{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P04191","secondaryAccessions":["P11719"],"uniProtkbId":"AT2A1_RABIT","entryAudit":{"firstPublicDate":"1987-03-20","lastAnnotationUpdateDate":"2026-06-10","lastSequenceUpdateDate":"1987-03-20","entryVersion":210,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Oryctolagus cuniculus","commonName":"Rabbit","taxonId":9986,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Lagomorpha","Leporidae","Oryctolagus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Sarcoplasmic/endoplasmic reticulum calcium ATPase 1"},"shortNames":[{"value":"SERCA1"},{"value":"SR Ca(2+)-ATPase 1"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10914677"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11438520"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15189864"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18075584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23996003"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29081402"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8117720"}],"value":"7.2.2.10"}]},"alternativeNames":[{"fullName":{"value":"Calcium pump 1"}},{"fullName":{"value":"Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform"}},{"fullName":{"value":"Endoplasmic reticulum class 1/2 Ca(2+) ATPase"}}]},"genes":[{"geneName":{"value":"ATP2A1"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8R429"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10914677"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11438520"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15189864"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18075584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23996003"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24270570"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29081402"}],"value":"Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:10914677, PubMed:11438520, PubMed:15189864, PubMed:18075584, PubMed:23996003, PubMed:24270570, PubMed:29081402). Contributes to calcium sequestration involved in muscular excitation/contraction"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Ca(2+)(in) + ATP + H2O = Ca(2+)(out) + ADP + phosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:18105"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:29108"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"7.2.2.10","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10914677"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11438520"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15189864"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18075584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23996003"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29081402"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8117720"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:18106"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"10914677"}]}]},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15192230"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15229613"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15448704"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15618517"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18075584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455424"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8R429"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10551848"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23996003"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29081402"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8428955"}],"value":"Inhibited by sarcolipin (SLN) and myoregulin (MRLN) (PubMed:10551848, PubMed:29081402, PubMed:8428955). Has also been shown to be reversibly inhibited by phospholamban (PLN) at low calcium concentrations in vitro (PubMed:10551848, PubMed:23996003, PubMed:29081402, PubMed:8428955). Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium and this inhibition is regulated by the phosphorylation of PLN in vitro (PubMed:10551848, PubMed:8428955). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O14983"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8R429"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10551848"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455422"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455424"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23996003"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29081402"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8428955"}],"value":"Interacts with sarcolipin (SLN) (PubMed:23455422, PubMed:23455424, PubMed:29081402). Interacts with phospholamban (PLN) (PubMed:10551848, PubMed:23996003, PubMed:29081402, PubMed:8428955). Interacts with myoregulin (MRLN) (By similarity). Interacts with DWORF (By similarity). Interacts with VMP1 (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12585965"}],"value":"Endoplasmic reticulum membrane","id":"SL-0097"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10864315"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12167852"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15192230"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15229613"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15448704"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15618517"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16710301"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18075584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455422"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455424"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23996003"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24270570"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26175901"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28467821"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30482857"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11438520"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15189864"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18075584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455422"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23996003"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29081402"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8117720"}],"value":"Sarcoplasmic reticulum membrane","id":"SL-0241"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10864315"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12167852"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15192230"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15229613"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15448704"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15618517"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16710301"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18075584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455422"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455424"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23996003"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24270570"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26175901"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28467821"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30482857"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"SERCA1B"},"synonyms":[{"value":"Neonatal"}],"isoformIds":["P04191-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"SERCA1A"},"synonyms":[{"value":"Adult"}],"isoformIds":["P04191-2"],"sequenceIds":["VSP_000356"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10864315"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11438520"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15189864"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18075584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455422"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23996003"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29081402"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2936465"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"3029125"}],"value":"Skeletal muscle (at protein level) (PubMed:10864315, PubMed:11438520, PubMed:15189864, PubMed:18075584, PubMed:23455422, PubMed:23996003, PubMed:29081402). Skeletal muscle, fast twitch muscle (type II) fibers (PubMed:2936465, PubMed:3029125)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"3029125"}],"value":"Isoform SERCA1A and isoform SERCA1B are predominantly found in adult and neonatal skeletal muscle respectively"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12167852"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15192230"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15229613"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15448704"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15618517"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16710301"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18075584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455422"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455424"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24270570"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28467821"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30482857"},{"evidenceCode":"ECO:0000305"}],"value":"Ca(2+) and ATP binding cause major rearrangements of the cytoplasmic and transmembrane domains. According to the E1-E2 model, Ca(2+) binding to the cytosolic domain of the pump in the high-affinity E1 conformation is followed by the ATP-dependent phosphorylation of the active site Asp, giving rise to E1P. A conformational change of the phosphoenzyme gives rise to the low-affinity E2P state that exposes the Ca(2+) ions to the lumenal side and promotes Ca(2+) release. Dephosphorylation of the active site Asp mediates the subsequent return to the E1 conformation"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455422"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23455424"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23996003"}],"value":"PLN and SLN both have a single transmembrane helix; both occupy a similar binding site on ATP2A1 that is situated between the ATP2A1 transmembrane helices"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1001,"modifier":"EXACT"}},"description":"Sarcoplasmic/endoplasmic reticulum calcium ATPase 1","featureId":"PRO_0000046189"},{"type":"Topological domain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":48,"modifier":"EXACT"}},"description":"Cytoplasmic","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10864315"}]},{"type":"Transmembrane","location":{"start":{"value":49,"modifier":"EXACT"},"end":{"value":69,"modifier":"EXACT"}},"description":"Helical; Name=1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10864315"}]},{"type":"Topological 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