The sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA) is an intracellular membrane-associated pump for sequestering calcium from the cytosol into intracellular organelles, usually associated with the recovery phase following excitation of muscle and nerves.

The plasma membrane Ca²⁺-ATPase (PMCA) is a cell-surface pump for extruding calcium from the cytosol, usually associated with the recovery phase following excitation of cells. The active pump is a homodimer, each subunit of which is made up of ten TM segments, with cytosolic C- and N-termini and two large intracellular loops.

Secretory pathway Ca²⁺-ATPases (SPCA) allow accumulation of calcium and manganese in the Golgi apparatus.

The fungal toxin ochratoxin A has been described to activate SERCA in kidney microsomes [1]. Cyclopiazonic acid [4], thapsigargin [3] and BHQ are widely employed to block SERCA. Thapsigargin has also been described to block the TRPV1 vanilloid receptor [7].

The stoichiometry of flux through the PMCA differs from SERCA, with the PMCA transporting 1 Ca²⁺ while SERCA transports 2 Ca²⁺.

Loss-of-function mutations in SPCA1 appear to underlie Hailey-Hailey disease [2].

1. Chong X, Rahimtula AD. (1992) Alterations in ATP-dependent calcium uptake by rat renal cortex microsomes following ochratoxin A administration in vivo or addition in vitro. Biochem Pharmacol, 44 (7): 1401-9. [PMID:1417961]

2. Hu Z, Bonifas JM, Beech J, Bench G, Shigihara T, Ogawa H, Ikeda S, Mauro T, Epstein EH. (2000) Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Nat Genet, 24 (1): 61-5. [PMID:10615129]

3. Lytton J, Westlin M, Hanley MR. (1991) Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps. J Biol Chem, 266 (26): 17067-71. [PMID:1832668]

4. Seidler NW, Jona I, Vegh M, Martonosi A. (1989) Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum. J Biol Chem, 264 (30): 17816-23. [PMID:2530215]

5. Singh P, Mhaka AM, Christensen SB, Gray JJ, Denmeade SR, Isaacs JT. (2005) Applying linear interaction energy method for rational design of noncompetitive allosteric inhibitors of the sarco- and endoplasmic reticulum calcium-ATPase. J Med Chem, 48 (8): 3005-14. [PMID:15828839]

6. Sordi G, Goti A, Young HS, Palchetti I, Tadini-Buoninsegni F. (2021) Stimulation of Ca²⁺ -ATPase Transport Activity by a Small-Molecule Drug. ChemMedChem, 16 (21): 3293-3299. [PMID:34297466]

7. Tóth A, Kedei N, Szabó T, Wang Y, Blumberg PM. (2002) Thapsigargin binds to and inhibits the cloned vanilloid receptor-1. Biochem Biophys Res Commun, 293 (2): 777-82. [PMID:12054538]