Calcium-transporting ATPase (Ca2+-ATPase) (Ca2+-ATPase)

Calcium-transporting ATPases are a vital group of P-type ATPases that maintain low resting cytosolic calcium levels by actively pumping calcium ions into organelles or out of the cell against a concentration gradient [PubMed: 23536154]. This family primarily includes the Sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), the Plasma membrane calcium ATPase (PMCA), and the Secretory pathway calcium ATPase (SPCA) [UniProt: P16615]. These enzymes are fundamental to physiological processes such as muscle relaxation, where SERCA2a sequesters calcium to end contraction, and signal transduction, where PMCA regulates the duration of calcium signals [PubMed: 30243718]. Dysregulation of these pumps is linked to several major diseases; for instance, impaired SERCA2a function is a primary driver of heart failure, while mutations in ATP2A2 (SERCA2) and ATP2C1 (SPCA1) cause the skin disorders Darier disease and Hailey-Hailey disease, respectively [StatPearls: NBK545136]. Pharmacological modulation of these ATPases is a significant area of drug development, with SERCA activators like istaroxime being investigated for heart failure and SERCA inhibitors like mipsagargin being evaluated for their ability to induce apoptosis in cancer cells [ClinicalTrials.gov: NCT00523484]. However, targeting these pumps requires high isoform specificity to avoid systemic toxicity and unintended effects on global calcium signaling [PubMed: 27103504].

Other names

SERCAPMCASPCASarcoplasmic/endoplasmic reticulum calcium ATPasePlasma membrane calcium ATPaseSecretory pathway calcium ATPaseCa2+-pumping ATPaseCalcium pumpATP2AATP2BATP2C

Calcium-transporting ATPases utilize the energy from ATP hydrolysis to transport calcium ions across cellular membranes against their electrochemical gradient, thereby maintaining low cytosolic calcium levels; drugs targeting these enzymes either activate the pump to improve calcium sequestration (e.g., in heart failure) or inhibit it to trigger calcium-dependent apoptosis (e.g., in cancer) [PubMed: 30243718, 27103504].