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ATP2A1 - Wikipedia

From Wikipedia, the free encyclopedia

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)^[1]

Band	16p11.2	Start	28,878,405 bp^[1]
Band	16p11.2	End	28,904,466 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 7 (mouse)^[2]

Band	7 F3\|7 69.04 cM	Start	126,045,030 bp^[2]
Band	7 F3\|7 69.04 cM	End	126,062,280 bp^[2]

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

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

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.^[5]^[6]

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.^[5]

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.^[5] Alternative splicing of ATP2A1 is also implicated in myotonic dystrophy type 1.

ATP2A1 SERCA pumps were very strongly down regulated in amyotrophic lateral sclerosis.^[7]

Interactions

ATP2A1 has been shown to interact with:

SLN,^[8]^[9] and
PLN.^[8]^[10]^[11]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000196296 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030730 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c "Entrez Gene: ATP2A1 ATPase, Ca⁺⁺ transporting, cardiac muscle, fast twitch 1".
^ "UniProt". www.uniprot.org. Retrieved 1 August 2023.
^ Mukund, Kavitha; Subramaniam, Shankar (2017). "Co-expression Network Approach Reveals Functional Similarities among Diseases Affecting Human Skeletal Muscle". Frontiers in Physiology. 8: 980. doi:10.3389/fphys.2017.00980. PMC 5717538. PMID 29249983.
^ ^a ^b 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. doi:10.1074/jbc.C200269200. PMID 12032137.
^ 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. Bibcode:2003PNAS..100.5040A. doi:10.1073/pnas.0330962100. PMC 154294. PMID 12692302.
^ 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. doi:10.1074/jbc.274.46.32855. PMID 10551848.
^ 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. Bibcode:2001PNAS...9810061A. doi:10.1073/pnas.181348298. PMC 56915. PMID 11526231.

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. doi:10.1007/BF02815182. PMID 9642673.
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. doi:10.1007/BF01534928. PMID 2842876. S2CID 1475105.
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. doi:10.1016/0092-8674(86)90269-2. PMID 2936465. S2CID 43419264.
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. doi:10.1046/j.1365-201X.1996.202000.x. hdl:2066/24180. PMID 8729696.
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. doi:10.1006/geno.1995.1259. PMID 8825625.
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. doi:10.1038/ng1096-191. PMID 8841193. S2CID 22726202.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
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. doi:10.1074/jbc.272.38.23696. PMID 9295312.
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. doi:10.1006/geno.1997.4967. hdl:2066/25426. PMID 9367679. S2CID 41989102.
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 (1 Na/K–ATPase a): 175–85. doi:10.1111/j.1749-6632.1997.tb52249.x. PMID 9405806. S2CID 38068023.
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. doi:10.1074/jbc.273.20.12360. PMID 9575189.
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. doi:10.1074/jbc.274.46.32855. PMID 10551848.
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. doi:10.1007/s004390000297. PMID 10914677. S2CID 31756080.
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. doi:10.1074/jbc.M101229200. PMID 11438520.
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. Bibcode:2001PNAS...9810061A. doi:10.1073/pnas.181348298. PMC 56915. PMID 11526231.
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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Pieske B, Maier LS, Schmidt-Schweda S (2002). "Sarcoplasmic reticulum Ca²⁺ load in human heart failure". Basic Res. Cardiol. 97 Suppl 1 (7): I63–71. doi:10.1007/s003950200032. PMID 12479237. S2CID 22854208.
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. Bibcode:2003PNAS..100..467T. doi:10.1073/pnas.0237326100. PMC 141018. PMID 12525698.

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_olf G_αi GNAI1 GNAI2 GNAI3 Transducin GNAT1 GNAT2 Gustducin GNAT3 G_αq/11 GNAQ GNA11 G_α12/13 GNA12 GNA13
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 superfamily Dynamin Guanylate-binding protein Mitofusin-1 MX1 and MX2 OPA1 Tubulin

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Categories:

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Function

Clinical significance

Interactions

References

External links

Further reading