ATP2A1

Identifiers

ATP2A1, ATP2A, SERCA1, ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1

External IDs

MGI: 105058 HomoloGene: 7635 GeneCards: ATP2A1

Gene ontology
Molecular function	• nucleotide binding • calcium ion binding • protein homodimerization activity • metal ion binding • protein binding • hydrolase activity • ATP binding • calcium-transporting ATPase activity • ATPase 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 • ATP hydrolysis coupled cation transmembrane transport • transport
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

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: 126.45 – 126.46 Mb

PubMed search

^[1]

^[2]

Wikidata

View/Edit Human

View/Edit Mouse

Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 is an enzyme that in humans is encoded by the ATP2A1 gene.^[3]

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.^[3]

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.^[3]

Interactions

ATP2A1 has been shown to interact with:

SLN,^[4]^[5] and
PLN.^[4]^[6]^[7]

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
1 2 3 "Entrez Gene: ATP2A1 ATPase, Ca⁺⁺ transporting, cardiac muscle, fast twitch 1".
1 2 Asahi M, Kurzydlowski K, Tada M, MacLennan DH (July 2002). "Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs)". J. Biol. Chem. 277 (30): 26725–8. PMID 12032137. doi:10.1074/jbc.C200269200.
↑ Asahi M, Sugita Y, Kurzydlowski K, De Leon S, Tada M, Toyoshima C, MacLennan DH (April 2003). "Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban". Proc. Natl. Acad. Sci. U.S.A. 100 (9): 5040–5. PMC 154294 . PMID 12692302. doi:10.1073/pnas.0330962100.
↑ Asahi M, Kimura Y, Kurzydlowski K, Tada M, MacLennan DH (November 1999). "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". J. Biol. Chem. 274 (46): 32855–62. PMID 10551848. doi:10.1074/jbc.274.46.32855.
↑ Asahi M, Green NM, Kurzydlowski K, Tada M, MacLennan DH (August 2001). "Phospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca2+ ATPases". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10061–6. PMC 56915 . PMID 11526231. doi:10.1073/pnas.181348298.

External links

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

Baba-Aissa F, Raeymaekers L, Wuytack F, et al. (1998). "Distribution and isoform diversity of the organellar Ca²⁺ pumps in the brain.". Mol. Chem. Neuropathol. 33 (3): 199–208. PMID 9642673. doi:10.1007/BF02815182.
Callen DF, Baker E, Lane S, et al. (1992). "Regional mapping of the Batten disease locus (CLN3) to human chromosome 16p12.". Am. J. Hum. Genet. 49 (6): 1372–7. PMC 1702406 . PMID 1746562.
MacLennan DH, Brandl CJ, Champaneria S, et al. (1988). "Fast-twitch and slow-twitch/cardiac Ca²⁺ ATPase genes map to human chromosomes 16 and 12.". Somat. Cell Mol. Genet. 13 (4): 341–6. PMID 2842876. doi:10.1007/BF01534928.
Brandl CJ, Green NM, Korczak B, MacLennan DH (1986). "Two Ca²⁺ ATPase genes: homologies and mechanistic implications of deduced amino acid sequences.". Cell. 44 (4): 597–607. PMID 2936465. doi:10.1016/0092-8674(86)90269-2.
Benders AA, Wevers RA, Veerkamp JH (1996). "Ion transport in human skeletal muscle cells: disturbances in myotonic dystrophy and Brody's disease.". Acta Physiol. Scand. 156 (3): 355–67. PMID 8729696. doi:10.1046/j.1365-201X.1996.202000.x.
Zhang Y, Fujii J, Phillips MS, et al. (1997). "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): 415–24. PMID 8825625. doi:10.1006/geno.1995.1259.
Odermatt A, Taschner PE, Khanna VK, et al. (1996). "Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca²⁺ ATPase, are associated with Brody disease.". Nat. Genet. 14 (2): 191–4. PMID 8841193. doi:10.1038/ng1096-191.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. PMID 8889548. doi:10.1101/gr.6.9.791.
Algenstaedt P, Antonetti DA, Yaffe MB, Kahn CR (1997). "Insulin receptor substrate proteins create a link between the tyrosine phosphorylation cascade and the Ca²⁺-ATPases in muscle and heart.". J. Biol. Chem. 272 (38): 23696–702. PMID 9295312. doi:10.1074/jbc.272.38.23696.
Odermatt A, Taschner PE, Scherer SW, et al. (1998). "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): 541–53. PMID 9367679. doi:10.1006/geno.1997.4967.
MacLennan DH, Rice WJ, Odermatt A (1998). "Structure/function analysis of the Ca²⁺ binding and translocation domain of SERCA1 and the role in Brody disease of the ATP2A1 gene encoding SERCA1.". Ann. N. Y. Acad. Sci. 834: 175–85. PMID 9405806. doi:10.1111/j.1749-6632.1997.tb52249.x.
Odermatt A, Becker S, Khanna VK, et al. (1998). "Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca²⁺-ATPase.". J. Biol. Chem. 273 (20): 12360–9. PMID 9575189. doi:10.1074/jbc.273.20.12360.
Asahi M, Kimura Y, Kurzydlowski K, et al. (2000). "Transmembrane helix M6 in sarco(endo)plasmic reticulum Ca²⁺-ATPase forms a functional interaction site with phospholamban. Evidence for physical interactions at other sites.". J. Biol. Chem. 274 (46): 32855–62. PMID 10551848. doi:10.1074/jbc.274.46.32855.
Odermatt A, Barton K, Khanna VK, et al. (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.". Hum. Genet. 106 (5): 482–91. PMID 10914677. doi:10.1007/s004390000297.
Daiho T, Yamasaki K, Saino T, et al. (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.". J. Biol. Chem. 276 (35): 32771–8. PMID 11438520. doi:10.1074/jbc.M101229200.
Asahi M, Green NM, Kurzydlowski K, et al. (2001). "Phospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca²⁺ ATPases.". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10061–6. PMC 56915 . PMID 11526231. doi:10.1073/pnas.181348298.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.
Pieske B, Maier LS, Schmidt-Schweda S (2002). "Sarcoplasmic reticulum Ca²⁺ load in human heart failure.". Basic Res. Cardiol. 97 Suppl 1: I63–71. PMID 12479237.
Toyoshima C, Asahi M, Sugita Y, et al. (2003). "Modeling of the inhibitory interaction of phospholamban with the Ca²⁺ ATPase.". Proc. Natl. Acad. Sci. U.S.A. 100 (2): 467–72. PMC 141018 . PMID 12525698. doi:10.1073/pnas.0237326100.

PDB gallery

1iwo: Crystal structure of the SR Ca2+-ATPase in the absence of Ca2+

1kju: Ca2+-ATPase in the E2 State

1su4: Crystal structure of calcium ATPase with two bound calcium ions

1t5s: Structure of the (SR)Ca2+-ATPase Ca2-E1-AMPPCP form

1t5t: Structure of the (SR)Ca2+-ATPase Ca2-E1-ADP:AlF4- form

1vfp: Crystal structure of the SR CA2+-ATPase with bound AMPPCP

1wpe:

1wpg: Crystal structure of the SR CA2+-ATPase with MGF4

1xp5: Structure Of The (Sr)Ca2+-ATPase E2-AlF4- Form

2agv: Crystal structure of the SR CA2+-ATPASE with BHQ and TG

2by4: SR CA(2+)-ATPASE IN THE HNE2 STATE COMPLEXED WITH THE THAPSIGARGIN DERIVATIVE BOC-12ADT.

2c88: CRYSTAL STRUCTURE OF (SR) CALCIUM-ATPASE E2(TG):AMPPCP FORM

2c8k: CRYSTAL STRUCTURE OF (SR) CALCIUM-ATPASE E2(TG) WITH PARTIALLY OCCUPIED AMPPCP SITE

2c8l: CRYSTAL STRUCTURE OF (SR) CALCIUM-ATPASE E2(TG) FORM

2c9m: STRUCTURE OF (SR) CALCIUM-ATPASE IN THE CA2E1 STATE SOLVED IN A P1 CRYSTAL FORM.

2dqs: Crystal structure of the calcium pump with amppcp in the absence of calcium

2ear: P21 crystal of the SR CA2+-ATPase with bound TG

2eas: Crystal structure of the SR CA2+-ATPASE with bound CPA

2eat: Crystal structure of the SR CA2+-ATPASE with bound CPA and TG

2eau: Crystal structure of the SR CA2+-ATPASE with bound CPA in the presence of curcumin

2o9j: Crystal structure of calcium atpase with bound magnesium fluoride and cyclopiazonic acid

2oa0: Crystal structure of Calcium ATPase with bound ADP and cyclopiazonic acid

Hydrolases: acid anhydride hydrolases (EC 3.6)

3.6.1

3.6.2

3.6.3-4: ATPase

3.6.3

Cu++ (3.6.3.4)	Menkes/ATP7A Wilson/ATP7B
Ca+ (3.6.3.8)	SERCA ATP2A1 ATP2A2 ATP2A3 Plasma membrane ATP2B1 ATP2B2 ATP2B3 ATP2B4 SPCA ATP2C1 ATP2C2
Na+/K+ (3.6.3.9)	ATP1A1 ATP1A2 ATP1A3 ATP1A4 ATP1B1 ATP1B2 ATP1B3 ATP1B4
H+/K+ (3.6.3.10)	ATP4A
Other P-type ATPase	ATP8B1 ATP10A ATP11B ATP12A ATP13A2 ATP13A3

3.6.4

3.6.5: GTPase

3.6.5.1: Heterotrimeric G protein	G_αs G_αi GNAI1 GNAI2 GNAI3 G_αq/11 GNAQ GNA11 G_α12/13 GNA12 GNA13 Transducin GNAT1 GNAT2 Gustducin GNAT3
3.6.5.2: Small GTPase > Ras superfamily	Rho family of GTPases: Cdc42 CDC42 TC10 TCL RhoUV RhoU RhoV Rac Rac1 2 3 RhoG RhoBTB 1 2 RhoH Rho A B C Rnd 1 2 3 RhoDF RhoF RhoD other: Ras HRAS KRAS NRAS Rab RAB23 RAB27 Arf ARF6 SAR1B ARL13B ARL6 Ran Rheb Rap RGK
3.6.5.3: Protein-synthesizing GTPase	Prokaryotic IF-2 EF-Tu EF-G Eukaryotic
3.6.5.5-6: Polymerization motors	Dynamin Tubulin

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