ATP2A1
Developmental stage
Isoform SERCA1A and isoform SERCA1B are predominantly found in adult and neonatal skeletal muscle respectively.
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.
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.
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:18075584, PubMed:23996003, PubMed:24270570, PubMed:29081402). Contributes to calcium sequestration involved in muscular excitation/contraction.
Sequence Similarities
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.
Tissue Specificity
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).
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Sarcoplasmic reticulum membrane
- Multi-pass membrane protein
Alternative names
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1, SERCA1, SR Ca(2+)-ATPase 1, Calcium pump 1, Endoplasmic reticulum class 1/2 Ca(2+) ATPase, ATP2A1