AT2A1_HUMAN
ID AT2A1_HUMAN Reviewed; 1001 AA.
AC O14983; A8K5J9; B3KY17; O14984;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 {ECO:0000305};
DE Short=SERCA1 {ECO:0000305};
DE Short=SR Ca(2+)-ATPase 1;
DE EC=7.2.2.10 {ECO:0000250|UniProtKB:P04191};
DE AltName: Full=Calcium pump 1;
DE AltName: Full=Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform;
DE AltName: Full=Endoplasmic reticulum class 1/2 Ca(2+) ATPase;
GN Name=ATP2A1 {ECO:0000312|HGNC:HGNC:811};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS SERCA1A AND SERCA1B),
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RC TISSUE=Skeletal muscle;
RX PubMed=8825625; DOI=10.1006/geno.1995.1259;
RA Zhang Y., Fujii J., Phillips M.S., Chen H.-S., Karpati G., Yee W.-C.,
RA Schrank B., Cornblath D.R., Boylan K.B., Maclennan D.H.;
RT "Characterization of cDNA and genomic DNA encoding SERCA1, the Ca(2+)-
RT ATPase of human fast-twitch skeletal muscle sarcoplasmic reticulum, and its
RT elimination as a candidate gene for Brody disease.";
RL Genomics 30:415-424(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SERCA1A AND 3).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC TISSUE=Thymus;
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP INTERACTION WITH VMP1.
RX PubMed=28890335; DOI=10.1016/j.molcel.2017.08.005;
RA Zhao Y.G., Chen Y., Miao G., Zhao H., Qu W., Li D., Wang Z., Liu N., Li L.,
RA Chen S., Liu P., Feng D., Zhang H.;
RT "The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity
RT to Control ER-Isolation Membrane Contacts for Autophagosome Formation.";
RL Mol. Cell 67:974.e6-989.e6(2017).
RN [5]
RP VARIANT BROD LEU-789, AND FUNCTION.
RX PubMed=10914677; DOI=10.1007/s004390000297;
RA Odermatt A., Barton K., Khanna V.K., Mathieu J., Escolar D., Kuntzer T.,
RA Karpati G., MacLennan D.H.;
RT "The mutation of Pro(789) to Leu reduces the activity of the fast-twitch
RT skeletal muscle sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA1) and is
RT associated with Brody disease.";
RL Hum. Genet. 106:482-491(2000).
CC -!- FUNCTION: Key regulator of striated muscle performance by acting as the
CC major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+)
CC into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP
CC coupled with the translocation of calcium from the cytosol to the
CC sarcoplasmic reticulum lumen (By similarity). Contributes to calcium
CC sequestration involved in muscular excitation/contraction
CC (PubMed:10914677). {ECO:0000250|UniProtKB:P04191,
CC ECO:0000269|PubMed:10914677}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + Ca(2+)(in) + H2O = ADP + Ca(2+)(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:18105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29108, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216; EC=7.2.2.10;
CC Evidence={ECO:0000250|UniProtKB:P04191};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106;
CC Evidence={ECO:0000250|UniProtKB:P04191};
CC -!- ACTIVITY REGULATION: Inhibited by sarcolipin (SLN), phospholamban (PLN)
CC and myoregulin (MRLN) (By similarity). Reversibly inhibited by
CC phospholamban (PLN) at low calcium concentrations (By similarity).
CC Dephosphorylated PLN decreases the apparent affinity of the ATPase for
CC calcium. This inhibition is regulated by the phosphorylation of PLN (By
CC similarity). Enhanced by DWORF; DWORF increases activity by displacing
CC sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By
CC similarity). {ECO:0000250|UniProtKB:P04191,
CC ECO:0000250|UniProtKB:Q8R429}.
CC -!- SUBUNIT: Interacts with sarcolipin (SLN) (By similarity). Interacts
CC with phospholamban (PLN) (By similarity). Interacts with myoregulin
CC (MRLN). Interacts with DWORF (By similarity). Interacts VMP1
CC (PubMed:28890335). {ECO:0000250|UniProtKB:Q8R429,
CC ECO:0000269|PubMed:28890335}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P04191}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P04191}. Sarcoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P04191}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P04191}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=SERCA1B; Synonyms=ATP2A1B, Neonatal;
CC IsoId=O14983-1; Sequence=Displayed;
CC Name=SERCA1A; Synonyms=ATP2A1A, Adult;
CC IsoId=O14983-2; Sequence=VSP_000355;
CC Name=3;
CC IsoId=O14983-3; Sequence=VSP_054770, VSP_000355;
CC -!- TISSUE SPECIFICITY: Skeletal muscle, fast twitch muscle (type II)
CC fibers. {ECO:0000269|PubMed:8825625}.
CC -!- DEVELOPMENTAL STAGE: Isoform SERCA1A accounts for more than 99% of
CC SERCA1 isoforms expressed in adult skeletal muscle, while isoform
CC SERCA1B predominates in neo-natal skeletal muscle.
CC {ECO:0000269|PubMed:8825625}.
CC -!- INDUCTION: Increased contractile activity leads to a decrease in SERCA1
CC expression, while decreased contractile activity leads to an increase
CC in SERCA1 expression. {ECO:0000269|PubMed:8825625}.
CC -!- DOMAIN: Ca(2+) and ATP binding cause major rearrangements of the
CC cytoplasmic and transmembrane domains. According to the E1-E2 model,
CC Ca(2+) binding to the cytosolic domain of the pump in the high-affinity
CC E1 conformation is followed by the ATP-dependent phosphorylation of the
CC active site Asp, giving rise to E1P. A conformational change of the
CC phosphoenzyme gives rise to the low-affinity E2P state that exposes the
CC Ca(2+) ions to the lumenal side and promotes Ca(2+) release.
CC Dephosphorylation of the active site Asp mediates the subsequent return
CC to the E1 conformation. {ECO:0000250|UniProtKB:P04191}.
CC -!- DOMAIN: PLN and SLN both have a single transmembrane helix; both occupy
CC a similar binding site on ATP2A1 that is situated between the ATP2A1
CC transmembrane helices. {ECO:0000250|UniProtKB:P04191}.
CC -!- DISEASE: Brody disease (BROD) [MIM:601003]: An autosomal recessive
CC muscular disorder characterized by exercise-induced muscle stiffness
CC and cramps primarily affecting the arms, legs, and eyelids, although
CC more generalized muscle involvement may also occur.
CC {ECO:0000269|PubMed:10914677}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IIA subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U96781; AAB53113.1; -; Genomic_DNA.
DR EMBL; U96773; AAB53113.1; JOINED; Genomic_DNA.
DR EMBL; U96774; AAB53113.1; JOINED; Genomic_DNA.
DR EMBL; U96775; AAB53113.1; JOINED; Genomic_DNA.
DR EMBL; U96776; AAB53113.1; JOINED; Genomic_DNA.
DR EMBL; U96777; AAB53113.1; JOINED; Genomic_DNA.
DR EMBL; U96778; AAB53113.1; JOINED; Genomic_DNA.
DR EMBL; U96779; AAB53113.1; JOINED; Genomic_DNA.
DR EMBL; U96780; AAB53113.1; JOINED; Genomic_DNA.
DR EMBL; U96781; AAB53112.1; -; Genomic_DNA.
DR EMBL; U96773; AAB53112.1; JOINED; Genomic_DNA.
DR EMBL; U96774; AAB53112.1; JOINED; Genomic_DNA.
DR EMBL; U96775; AAB53112.1; JOINED; Genomic_DNA.
DR EMBL; U96776; AAB53112.1; JOINED; Genomic_DNA.
DR EMBL; U96777; AAB53112.1; JOINED; Genomic_DNA.
DR EMBL; U96778; AAB53112.1; JOINED; Genomic_DNA.
DR EMBL; U96779; AAB53112.1; JOINED; Genomic_DNA.
DR EMBL; U96780; AAB53112.1; JOINED; Genomic_DNA.
DR EMBL; AK128456; BAG54679.1; -; mRNA.
DR EMBL; AK291314; BAF84003.1; -; mRNA.
DR EMBL; AC109460; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133550; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS10643.1; -. [O14983-1]
DR CCDS; CCDS42139.1; -. [O14983-2]
DR CCDS; CCDS66997.1; -. [O14983-3]
DR RefSeq; NP_001273004.1; NM_001286075.1. [O14983-3]
DR RefSeq; NP_004311.1; NM_004320.4. [O14983-2]
DR RefSeq; NP_775293.1; NM_173201.3. [O14983-1]
DR AlphaFoldDB; O14983; -.
DR SMR; O14983; -.
DR BioGRID; 106977; 503.
DR CORUM; O14983; -.
DR IntAct; O14983; 26.
DR MINT; O14983; -.
DR STRING; 9606.ENSP00000349595; -.
DR BindingDB; O14983; -.
DR ChEMBL; CHEMBL3136; -.
DR DrugBank; DB07604; (6AR,11AS,11BR)-10-ACETYL-9-HYDROXY-7,7-DIMETHYL-2,6,6A,7,11A,11B-HEXAHYDRO-11H-PYRROLO[1',2':2,3]ISOINDOLO[4,5,6-CD]INDOL-11-ONE.
DR DrugBank; DB04638; 2,5-di-tert-butylhydroquinone.
DR DrugBank; DB03909; Adenosine-5'-[Beta, Gamma-Methylene]Triphosphate.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB04444; Tetrafluoroaluminate Ion.
DR GuidetoPHARMACOLOGY; 840; -.
DR iPTMnet; O14983; -.
DR MetOSite; O14983; -.
DR PhosphoSitePlus; O14983; -.
DR SwissPalm; O14983; -.
DR BioMuta; ATP2A1; -.
DR EPD; O14983; -.
DR jPOST; O14983; -.
DR MassIVE; O14983; -.
DR MaxQB; O14983; -.
DR PaxDb; O14983; -.
DR PeptideAtlas; O14983; -.
DR PRIDE; O14983; -.
DR ProteomicsDB; 3827; -.
DR ProteomicsDB; 48358; -. [O14983-1]
DR ProteomicsDB; 48359; -. [O14983-2]
DR Antibodypedia; 26608; 385 antibodies from 36 providers.
DR DNASU; 487; -.
DR Ensembl; ENST00000357084.7; ENSP00000349595.3; ENSG00000196296.14. [O14983-1]
DR Ensembl; ENST00000395503.9; ENSP00000378879.5; ENSG00000196296.14. [O14983-2]
DR Ensembl; ENST00000536376.5; ENSP00000443101.1; ENSG00000196296.14. [O14983-3]
DR GeneID; 487; -.
DR KEGG; hsa:487; -.
DR MANE-Select; ENST00000395503.9; ENSP00000378879.5; NM_004320.6; NP_004311.1. [O14983-2]
DR UCSC; uc002drn.1; human. [O14983-1]
DR CTD; 487; -.
DR DisGeNET; 487; -.
DR GeneCards; ATP2A1; -.
DR HGNC; HGNC:811; ATP2A1.
DR HPA; ENSG00000196296; Group enriched (skeletal muscle, tongue).
DR MalaCards; ATP2A1; -.
DR MIM; 108730; gene.
DR MIM; 601003; phenotype.
DR neXtProt; NX_O14983; -.
DR OpenTargets; ENSG00000196296; -.
DR Orphanet; 53347; Brody myopathy.
DR PharmGKB; PA25105; -.
DR VEuPathDB; HostDB:ENSG00000196296; -.
DR eggNOG; KOG0202; Eukaryota.
DR GeneTree; ENSGT00940000159895; -.
DR HOGENOM; CLU_002360_3_2_1; -.
DR InParanoid; O14983; -.
DR OMA; GRVEVIC; -.
DR PhylomeDB; O14983; -.
DR TreeFam; TF300651; -.
DR PathwayCommons; O14983; -.
DR Reactome; R-HSA-1912420; Pre-NOTCH Processing in Golgi.
DR Reactome; R-HSA-418359; Reduction of cytosolic Ca++ levels.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; O14983; -.
DR SIGNOR; O14983; -.
DR BioGRID-ORCS; 487; 10 hits in 1080 CRISPR screens.
DR ChiTaRS; ATP2A1; human.
DR GeneWiki; ATP2A1; -.
DR GenomeRNAi; 487; -.
DR Pharos; O14983; Tchem.
DR PRO; PR:O14983; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O14983; protein.
DR Bgee; ENSG00000196296; Expressed in hindlimb stylopod muscle and 112 other tissues.
DR ExpressionAtlas; O14983; baseline and differential.
DR Genevisible; O14983; HS.
DR GO; GO:0034704; C:calcium channel complex; IC:BHF-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISS:UniProtKB.
DR GO; GO:0031673; C:H zone; IDA:UniProtKB.
DR GO; GO:0031674; C:I band; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0031095; C:platelet dense tubular network membrane; TAS:Reactome.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0005509; F:calcium ion binding; IMP:UniProtKB.
DR GO; GO:0030899; F:calcium-dependent ATPase activity; ISS:ARUK-UCL.
DR GO; GO:0005388; F:P-type calcium transporter activity; IDA:UniProtKB.
DR GO; GO:0015662; F:P-type ion transporter activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IMP:BHF-UCL.
DR GO; GO:0070509; P:calcium ion import; IMP:BHF-UCL.
DR GO; GO:1990036; P:calcium ion import into sarcoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:BHF-UCL.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0051659; P:maintenance of mitochondrion location; IMP:BHF-UCL.
DR GO; GO:0032471; P:negative regulation of endoplasmic reticulum calcium ion concentration; IMP:BHF-UCL.
DR GO; GO:0045988; P:negative regulation of striated muscle contraction; IMP:UniProtKB.
DR GO; GO:1901896; P:positive regulation of ATPase-coupled calcium transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:1902082; P:positive regulation of calcium ion import into sarcoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0106134; P:positive regulation of cardiac muscle cell contraction; ISS:UniProtKB.
DR GO; GO:0032470; P:positive regulation of endoplasmic reticulum calcium ion concentration; IMP:BHF-UCL.
DR GO; GO:0031448; P:positive regulation of fast-twitch skeletal muscle fiber contraction; IDA:UniProtKB.
DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; IMP:BHF-UCL.
DR GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome.
DR GO; GO:0006942; P:regulation of striated muscle contraction; IMP:UniProtKB.
DR GO; GO:0090076; P:relaxation of skeletal muscle; IDA:BHF-UCL.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:BHF-UCL.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C.
DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR005782; P-type_ATPase_IIA.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR PRINTS; PR00120; HATPASE.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01116; ATPase-IIA1_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Calcium; Calcium transport;
KW Disease variant; Disulfide bond; Endoplasmic reticulum; Ion transport;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Sarcoplasmic reticulum; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1001
FT /note="Sarcoplasmic/endoplasmic reticulum calcium ATPase 1"
FT /id="PRO_0000046187"
FT TRANSMEM 49..69
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT TRANSMEM 90..110
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT TRANSMEM 254..273
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT TRANSMEM 296..313
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT TRANSMEM 758..777
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT TRANSMEM 788..808
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT TRANSMEM 829..851
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT TRANSMEM 898..917
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT TRANSMEM 931..949
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT TRANSMEM 965..985
FT /note="Helical; Name=10"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT REGION 788..808
FT /note="Interaction with PLN"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT REGION 932..943
FT /note="Interaction with PLN"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT ACT_SITE 351
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 304
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 305
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 307
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 309
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 351
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 353
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 353
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 442
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 489
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 515
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 560
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 625..627
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 678
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 684
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 703
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 706
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 768
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 771
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 796
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 799
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 800
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 800
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 908
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT MOD_RES 441
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q64578"
FT MOD_RES 569
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q64578"
FT MOD_RES 581
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64578"
FT DISULFID 876..888
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT VAR_SEQ 1..125
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054770"
FT VAR_SEQ 994..1001
FT /note="DPEDERRK -> G (in isoform SERCA1A and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:8825625"
FT /id="VSP_000355"
FT VARIANT 789
FT /note="P -> L (in BROD; dbSNP:rs121918115)"
FT /evidence="ECO:0000269|PubMed:10914677"
FT /id="VAR_015588"
SQ SEQUENCE 1001 AA; 110252 MW; C8F33809B56FDDEE CRC64;
MEAAHAKTTE ECLAYFGVSE TTGLTPDQVK RNLEKYGLNE LPAEEGKTLW ELVIEQFEDL
LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILIA NAIVGVWQER NAENAIEALK
EYEPEMGKVY RADRKSVQRI KARDIVPGDI VEVAVGDKVP ADIRILAIKS TTLRVDQSIL
TGESVSVIKH TEPVPDPRAV NQDKKNMLFS GTNIAAGKAL GIVATTGVGT EIGKIRDQMA
ATEQDKTPLQ QKLDEFGEQL SKVISLICVA VWLINIGHFN DPVHGGSWFR GAIYYFKIAV
ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ
MSVCKMFIID KVDGDICLLN EFSITGSTYA PEGEVLKNDK PVRPGQYDGL VELATICALC
NDSSLDFNEA KGVYEKVGEA TETALTTLVE KMNVFNTDVR SLSKVERANA CNSVIRQLMK
KEFTLEFSRD RKSMSVYCSP AKSSRAAVGN KMFVKGAPEG VIDRCNYVRV GTTRVPLTGP
VKEKIMAVIK EWGTGRDTLR CLALATRDTP PKREEMVLDD SARFLEYETD LTFVGVVGML
DPPRKEVTGS IQLCRDAGIR VIMITGDNKG TAIAICRRIG IFGENEEVAD RAYTGREFDD
LPLAEQREAC RRACCFARVE PSHKSKIVEY LQSYDEITAM TGDGVNDAPA LKKAEIGIAM
GSGTAVAKTA SEMVLADDNF STIVAAVEEG RAIYNNMKQF IRYLISSNVG EVVCIFLTAA
LGLPEALIPV QLLWVNLVTD GLPATALGFN PPDLDIMDRP PRSPKEPLIS GWLFFRYMAI
GGYVGAATVG AAAWWFLYAE DGPHVNYSQL THFMQCTEDN THFEGIDCEV FEAPEPMTMA
LSVLVTIEMC NALNSLSENQ SLLRMPPWVN IWLLGSICLS MSLHFLILYV DPLPMIFKLR
ALDLTQWLMV LKISLPVIGL DEILKFVARN YLEDPEDERR K
