Calcium ions play a crucial role in the metabolism and physiology of eukaryotes. Calcium exists as a gradient across the plasma membrane, with extracellular concentrations being about 10,000 times higher than intracellular ones. Inside the cell, calcium concentrations can vary between different organelles, the transport of calcium between the cytoplasm and organelles such as the sarcoplasmic and endoplasmic reticulum acting to control cytosolic calcium concentrations. Signalling events often involve an influx of calcium across the plasma membrane, or release of calcium from the sarcoplasmic or endoplasmic reticulum, where the increase in cytosolic calcium can initiate or alter cellular processes. A whole range of cellular processes is regulated by the free cytosolic calcium concentration, ranging from transcription control and cell survival to neurotransmitter release and muscle function. In order for a cell to use calcium as a signalling molecule, the cell must create calcium gradients across membranes. To obtain such concentration differences, calcium ions need to be actively pumped across membranes against a concentration gradient. Cells use calcium pumps to direct the flow of calcium ions through the plasma membrane or organelle membranes, and the resulting gradients are used in a variety of signalling systems mediated by gated ion channels. Calcium pumps are ATPases that transport ions across membranes using energy obtained from the hydrolysis of ATP.
Calcium ATPases are members of the P-type family of ion pumps, which are responsible for the ATP-dependent active transport of ions across a wide variety of cellular membranes. The P-type ATPase family is widespread throughout the phylogenetic tree, and include transporters such as the sodium/potassium pumps and the gastric hydrogen/potassium pumps, and are fundamental in establishing various ion gradients within cells. The designation of P-type comes from the mechanism, which involves the Phosphorylation of an aspartate residue (Asp351) in the active site using the terminal phosphate in ATP, resulting in conformational changes in both the ATP-binding cytoplasmic domains and the calcium-binding transmembrane domain that shuffles the ions across the membrane. The subsequent release of the calcium ions signals the hydrolysis of the aspartyl phosphate group, returning the pump to its original conformation.