UniProt functional annotation for P04191



	UniProt functional annotation for P04191

UniProt codes: P04191, P11719.

Organism: Oryctolagus cuniculus (Rabbit).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.

Function: 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:29081402, PubMed:18075584, PubMed:24270570, PubMed:23996003). Contributes to calcium sequestration involved in muscular excitation/contraction. {ECO:0000250|UniProtKB:Q8R429, ECO:0000269|PubMed:10914677, ECO:0000269|PubMed:11438520, ECO:0000269|PubMed:15189864, ECO:0000269|PubMed:18075584, ECO:0000269|PubMed:23996003, ECO:0000269|PubMed:24270570, ECO:0000269|PubMed:29081402}.

Catalytic activity: Reaction=ATP + Ca(2+)(in) + H2O = ADP + Ca(2+)(out) + H(+) + phosphate; Xref=Rhea:RHEA:18105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29108, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=7.2.2.10; Evidence={ECO:0000269|PubMed:10914677, ECO:0000269|PubMed:11438520, ECO:0000269|PubMed:15189864, ECO:0000269|PubMed:18075584, ECO:0000269|PubMed:23996003, ECO:0000269|PubMed:29081402, ECO:0000269|PubMed:8117720}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106; Evidence={ECO:0000305|PubMed:10914677};

Activity regulation: Inhibited by sarcolipin (SLN) and myoregulin (MRLN) (PubMed:10551848, PubMed:8428955, PubMed:29081402). Inhibited by phospholamban (PLN) (PubMed:10551848, PubMed:8428955, PubMed:29081402, PubMed:23996003). Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (PubMed:10551848, PubMed:8428955, PubMed:29081402, PubMed:23996003). Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium (PubMed:10551848, PubMed:8428955). This inhibition is regulated by the phosphorylation of PLN (PubMed:10551848, PubMed:8428955). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). {ECO:0000250|UniProtKB:Q8R429, ECO:0000269|PubMed:10551848, ECO:0000269|PubMed:23996003, ECO:0000269|PubMed:29081402, ECO:0000269|PubMed:8428955}.

Subunit: Interacts with sarcolipin (SLN) (PubMed:29081402, PubMed:23455422, PubMed:23455424). Interacts with phospholamban (PLN) (PubMed:8428955, PubMed:10551848, PubMed:29081402, PubMed:23996003). Interacts with myoregulin (MRLN) (By similarity). Interacts with DWORF (By similarity). Interacts VMP1 (By similarity). {ECO:0000250|UniProtKB:O14983, ECO:0000250|UniProtKB:Q8R429, ECO:0000269|PubMed:10551848, ECO:0000269|PubMed:23455422, ECO:0000269|PubMed:23455424, ECO:0000269|PubMed:23996003, ECO:0000269|PubMed:29081402, ECO:0000269|PubMed:8428955}.

Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:12585965}; Multi-pass membrane protein {ECO:0000269|PubMed:10864315, ECO:0000269|PubMed:12167852, ECO:0000269|PubMed:15192230, ECO:0000269|PubMed:15229613, ECO:0000269|PubMed:15448704, ECO:0000269|PubMed:15618517, ECO:0000269|PubMed:16710301, ECO:0000269|PubMed:18075584, ECO:0000269|PubMed:23455422, ECO:0000269|PubMed:23455424, ECO:0000269|PubMed:23996003, ECO:0000269|PubMed:24270570, ECO:0000269|PubMed:26175901, ECO:0000269|PubMed:28467821, ECO:0000269|PubMed:30482857}. Sarcoplasmic reticulum membrane {ECO:0000269|PubMed:11438520, ECO:0000269|PubMed:15189864, ECO:0000269|PubMed:18075584, ECO:0000269|PubMed:23455422, ECO:0000269|PubMed:23996003, ECO:0000269|PubMed:29081402, ECO:0000269|PubMed:8117720}; Multi-pass membrane protein {ECO:0000269|PubMed:10864315, ECO:0000269|PubMed:12167852, ECO:0000269|PubMed:15192230, ECO:0000269|PubMed:15229613, ECO:0000269|PubMed:15448704, ECO:0000269|PubMed:15618517, ECO:0000269|PubMed:16710301, ECO:0000269|PubMed:18075584, ECO:0000269|PubMed:23455422, ECO:0000269|PubMed:23455424, ECO:0000269|PubMed:23996003, ECO:0000269|PubMed:24270570, ECO:0000269|PubMed:26175901, ECO:0000269|PubMed:28467821, ECO:0000269|PubMed:30482857}.

Tissue specificity: Skeletal muscle (at protein level) (PubMed:11438520, PubMed:15189864, PubMed:29081402, PubMed:10864315, PubMed:18075584, PubMed:23996003, PubMed:23455422). Skeletal muscle, fast twitch muscle (type II) fibers (PubMed:2936465, PubMed:3029125). {ECO:0000269|PubMed:10864315, ECO:0000269|PubMed:11438520, ECO:0000269|PubMed:15189864, ECO:0000269|PubMed:18075584, ECO:0000269|PubMed:23455422, ECO:0000269|PubMed:23996003, ECO:0000269|PubMed:29081402, ECO:0000269|PubMed:2936465, ECO:0000269|PubMed:3029125}.

Developmental stage: Isoform SERCA1A and isoform SERCA1B are predominantly found in adult and neonatal skeletal muscle respectively. {ECO:0000269|PubMed:3029125}.

Domain: 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. {ECO:0000269|PubMed:12167852, ECO:0000269|PubMed:15192230, ECO:0000269|PubMed:15229613, ECO:0000269|PubMed:15448704, ECO:0000269|PubMed:15618517, ECO:0000269|PubMed:16710301, ECO:0000269|PubMed:18075584, ECO:0000269|PubMed:23455422, ECO:0000269|PubMed:23455424, ECO:0000269|PubMed:24270570, ECO:0000269|PubMed:28467821, ECO:0000269|PubMed:30482857, ECO:0000305}.

Domain: 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. {ECO:0000269|PubMed:23455422, ECO:0000269|PubMed:23455424, ECO:0000269|PubMed:23996003}.

Similarity: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Oryctolagus cuniculus (Rabbit).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.



Function:		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:29081402, PubMed:18075584, PubMed:24270570, PubMed:23996003). Contributes to calcium sequestration involved in muscular excitation/contraction. {ECO:0000250\|UniProtKB:Q8R429, ECO:0000269\|PubMed:10914677, ECO:0000269\|PubMed:11438520, ECO:0000269\|PubMed:15189864, ECO:0000269\|PubMed:18075584, ECO:0000269\|PubMed:23996003, ECO:0000269\|PubMed:24270570, ECO:0000269\|PubMed:29081402}.


Catalytic activity:		Reaction=ATP + Ca(2+)(in) + H2O = ADP + Ca(2+)(out) + H(+) + phosphate; Xref=Rhea:RHEA:18105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29108, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=7.2.2.10; Evidence={ECO:0000269\|PubMed:10914677, ECO:0000269\|PubMed:11438520, ECO:0000269\|PubMed:15189864, ECO:0000269\|PubMed:18075584, ECO:0000269\|PubMed:23996003, ECO:0000269\|PubMed:29081402, ECO:0000269\|PubMed:8117720}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106; Evidence={ECO:0000305\|PubMed:10914677};
Activity regulation:		Inhibited by sarcolipin (SLN) and myoregulin (MRLN) (PubMed:10551848, PubMed:8428955, PubMed:29081402). Inhibited by phospholamban (PLN) (PubMed:10551848, PubMed:8428955, PubMed:29081402, PubMed:23996003). Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (PubMed:10551848, PubMed:8428955, PubMed:29081402, PubMed:23996003). Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium (PubMed:10551848, PubMed:8428955). This inhibition is regulated by the phosphorylation of PLN (PubMed:10551848, PubMed:8428955). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). {ECO:0000250\|UniProtKB:Q8R429, ECO:0000269\|PubMed:10551848, ECO:0000269\|PubMed:23996003, ECO:0000269\|PubMed:29081402, ECO:0000269\|PubMed:8428955}.
Subunit:		Interacts with sarcolipin (SLN) (PubMed:29081402, PubMed:23455422, PubMed:23455424). Interacts with phospholamban (PLN) (PubMed:8428955, PubMed:10551848, PubMed:29081402, PubMed:23996003). Interacts with myoregulin (MRLN) (By similarity). Interacts with DWORF (By similarity). Interacts VMP1 (By similarity). {ECO:0000250\|UniProtKB:O14983, ECO:0000250\|UniProtKB:Q8R429, ECO:0000269\|PubMed:10551848, ECO:0000269\|PubMed:23455422, ECO:0000269\|PubMed:23455424, ECO:0000269\|PubMed:23996003, ECO:0000269\|PubMed:29081402, ECO:0000269\|PubMed:8428955}.
Subcellular location:		Endoplasmic reticulum membrane {ECO:0000269\|PubMed:12585965}; Multi-pass membrane protein {ECO:0000269\|PubMed:10864315, ECO:0000269\|PubMed:12167852, ECO:0000269\|PubMed:15192230, ECO:0000269\|PubMed:15229613, ECO:0000269\|PubMed:15448704, ECO:0000269\|PubMed:15618517, ECO:0000269\|PubMed:16710301, ECO:0000269\|PubMed:18075584, ECO:0000269\|PubMed:23455422, ECO:0000269\|PubMed:23455424, ECO:0000269\|PubMed:23996003, ECO:0000269\|PubMed:24270570, ECO:0000269\|PubMed:26175901, ECO:0000269\|PubMed:28467821, ECO:0000269\|PubMed:30482857}. Sarcoplasmic reticulum membrane {ECO:0000269\|PubMed:11438520, ECO:0000269\|PubMed:15189864, ECO:0000269\|PubMed:18075584, ECO:0000269\|PubMed:23455422, ECO:0000269\|PubMed:23996003, ECO:0000269\|PubMed:29081402, ECO:0000269\|PubMed:8117720}; Multi-pass membrane protein {ECO:0000269\|PubMed:10864315, ECO:0000269\|PubMed:12167852, ECO:0000269\|PubMed:15192230, ECO:0000269\|PubMed:15229613, ECO:0000269\|PubMed:15448704, ECO:0000269\|PubMed:15618517, ECO:0000269\|PubMed:16710301, ECO:0000269\|PubMed:18075584, ECO:0000269\|PubMed:23455422, ECO:0000269\|PubMed:23455424, ECO:0000269\|PubMed:23996003, ECO:0000269\|PubMed:24270570, ECO:0000269\|PubMed:26175901, ECO:0000269\|PubMed:28467821, ECO:0000269\|PubMed:30482857}.
Tissue specificity:		Skeletal muscle (at protein level) (PubMed:11438520, PubMed:15189864, PubMed:29081402, PubMed:10864315, PubMed:18075584, PubMed:23996003, PubMed:23455422). Skeletal muscle, fast twitch muscle (type II) fibers (PubMed:2936465, PubMed:3029125). {ECO:0000269\|PubMed:10864315, ECO:0000269\|PubMed:11438520, ECO:0000269\|PubMed:15189864, ECO:0000269\|PubMed:18075584, ECO:0000269\|PubMed:23455422, ECO:0000269\|PubMed:23996003, ECO:0000269\|PubMed:29081402, ECO:0000269\|PubMed:2936465, ECO:0000269\|PubMed:3029125}.
Developmental stage:		Isoform SERCA1A and isoform SERCA1B are predominantly found in adult and neonatal skeletal muscle respectively. {ECO:0000269\|PubMed:3029125}.
Domain:		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. {ECO:0000269\|PubMed:12167852, ECO:0000269\|PubMed:15192230, ECO:0000269\|PubMed:15229613, ECO:0000269\|PubMed:15448704, ECO:0000269\|PubMed:15618517, ECO:0000269\|PubMed:16710301, ECO:0000269\|PubMed:18075584, ECO:0000269\|PubMed:23455422, ECO:0000269\|PubMed:23455424, ECO:0000269\|PubMed:24270570, ECO:0000269\|PubMed:28467821, ECO:0000269\|PubMed:30482857, ECO:0000305}.
Domain:		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. {ECO:0000269\|PubMed:23455422, ECO:0000269\|PubMed:23455424, ECO:0000269\|PubMed:23996003}.
Similarity:		Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily. {ECO:0000305}.