pmid = 8220421 | doi = 10.1038/ng0993-40 | s2cid = 6493091 }}
* {{cite journal | vauthors = Margolis RL, Breschel TS, Li SH, Kidwai AS, Antonarakis SE, McInnis MG, Ross CA | title = Characterization of cDNA clones containing CCA trinucleotide repeats derived from human brain | journal = Somatic Cell and Molecular Genetics | volume = 21 | issue = 4 | pages = 279–84 | date = July 1995 | pmid = 8525433 | doi = 10.1007/BF02255782 }}
* {{cite journal | vauthors = Margolis RL, Breschel TS, Li SH, Kidwai AS, Antonarakis SE, McInnis MG, Ross CA | title = Characterization of cDNA clones containing CCA trinucleotide repeats derived from human brain | journal = Somatic Cell and Molecular Genetics | volume = 21 | issue = 4 | pages = 279–84 | date = July 1995 | pmid = 8525433 | doi = 10.1007/BF02255782 | s2cid = 22174220 }}
* {{cite journal | vauthors = Rettig J, Sheng ZH, Kim DK, Hodson CD, Snutch TP, Catterall WA | title = Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 14 | pages = 7363–8 | date = July 1996 | pmid = 8692999 | pmc = 38990 | doi = 10.1073/pnas.93.14.7363 }}
* {{cite journal | vauthors = Rettig J, Sheng ZH, Kim DK, Hodson CD, Snutch TP, Catterall WA | title = Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 14 | pages = 7363–8 | date = July 1996 | pmid = 8692999 | pmc = 38990 | doi = 10.1073/pnas.93.14.7363 | bibcode = 1996PNAS...93.7363R | doi-access = free }}
* {{cite journal | vauthors = Diriong S, Lory P, Williams ME, Ellis SB, Harpold MM, Taviaux S | title = Chromosomal localization of the human genes for alpha 1A, alpha 1B, and alpha 1E voltage-dependent Ca2+ channel subunits | journal = Genomics | volume = 30 | issue = 3 | pages = 605–9 | date = December 1995 | pmid = 8825650 | doi = 10.1006/geno.1995.1284 }}
* {{cite journal | vauthors = Diriong S, Lory P, Williams ME, Ellis SB, Harpold MM, Taviaux S | title = Chromosomal localization of the human genes for alpha 1A, alpha 1B, and alpha 1E voltage-dependent Ca2+ channel subunits | journal = Genomics | volume = 30 | issue = 3 | pages = 605–9 | date = December 1995 | pmid = 8825650 | doi = 10.1006/geno.1995.1284 }}
* {{cite journal | vauthors = Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M, Haan J, Lindhout D, van Ommen GJ, Hofker MH, Ferrari MD, Frants RR | display-authors = 6 | title = Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4 | journal = Cell | volume = 87 | issue = 3 | pages = 543–52 | date = November 1996 | pmid = 8898206 | doi = 10.1016/S0092-8674(00)81373-2 }}
* {{cite journal | vauthors = Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M, Haan J, Lindhout D, van Ommen GJ, Hofker MH, Ferrari MD, Frants RR | display-authors = 6 | title = Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4 | journal = Cell | volume = 87 | issue = 3 | pages = 543–52 | date = November 1996 | pmid = 8898206 | doi = 10.1016/S0092-8674(00)81373-2 | hdl = 1765/57576 | s2cid = 16840573 | hdl-access = free }}
* {{cite journal | vauthors = Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, Dobyns WB, Subramony SH, Zoghbi HY, Lee CC | display-authors = 6 | title = Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel | journal = Nature Genetics | volume = 15 | issue = 1 | pages = 62–9 | date = January 1997 | pmid = 8988170 | doi = 10.1038/ng0197-62 }}
* {{cite journal | vauthors = Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, Dobyns WB, Subramony SH, Zoghbi HY, Lee CC | display-authors = 6 | title = Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel | journal = Nature Genetics | volume = 15 | issue = 1 | pages = 62–9 | date = January 1997 | pmid = 8988170 | doi = 10.1038/ng0197-62 | s2cid = 9116828 }}
* {{cite journal | vauthors = De Waard M, Liu H, Walker D, Scott VE, Gurnett CA, Campbell KP | title = Direct binding of G-protein betagamma complex to voltage-dependent calcium channels | journal = Nature | volume = 385 | issue = 6615 | pages = 446–50 | date = January 1997 | pmid = 9009193 | doi = 10.1038/385446a0 }}
* {{cite journal |author5-link=Christina Gurnett | vauthors = De Waard M, Liu H, Walker D, Scott VE, Gurnett CA, Campbell KP | title = Direct binding of G-protein betagamma complex to voltage-dependent calcium channels | journal = Nature | volume = 385 | issue = 6615 | pages = 446–50 | date = January 1997 | pmid = 9009193 | doi = 10.1038/385446a0 | bibcode = 1997Natur.385..446W | s2cid = 4287544 }}
* {{cite journal | vauthors = Qin N, Platano D, Olcese R, Stefani E, Birnbaumer L | title = 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 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 16 | pages = 8866–71 | date = August 1997 | pmid = 9238069 | pmc = 23172 | doi = 10.1073/pnas.94.16.8866 }}
* {{cite journal | vauthors = Qin N, Platano D, Olcese R, Stefani E, Birnbaumer L | title = 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 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 16 | pages = 8866–71 | date = August 1997 | pmid = 9238069 | pmc = 23172 | doi = 10.1073/pnas.94.16.8866 | doi-access = free }}
* {{cite journal | vauthors = Riess O, Schöls L, Bottger H, Nolte D, Vieira-Saecker AM, Schimming C, Kreuz F, Macek M, Krebsová A, Klockgether T, Zühlke C, Laccone FA | display-authors = 6 | title = SCA6 is caused by moderate CAG expansion in the alpha1A-voltage-dependent calcium channel gene | journal = Human Molecular Genetics | volume = 6 | issue = 8 | pages = 1289–93 | date = August 1997 | pmid = 9259275 | doi = 10.1093/hmg/6.8.1289 | doi-access = free }}
* {{cite journal | vauthors = Riess O, Schöls L, Bottger H, Nolte D, Vieira-Saecker AM, Schimming C, Kreuz F, Macek M, Krebsová A, Klockgether T, Zühlke C, Laccone FA | display-authors = 6 | title = SCA6 is caused by moderate CAG expansion in the alpha1A-voltage-dependent calcium channel gene | journal = Human Molecular Genetics | volume = 6 | issue = 8 | pages = 1289–93 | date = August 1997 | pmid = 9259275 | doi = 10.1093/hmg/6.8.1289 | doi-access = free }}
* {{cite journal | vauthors = Jodice C, Mantuano E, Veneziano L, Trettel F, Sabbadini G, Calandriello L, Francia A, Spadaro M, Pierelli F, Salvi F, Ophoff RA, Frants RR, Frontali M | display-authors = 6 | title = Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p | journal = Human Molecular Genetics | volume = 6 | issue = 11 | pages = 1973–8 | date = October 1997 | pmid = 9302278 | doi = 10.1093/hmg/6.11.1973 | doi-access = free }}
* {{cite journal | vauthors = Jodice C, Mantuano E, Veneziano L, Trettel F, Sabbadini G, Calandriello L, Francia A, Spadaro M, Pierelli F, Salvi F, Ophoff RA, Frants RR, Frontali M | display-authors = 6 | title = Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p | journal = Human Molecular Genetics | volume = 6 | issue = 11 | pages = 1973–8 | date = October 1997 | pmid = 9302278 | doi = 10.1093/hmg/6.11.1973 | doi-access = free | hdl = 2108/35797 | hdl-access = free }}
* {{cite journal | vauthors = Charvin N, L'evêque C, Walker D, Berton F, Raymond C, Kataoka M, Shoji-Kasai Y, Takahashi M, De Waard M, Seagar MJ | display-authors = 6 | title = Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel | journal = The EMBO Journal | volume = 16 | issue = 15 | pages = 4591–6 | date = August 1997 | pmid = 9303303 | pmc = 1170085 | doi = 10.1093/emboj/16.15.4591 }}
* {{cite journal | vauthors = Charvin N, L'evêque C, Walker D, Berton F, Raymond C, Kataoka M, Shoji-Kasai Y, Takahashi M, De Waard M, Seagar MJ | display-authors = 6 | title = Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel | journal = The EMBO Journal | volume = 16 | issue = 15 | pages = 4591–6 | date = August 1997 | pmid = 9303303 | pmc = 1170085 | doi = 10.1093/emboj/16.15.4591 }}
* {{cite journal | vauthors = Ishikawa K, Tanaka H, Saito M, Ohkoshi N, Fujita T, Yoshizawa K, Ikeuchi T, Watanabe M, Hayashi A, Takiyama Y, Nishizawa M, Nakano I, Matsubayashi K, Miwa M, Shoji S, Kanazawa I, Tsuji S, Mizusawa H | display-authors = 6 | title = 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 | journal = American Journal of Human Genetics | volume = 61 | issue = 2 | pages = 336–46 | date = August 1997 | pmid = 9311738 | pmc = 1715894 | doi = 10.1086/514867 }}
* {{cite journal | vauthors = Ishikawa K, Tanaka H, Saito M, Ohkoshi N, Fujita T, Yoshizawa K, Ikeuchi T, Watanabe M, Hayashi A, Takiyama Y, Nishizawa M, Nakano I, Matsubayashi K, Miwa M, Shoji S, Kanazawa I, Tsuji S, Mizusawa H | display-authors = 6 | title = 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 | journal = American Journal of Human Genetics | volume = 61 | issue = 2 | pages = 336–46 | date = August 1997 | pmid = 9311738 | pmc = 1715894 | doi = 10.1086/514867 }}
* {{cite journal | vauthors = Walker D, Bichet D, Campbell KP, De Waard M | title = A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit | journal = The Journal of Biological Chemistry | volume = 273 | issue = 4 | pages = 2361–7 | date = January 1998 | pmid = 9442082 | doi = 10.1074/jbc.273.4.2361 | doi-access = free }}
* {{cite journal | vauthors = Walker D, Bichet D, Campbell KP, De Waard M | title = A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit | journal = The Journal of Biological Chemistry | volume = 273 | issue = 4 | pages = 2361–7 | date = January 1998 | pmid = 9442082 | doi = 10.1074/jbc.273.4.2361 | doi-access = free }}
* {{cite journal | vauthors = Yue Q, Jen JC, Thwe MM, Nelson SF, Baloh RW | title = De novo mutation in CACNA1A caused acetazolamide-responsive episodic ataxia | journal = American Journal of Medical Genetics | volume = 77 | issue = 4 | pages = 298–301 | date = May 1998 | pmid = 9600739 | doi = 10.1002/(SICI)1096-8628(19980526)77:4<298::AID-AJMG9>3.0.CO;2-J }}
* {{cite journal | vauthors = Yue Q, Jen JC, Thwe MM, Nelson SF, Baloh RW | title = De novo mutation in CACNA1A caused acetazolamide-responsive episodic ataxia | journal = American Journal of Medical Genetics | volume = 77 | issue = 4 | pages = 298–301 | date = May 1998 | pmid = 9600739 | doi = 10.1002/(SICI)1096-8628(19980526)77:4<298::AID-AJMG9>3.0.CO;2-J }}
* {{cite journal | vauthors = Hans M, Urrutia A, Deal C, Brust PF, Stauderman K, Ellis SB, Harpold MM, Johnson EC, Williams ME | display-authors = 6 | title = Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels | journal = Biophysical Journal | volume = 76 | issue = 3 | pages = 1384–400 | date = March 1999 | pmid = 10049321 | pmc = 1300117 | doi = 10.1016/S0006-3495(99)77300-5 }}
* {{cite journal | vauthors = Hans M, Urrutia A, Deal C, Brust PF, Stauderman K, Ellis SB, Harpold MM, Johnson EC, Williams ME | display-authors = 6 | title = Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels | journal = Biophysical Journal | volume = 76 | issue = 3 | pages = 1384–400 | date = March 1999 | pmid = 10049321 | pmc = 1300117 | doi = 10.1016/S0006-3495(99)77300-5 | bibcode = 1999BpJ....76.1384H }}
* {{cite journal | vauthors = Walker D, Bichet D, Geib S, Mori E, Cornet V, Snutch TP, Mori Y, De Waard M | display-authors = 6 | title = A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 18 | pages = 12383–90 | date = April 1999 | pmid = 10212211 | doi = 10.1074/jbc.274.18.12383 | doi-access = free }}
* {{cite journal | vauthors = Walker D, Bichet D, Geib S, Mori E, Cornet V, Snutch TP, Mori Y, De Waard M | display-authors = 6 | title = A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 18 | pages = 12383–90 | date = April 1999 | pmid = 10212211 | doi = 10.1074/jbc.274.18.12383 | doi-access = free }}
{{refend}}
{{refend}}
* {{cite journal |first1=Yuliia V. |last1=Nikonishyna |display-authors=et al. |title=Novel CACNA1A Variant p.Cys256Phe Disrupts Disulfide Bonds and Causes Spinocerebellar Ataxia |journal=Movement Disorders |year=2022 |volume=37 |issue=2 |pages=401–404 |publisher=Movement disorders: official journal of the Movement Disorder Society |doi=10.1002/mds.28835 |pmid=34647648 |s2cid=238859984 |doi-access=free }}


== Further reading ==
== Further reading ==
{{refbegin}}
{{refbegin}}
* {{cite book |first=Joanna C |last=Jen | name-list-format = vanc |date = May 2015 | chapter =Familial Hemiplegic Migraine |id=NBK1388 | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK1388/ |veditors=Pagon RA, Bird TD, Dolan CR |title=GeneReviews &#x5B;Internet&#x5D; |year=1993 |publisher=University of Washington, Seattle |location=Seattle WA |url=https://www.ncbi.nlm.nih.gov/books/n/gene/TOC/ |ref={{harvid|GeneReviews}}|display-editors=etal}}
* {{cite book |first=Joanna C |last=Jen |date = May 2015 | chapter =Familial Hemiplegic Migraine |id=NBK1388 | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK1388/ |veditors=Pagon RA, Bird TD, Dolan CR |title=GeneReviews |origyear=1993 |publisher=University of Washington, Seattle |location=Seattle WA |pmid=20301295 |url=https://www.ncbi.nlm.nih.gov/books/n/gene/TOC/ |ref={{harvid|GeneReviews}}|display-editors=etal}}
* {{cite book |first=Sian |last=Spacey | name-list-format = vanc |date= December 2011 |title=Episodic Ataxia Type 2 |id=NBK1501 |url=https://www.ncbi.nlm.nih.gov/books/NBK1501/ }} In {{harvnb|GeneReviews}}
* {{cite book |first=Sian |last=Spacey |date= December 2011 |title=Episodic Ataxia Type 2 |chapter=Episodic Ataxia Type 2 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY |publisher=University of Washington, Seattle |pmid=20301674 |id=NBK1501 |url=https://www.ncbi.nlm.nih.gov/books/NBK1501/ }} In {{harvnb|GeneReviews}}
* {{cite book |first=Christopher M |last=Gomez | name-list-format = vanc |date= July 2013 |title=Spinocerebellar Ataxia Type 6 |id=NBK1140 |url=https://www.ncbi.nlm.nih.gov/books/NBK1140/ }} In {{harvnb|GeneReviews}}
* {{cite book |first=Christopher M |last=Gomez |date= July 2013 |title=Spinocerebellar Ataxia Type 6 |publisher=University of Washington, Seattle |pmid=20301319 |id=NBK1140 |url=https://www.ncbi.nlm.nih.gov/books/NBK1140/ }} In {{harvnb|GeneReviews}}
{{refend}}
{{refend}}
* {{MeshName|CACNA1A+protein,+human}}
* {{MeshName|CACNA1A+protein,+human}}

Revision as of 18:35, 22 August 2024

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

773

12286

Ensembl

ENSG00000141837

ENSMUSG00000034656

UniProt

O00555

P97445

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

"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

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

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

Notes

  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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000141837 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034656 – 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. ^ 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

Further reading

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