Molecular and cellular biology of plasma membrane calcium ATPase.

The plasma membrane calcium ATPase plays an essential role in the ejection of calcium from cells and in the control of its cytosolic concentration. The role of the pump is minor with respect to that of the sodium-calcium exchanger in heart, but is most probably predominant in skeletal and smooth muscle. Biochemical studies combined with molecular biological approaches have led to the elucidation of the primary structure of the pump and have advanced the understanding of its mechanism of action. A spatial model of the pump predicts that ~20% of the protein mass is embedded in the membrane, 80% protrudes into the cytosol, and only a minor portion of the molecule is in contact with the extracellular space. An unexpected complexity has been detected on the genetic level. The human pump is encoded by four independent genes, showing different patterns of tissue-specific expression and alternative splicing of the primary transcripts.