Calcium release-activated calcium channel protein 3 (ORAI3)

Calcium release-activated calcium channel protein 3 (ORAI3) is a member of the Orai family of transmembrane proteins, which forms highly Ca²⁺-selective channels in the plasma membrane. ORAI3 contributes to store-operated calcium entry (SOCE), responding to ER calcium depletion primarily through STIM1 interaction. It displays unique features distinct from its relatives (Orai1, Orai2), including specialized gating, selectivity, and regulation, and can form heteromeric channels with Orai1. In cardiac tissue, ORAI3 is essential for maintaining sarcomere structure, mitochondrial integrity, and normal cardiac signaling; loss of ORAI3 is linked with severe heart disease. In non-excitable cells, including some cancer cell lines, ORAI3-mediated SOCE is crucial for cell proliferation and survival, implicating it in cancer biology and targeted therapies.

Other names

Orai3Protein orai-3Transmembrane protein 142CTMEM142CMGC13024

Modulation of Ca²⁺ influx via channel inhibition or activation; Alteration of proliferative or apoptotic signaling by regulating calcium entry