This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform SERCA2A is involved in the regulation of the contraction/relaxation cycle. May act as a regulator of TNFSF11-mediated Ca(2+) signaling during osteoclastogenesis. ATP + Ca(2+)(in) + H2O = ADP + Ca(2+)(out) + H(+) + phosphate Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (By similarity). Inhibited by sarcolipin (SLN) and myoregulin (MRLN) (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Interacts with sarcolipin (SLN) (By similarity). Interacts with phospholamban (PLN) (By similarity). Interacts with myoregulin (MRLN). Interacts with DWORF (By similarity). Interacts with TMX2. Only isoform 2 is detected in heart, while both isoforms are expressed in brain, with isoform 2 being predominant. 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 that is situated between the ATP2A2 transmembrane helices. Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.