Self-Cleavage of Human Chloride Channel Accessory 2 Causes a Conformational Shift That Depends on Membrane Anchorage and Is Required for Its Regulation of Store-Operated Calcium Entry.

Human CLCA2 regulates store-operated calcium entry (SOCE) by interacting with Orai1 and STIM1. It is expressed as a 943aa type I transmembrane protein that is cleaved at amino acid 708 to produce a diffusible 100 kDa product. The N-terminal ectodomain contains a hydrolase-like subdomain with a conserved HEXXH zinc-binding motif that is proposed to cleave the precursor autoproteolytically.

Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy.

Intracellular Ca distribution is a tightly regulated process. Numerous Ca chelating, storage, and transport mechanisms are required to maintain normal cellular physiology. Ca-binding proteins, mainly calmodulin and calbindins, sequester free intracellular Ca ions and apportion or transport them to signaling hubs needing the cations.