CaATPase

CaATPase refers to calcium transporting ATPases, a family of enzymes that use the energy from ATP hydrolysis to pump Ca2+ across cellular membranes against its electrochemical gradient. They are P-type ATPases and are essential for maintaining low cytosolic Ca2+ concentrations and for refilling Ca2+ stores in organelles such as the sarcoplasmic reticulum, endoplasmic reticulum, and Golgi apparatus.

The main classes are SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase), PMCA (plasma membrane Ca2+-ATPase), and SPCA (secretory pathway Ca2+-ATPase). SERCA pumps Ca2+ from the cytosol into the SR or ER, supporting muscle relaxation and intracellular store replenishment, with isoforms SERCA1–3 in different tissues. PMCA extrudes Ca2+ across the plasma membrane to regulate cytosolic levels, with four main isoforms PMCA1–4 showing tissue distribution. SPCA pumps move Ca2+ (and Mn2+) into the Golgi lumen, contributing to Golgi function and protein processing.

Mechanistically, CaATPases are P-type ATPases that undergo an E1–E2 conformational cycle driven by phosphorylation of a conserved aspartate in the cytosolic domain. Ca2+ binds on one side of the membrane, becomes occluded, and is released on the opposite side as the enzyme returns to its original state, with ATP binding and hydrolysis at the nucleotide-binding domain. Regulation occurs through accessory proteins and signaling pathways: phospholamban inhibits SERCA when dephosphorylated, while other regulators modulate PMCA and SPCA activity as needed.

Physiological roles include muscle contraction and relaxation, neuronal signaling, secretion, and general calcium homeostasis. Disorders arising from CaATPase dysfunction are linked to impaired calcium handling; for example, SERCA1 mutations cause Brody disease, reflecting the importance of CaATPases in diverse tissues.