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Beschreibung

Plasma membrane calcium-transporting ATPase (isoforms 1-4) UniProt: P20020, Q01814, Q16720, P23634, also known as PMCA, Plasma membrane calcium pump) is encoded by the ATP2B1, ATP2B2, ATP2B3, ATP2B4 genes (Gene ID: 490, 491, 492, 493) in human. PMCAs are multi-pass membrane proteins that act as a calcium/calmodulin-regulated and magnesium-dependent enzymes and catalyze the hydrolysis of ATP coupled with the transport of calcium out of the cell. PMCAs serve as the main off switch for calcium signals in all types of cells. Although there are four separate genes that code for PMCAs 1-4, alternative splicing of the primary transcripts further increases the number of PMCA variants to about 20, which differ significantly in their regulatory and kinetic properties. PMCA activity is shown to be regulated at (a) the transcriptional level (b) by calmodulin binding and (c) by their subcellular localization. The localization of different PMCAs is regulated in various complex, cell type-specific ways. PMCA1 is ubiquitously expressed, PMCA2 is mainly expressed in brain cortex, but lower levels are also found in skeletal muscle, heart muscle, stomach, liver, kidney and lung. PMCA3 is highly expressed in the cerebellum, particularly in the presynaptic terminals of parallel fibers-Purkinje neurons. PMCA4 is expressed ubiquitously, however, its tissue distribution varies with its isoforms. (Ref.: Antalffy, G et al. (2013). Biochim. Biophys. Acta 1833(12), 2561-2572, Strehler, EE (2015). Biochem. Biophys. Commun. 460 (1), 26-33)