ATP2A1

ATP2A1
Identifiers
Aliases	ATP2A1, ATP2A, SERCA1, ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1
External IDs	OMIM: 108730; MGI: 105058; HomoloGene: 7635; GeneCards: ATP2A1; OMA:ATP2A1 - orthologs
Gene location (Human) Chr. Chromosome 16 (human) Band 16p11.2 Start 28,878,405 bp End 28,904,466 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7 F3|7 69.04 cM Start 126,045,030 bp End 126,062,280 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in muscle of thigh Skeletal muscle tissue of rectus abdominis thoracic diaphragm Skeletal muscle tissue of biceps brachii vastus lateralis muscle triceps brachii muscle gastrocnemius muscle body of tongue glutes deltoid muscle Top expressed in ankle triceps brachii muscle temporal muscle sternocleidomastoid muscle digastric muscle muscle of thigh vastus lateralis muscle extensor digitorum longus muscle tibialis anterior muscle medial head of gastrocnemius muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding calcium ion binding protein homodimerization activity metal ion binding protein binding hydrolase activity ATP binding P-type calcium transporter activity ATPase activity P-type proton-exporting transporter activity Cellular component integral component of membrane endoplasmic reticulum membrane membrane I band calcium channel complex H zone sarcoplasmic reticulum platelet dense tubular network membrane endoplasmic reticulum sarcoplasmic reticulum membrane perinuclear region of cytoplasm endoplasmic reticulum-Golgi intermediate compartment mitochondrion Biological process regulation of cardiac conduction positive regulation of fast-twitch skeletal muscle fiber contraction negative regulation of striated muscle contraction calcium ion import positive regulation of endoplasmic reticulum calcium ion concentration ion transport response to endoplasmic reticulum stress maintenance of mitochondrion location ion transmembrane transport intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress regulation of striated muscle contraction apoptotic mitochondrial changes relaxation of skeletal muscle negative regulation of endoplasmic reticulum calcium ion concentration positive regulation of mitochondrial calcium ion concentration calcium ion transport calcium ion transmembrane transport cellular calcium ion homeostasis proton transmembrane transport calcium ion import into sarcoplasmic reticulum positive regulation of cardiac muscle cell contraction positive regulation of ATPase-coupled calcium transmembrane transporter activity positive regulation of calcium ion import into sarcoplasmic reticulum Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 487 11937 Ensembl ENSG00000196296 ENSMUSG00000030730 UniProt O14983 Q8R429 RefSeq (mRNA) NM_173201 NM_001286075 NM_004320 NM_007504 RefSeq (protein) NP_001273004 NP_004311 NP_775293 NP_031530 Location (UCSC) Chr 16: 28.88 – 28.9 Mb Chr 7: 126.05 – 126.06 Mb PubMed search
Wikidata
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Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) also known as Calcium pump 1, is an enzyme that in humans is encoded by the ATP2A1 gene.

Function

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.

Clinical significance

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.

Interactions

ATP2A1 has been shown to interact with:

• SLN, and
• PLN.

External links

• Human ATP2A1 genome location and ATP2A1 gene details page in the UCSC Genome Browser.

Further reading

• Baba-Aissa F, Raeymaekers L, Wuytack F, Dode L, Casteels R (Apr 1998). "Distribution and isoform diversity of the organellar Ca²⁺ pumps in the brain". Molecular and Chemical Neuropathology. 33 (3): 199–208. doi:10.1007/BF02815182. PMID 9642673.
• Callen DF, Baker E, Lane S, Nancarrow J, Thompson A, Whitmore SA, et al. (Dec 1991). "Regional mapping of the Batten disease locus (CLN3) to human chromosome 16p12". American Journal of Human Genetics. 49 (6): 1372–1377. PMC 1702406. PMID 1746562.
• MacLennan DH, Brandl CJ, Champaneria S, Holland PC, Powers VE, Willard HF (Jul 1987). "Fast-twitch and slow-twitch/cardiac Ca²⁺ ATPase genes map to human chromosomes 16 and 12". Somatic Cell and Molecular Genetics. 13 (4): 341–346. doi:10.1007/BF01534928. PMID 2842876. S2CID 1475105.
• Brandl CJ, Green NM, Korczak B, MacLennan DH (Feb 1986). "Two Ca²⁺ ATPase genes: homologies and mechanistic implications of deduced amino acid sequences". Cell. 44 (4): 597–607. doi:10.1016/0092-8674(86)90269-2. PMID 2936465. S2CID 43419264.
• Benders AA, Wevers RA, Veerkamp JH (Mar 1996). "Ion transport in human skeletal muscle cells: disturbances in myotonic dystrophy and Brody's disease". Acta Physiologica Scandinavica. 156 (3): 355–367. doi:10.1046/j.1365-201X.1996.202000.x. hdl:2066/24180. PMID 8729696.
• Zhang Y, Fujii J, Phillips MS, Chen HS, Karpati G, Yee WC, et al. (Dec 1995). "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". Genomics. 30 (3): 415–424. doi:10.1006/geno.1995.1259. PMID 8825625.
• Odermatt A, Taschner PE, Khanna VK, Busch HF, Karpati G, Jablecki CK, et al. (Oct 1996). "Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca²⁺ ATPase, are associated with Brody disease". Nature Genetics. 14 (2): 191–194. doi:10.1038/ng1096-191. PMID 8841193. S2CID 22726202.
• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Algenstaedt P, Antonetti DA, Yaffe MB, Kahn CR (Sep 1997). "Insulin receptor substrate proteins create a link between the tyrosine phosphorylation cascade and the Ca²⁺-ATPases in muscle and heart". Journal of Biological Chemistry. 272 (38): 23696–23702. doi:10.1074/jbc.272.38.23696. PMID 9295312.
• Odermatt A, Taschner PE, Scherer SW, Beatty B, Khanna VK, Cornblath DR, et al. (Nov 1997). "Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: absence of structural mutations in five patients with Brody disease". Genomics. 45 (3): 541–553. doi:10.1006/geno.1997.4967. hdl:2066/25426. PMID 9367679. S2CID 41989102.
• MacLennan DH, Rice WJ, Odermatt A (Nov 1997). "Structure/function analysis of the Ca²⁺ binding and translocation domain of SERCA1 and the role in Brody disease of the ATP2A1 gene encoding SERCA1". Annals of the New York Academy of Sciences. 834 (1 Na/K–ATPase a): 175–185. doi:10.1111/j.1749-6632.1997.tb52249.x. PMID 9405806. S2CID 38068023.
• Odermatt A, Becker S, Khanna VK, Kurzydlowski K, Leisner E, Pette D, et al. (May 1998). "Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca²⁺-ATPase". Journal of Biological Chemistry. 273 (20): 12360–12369. doi:10.1074/jbc.273.20.12360. PMID 9575189.
• Asahi M, Kimura Y, Kurzydlowski K, Tada M, MacLennan DH (Nov 1999). "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 of Biological Chemistry. 274 (46): 32855–32862. doi:10.1074/jbc.274.46.32855. PMID 10551848.
• Odermatt A, Barton K, Khanna VK, Mathieu J, Escolar D, Kuntzer T, et al. (May 2000). "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". Human Genetics. 106 (5): 482–491. doi:10.1007/s004390000297. PMID 10914677. S2CID 31756080.
• Daiho T, Yamasaki K, Saino T, Kamidochi M, Satoh K, Iizuka H, et al. (Aug 2001). "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 of Biological Chemistry. 276 (35): 32771–32778. doi:10.1074/jbc.M101229200. PMID 11438520.
• Asahi M, Green NM, Kurzydlowski K, Tada M, MacLennan DH (Aug 2001). "Phospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca²⁺ ATPases". Proceedings of the National Academy of Sciences of the United States of America. 98 (18): 10061–10066. Bibcode:2001PNAS...9810061A. doi:10.1073/pnas.181348298. PMC 56915. PMID 11526231.
• Pieske B, Maier LS, Schmidt-Schweda S (2002). "Sarcoplasmic reticulum Ca²⁺ load in human heart failure". Basic Research in Cardiology. 97 Suppl 1 (7): I63 – I71. doi:10.1007/s003950200032. PMID 12479237. S2CID 22854208.
• Toyoshima C, Asahi M, Sugita Y, Khanna R, Tsuda T, MacLennan DH (Jan 2003). "Modeling of the inhibitory interaction of phospholamban with the Ca²⁺ ATPase". Proceedings of the National Academy of Sciences of the United States of America. 100 (2): 467–472. Bibcode:2003PNAS..100..467T. doi:10.1073/pnas.0237326100. PMC 141018. PMID 12525698.