Orai2

Orai2, also known as ORAI2, is a member of the ORAI family of calcium channels that form store-operated calcium entry (SOCE) channels in the plasma membrane. It is encoded by the ORAI2 gene in humans and contributes to the cellular calcium signaling that is triggered when calcium stores in the endoplasmic reticulum are depleted.

Orai2 proteins have the four transmembrane domain architecture characteristic of the ORAI family and can assemble to form hexameric channel complexes. They can function as homomeric channels or form heteromeric channels with other ORAI family members, such as Orai1 or Orai3. The incorporation of Orai2 into these channels can influence properties such as current amplitude, calcium selectivity, and channel kinetics, thereby modulating the overall SOCE response.

Expression of ORAI2 is detected in multiple tissues, including immune cells, brain, muscle, and kidney, with distinct tissue-specific patterns. In immune cells, Orai2 participates in SOCE alongside other ORAI subunits and STIM proteins, contributing to calcium influx that supports activation, cytokine production, and gene transcription. In other tissues, Orai2-mediated calcium entry can play roles in processes such as muscle excitation–contraction coupling and neuronal signaling, although these roles vary by cell type.

Regulation of ORAI2-mediated channels involves interactions with stromal interaction molecule (STIM) proteins, particularly STIM1 and STIM2, which sense ER calcium depletion and trigger channel opening. While ORAI1 has been most strongly linked to essential store-operated currents, ORAI2 modulates the magnitude and kinetics of calcium signals and can influence cellular outcomes when expressed coarsely with other ORAI subunits.

Direct disease associations for ORAI2 mutations are less well established than for ORAI1, but aberrant ORAI2 expression or function can affect calcium signaling and cellular physiology in various contexts.