Plasma membrane calcium transporting ATPase isoform 2

Plasma membrane calcium ATPase isoform 2 (PMCA2) is one of four mammalian isoforms of the PMCA family. The PMCAs are calcium-transporting P-type ATPases responsible for the extrusion of ionized calcium (Ca²⁺) from the cytosol to the extracellular milieu. The PMCAs form an obligatory aspartyl-phosphate intermediate during the reaction cycle (hence their classification as P-type ATPases). These pumps are responsible for the resetting and maintenance of resting levels of intracellular free Ca²⁺ and may be involved in local and dynamic regulation of Ca²⁺ signaling in diverse tissues and cell types. The PMCAs generally exhibit low activity at low (50 nM) Ca²⁺ concentrations and are activated by interaction with Ca²⁺-calmodulin. PMCA2 has a high basal activity and is one of the fastest pumps with respect to Ca²⁺-calmodulin activation. PMCA2 is most highly expressed in the brain, where, for example, it is crucial for sensory neuron function in the inner ear. Some alternative splice variants of PMCA2 interact with PDZ domain-containing proteins to form multi-protein calcium signaling complexes anchored to the membrane cytoskeleton. Ser/Thr phosphorylation of PMCA2 has been reported to regulate pump activity in a complex manner.