Orai calcium release-activated calcium modulator 2 (ORAI2)

Orai calcium release-activated calcium modulator 2 (ORAI2) is a tetraspanning plasma membrane ion channel protein that forms a core component of the calcium release-activated calcium (CRAC) channel, along with related family members ORAI1 and ORAI3[4][3]. ORAI2, often functioning in heteromeric complexes with ORAI1, controls the entry of calcium ions into cells via the process called store-operated calcium entry (SOCE), which is essential for a variety of physiological processes including immune cell activation, gene transcription, and cell survival signaling[2][4]. ORAI2 regulates the magnitude and kinetics of calcium influx, acting as a negative modulator of CRAC channel activity in many cell types by attenuating the calcium current conducted through ORAI1-containing channels[1][4]. In immune cells, especially T cells and neutrophils, ORAI2 is crucial for the fine-tuning of calcium-dependent functions like cytokine production, phagocytosis, and reactive oxygen species generation[2][1][4]. Loss of ORAI2 enhances calcium influx in some immune cells but impairs it in others, indicating context-specific regulation of immune responses and potential implications for immune deficiency, autoimmune diseases, inflammation, infection, and cancer susceptibility[1][2][4][3]. Despite its physiological importance and theoretical attractiveness as an immune modulator, no approved drugs directly target ORAI2 as of 2024, and the predominant focus in pharmacology remains on the more disease-implicated ORAI1. Altering ORAI2 function raises safety concerns such as immunosuppression or autoimmunity due to its central role in immune regulation[1][2][3].

Other names

Protein orai-2C7orf19CBCIP2TMEM142BPP1729FLJ12474FLJ14733H_NH0514P08.8CAP-binding protein complex-interacting protein 2Transmembrane protein 142B

Blockade or modulation of store-operated calcium entry (for molecules affecting ORAI2-containing CRAC channels, not specific to approved drugs)