ATP2A1

This gene encodes one of the SERCA Ca²⁺-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction.

Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in two transcript variants encoding different isoforms.

Alternative splicing of ATP2A1 is also implicated in myotonic dystrophy type 1.

ATP2A1 SERCA pumps were very strongly down regulated in amyotrophic lateral sclerosis.{{Cite journal | vauthors = Mukund K, Subramaniam S | title = Co-expression Network Approach Reveals Functional Similarities among Diseases Affecting Human Skeletal Muscle | journal = Frontiers in Physiology | volume = 8 | pages = 980 | year = 2017 | pmid = 29249983 | pmc = 5717538 | doi = 10.3389/fphys.2017.00980 | doi-access = free }}

ATP2A1 has been shown to interact with:

• SLN,{{cite journal | vauthors = Asahi M, Sugita Y, Kurzydlowski K, De Leon S, Tada M, Toyoshima C, MacLennan DH | title = Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 9 | pages = 5040–5045 | date = April 2003 | pmid = 12692302 | pmc = 154294 | doi = 10.1073/pnas.0330962100 | bibcode = 2003PNAS..100.5040A | doi-access = free }} and
• PLN.{{cite journal | vauthors = Asahi M, Kurzydlowski K, Tada M, MacLennan DH | title = Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) | journal = Journal of Biological Chemistry | volume = 277 | issue = 30 | pages = 26725–26728 | date = July 2002 | pmid = 12032137 | doi = 10.1074/jbc.C200269200 | doi-access = free }}{{cite journal | vauthors = Asahi M, Kimura Y, Kurzydlowski K, Tada M, MacLennan DH | title = Transmembrane helix M6 in sarco(endo)plasmic reticulum Ca(2+)-ATPase forms a functional interaction site with phospholamban. Evidence for physical interactions at other sites | journal = Journal of Biological Chemistry | volume = 274 | issue = 46 | pages = 32855–32862 | date = November 1999 | pmid = 10551848 | doi = 10.1074/jbc.274.46.32855 | doi-access = free }}{{cite journal | vauthors = Asahi M, Green NM, Kurzydlowski K, Tada M, MacLennan DH | title = Phospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca2+ ATPases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 18 | pages = 10061–10066 | date = August 2001 | pmid = 11526231 | pmc = 56915 | doi = 10.1073/pnas.181348298 | bibcode = 2001PNAS...9810061A | doi-access = free }}

{{Reflist}}

• {{UCSC gene info|ATP2A1}}

{{Refbegin | 2}}

• {{cite journal | vauthors = Baba-Aissa F, Raeymaekers L, Wuytack F, Dode L, Casteels R | title = Distribution and isoform diversity of the organellar Ca²⁺ pumps in the brain. | journal = Molecular and Chemical Neuropathology | volume = 33 | issue = 3 | pages = 199–208 | date = Apr 1998 | pmid = 9642673 | doi = 10.1007/BF02815182 }}
• {{cite journal | vauthors = Callen DF, Baker E, Lane S, Nancarrow J, Thompson A, Whitmore SA, MacLennan DH, Berger R, Cherif D, Jarvela I, et A | title = Regional mapping of the Batten disease locus (CLN3) to human chromosome 16p12. | journal = American Journal of Human Genetics | volume = 49 | issue = 6 | pages = 1372–1377 | date = Dec 1991 | pmid = 1746562 | pmc = 1702406 }}
• {{cite journal | vauthors = MacLennan DH, Brandl CJ, Champaneria S, Holland PC, Powers VE, Willard HF | title = Fast-twitch and slow-twitch/cardiac Ca²⁺ ATPase genes map to human chromosomes 16 and 12. | journal = Somatic Cell and Molecular Genetics | volume = 13 | issue = 4 | pages = 341–346 | date = Jul 1987 | pmid = 2842876 | doi = 10.1007/BF01534928 | s2cid = 1475105 }}
• {{cite journal | vauthors = Brandl CJ, Green NM, Korczak B, MacLennan DH | title = Two Ca²⁺ ATPase genes: homologies and mechanistic implications of deduced amino acid sequences. | journal = Cell | volume = 44 | issue = 4 | pages = 597–607 | date = Feb 1986 | pmid = 2936465 | doi = 10.1016/0092-8674(86)90269-2 | s2cid = 43419264 }}
• {{cite journal | vauthors = Benders AA, Wevers RA, Veerkamp JH | title = Ion transport in human skeletal muscle cells: disturbances in myotonic dystrophy and Brody's disease. | journal = Acta Physiologica Scandinavica | volume = 156 | issue = 3 | pages = 355–367 | date = Mar 1996 | pmid = 8729696 | doi = 10.1046/j.1365-201X.1996.202000.x | hdl = 2066/24180 | hdl-access = free }}
• {{cite journal | vauthors = Zhang Y, Fujii J, Phillips MS, Chen HS, Karpati G, Yee WC, Schrank B, Cornblath DR, Boylan KB, MacLennan DH | title = Characterization of cDNA and genomic DNA encoding SERCA1, the Ca²⁺-ATPase of human fast-twitch skeletal muscle sarcoplasmic reticulum, and its elimination as a candidate gene for Brody disease. | journal = Genomics | volume = 30 | issue = 3 | pages = 415–424 | date = Dec 1995 | pmid = 8825625 | doi = 10.1006/geno.1995.1259 | doi-access = free }}
• {{cite journal | vauthors = Odermatt A, Taschner PE, Khanna VK, Busch HF, Karpati G, Jablecki CK, Breuning MH, MacLennan DH | title = Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca²⁺ ATPase, are associated with Brody disease. | journal = Nature Genetics | volume = 14 | issue = 2 | pages = 191–194 | date = Oct 1996 | pmid = 8841193 | doi = 10.1038/ng1096-191 | s2cid = 22726202 }}
• {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery. | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }}
• {{cite journal | vauthors = Algenstaedt P, Antonetti DA, Yaffe MB, Kahn CR | title = Insulin receptor substrate proteins create a link between the tyrosine phosphorylation cascade and the Ca²⁺-ATPases in muscle and heart. | journal = Journal of Biological Chemistry | volume = 272 | issue = 38 | pages = 23696–23702 | date = Sep 1997 | pmid = 9295312 | doi = 10.1074/jbc.272.38.23696 | doi-access = free }}
• {{cite journal | vauthors = Odermatt A, Taschner PE, Scherer SW, Beatty B, Khanna VK, Cornblath DR, Chaudhry V, Yee WC, Schrank B, Karpati G, Breuning MH, Knoers N, MacLennan DH | title = Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: absence of structural mutations in five patients with Brody disease. | journal = Genomics | volume = 45 | issue = 3 | pages = 541–553 | date = Nov 1997 | pmid = 9367679 | doi = 10.1006/geno.1997.4967 | hdl = 2066/25426 | s2cid = 41989102 | url = http://repub.eur.nl/pub/59319 | hdl-access = free }}
• {{cite journal | vauthors = MacLennan DH, Rice WJ, Odermatt A | title = Structure/function analysis of the Ca²⁺ binding and translocation domain of SERCA1 and the role in Brody disease of the ATP2A1 gene encoding SERCA1. | journal = Annals of the New York Academy of Sciences | volume = 834 | issue = 1 Na/K–ATPase a | pages = 175–185 | date = Nov 1997 | pmid = 9405806 | doi = 10.1111/j.1749-6632.1997.tb52249.x | s2cid = 38068023 }}
• {{cite journal | vauthors = Odermatt A, Becker S, Khanna VK, Kurzydlowski K, Leisner E, Pette D, MacLennan DH | title = Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca²⁺-ATPase. | journal = Journal of Biological Chemistry | volume = 273 | issue = 20 | pages = 12360–12369 | date = May 1998 | pmid = 9575189 | doi = 10.1074/jbc.273.20.12360 | doi-access = free }}
• {{cite journal | vauthors = Asahi M, Kimura Y, Kurzydlowski K, Tada M, MacLennan DH | title = Transmembrane helix M6 in sarco(endo)plasmic reticulum Ca²⁺-ATPase forms a functional interaction site with phospholamban. Evidence for physical interactions at other sites. | journal = Journal of Biological Chemistry | volume = 274 | issue = 46 | pages = 32855–32862 | date = Nov 1999 | pmid = 10551848 | doi = 10.1074/jbc.274.46.32855 | doi-access = free }}
• {{cite journal | vauthors = Odermatt A, Barton K, Khanna VK, Mathieu J, Escolar D, Kuntzer T, Karpati G, MacLennan DH | title = The mutation of Pro789 to Leu reduces the activity of the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca²⁺ ATPase (SERCA1) and is associated with Brody disease. | journal = Human Genetics | volume = 106 | issue = 5 | pages = 482–491 | date = May 2000 | pmid = 10914677 | doi = 10.1007/s004390000297 | s2cid = 31756080 }}
• {{cite journal | vauthors = Daiho T, Yamasaki K, Saino T, Kamidochi M, Satoh K, Iizuka H, Suzuki H | title = Mutations of either or both Cys876 and Cys888 residues of sarcoplasmic reticulum Ca²⁺ATPase result in a complete loss of Ca²⁺ transport activity without a loss of Ca²⁺-dependent ATPase activity. Role of the CYS876-CYS888 disulfide bond. | journal = Journal of Biological Chemistry | volume = 276 | issue = 35 | pages = 32771–32778 | date = Aug 2001 | pmid = 11438520 | doi = 10.1074/jbc.M101229200 | doi-access = free }}
• {{cite journal | vauthors = Asahi M, Green NM, Kurzydlowski K, Tada M, MacLennan DH | title = Phospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca²⁺ ATPases. | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 18 | pages = 10061–10066 | date = Aug 2001 | pmid = 11526231 | pmc = 56915 | doi = 10.1073/pnas.181348298 | bibcode = 2001PNAS...9810061A | doi-access = free }}
• {{cite journal | vauthors = Pieske B, Maier LS, Schmidt-Schweda S | title = Sarcoplasmic reticulum Ca²⁺ load in human heart failure. | journal = Basic Research in Cardiology | volume = 97 Suppl 1 | issue = 7 | pages = I63–I71 | year = 2002 | pmid = 12479237 | doi = 10.1007/s003950200032 | s2cid = 22854208 }}
• {{cite journal | vauthors = Toyoshima C, Asahi M, Sugita Y, Khanna R, Tsuda T, MacLennan DH | title = Modeling of the inhibitory interaction of phospholamban with the Ca²⁺ ATPase. | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 2 | pages = 467–472 | date = Jan 2003 | pmid = 12525698 | pmc = 141018 | doi = 10.1073/pnas.0237326100 | bibcode = 2003PNAS..100..467T | doi-access = free }}

{{Refend}}

{{PDB Gallery|geneid=487}}

{{ATPases}}

{{Gene-16-stub}}