ORAI3

Pore-forming subunit of two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels (PubMed:16807233, PubMed:17442569, PubMed:19182790, PubMed:19622606, PubMed:19706554, PubMed:20354224, PubMed:32415068). Assembles with ORAI1 and ORAI2 to form hexameric CRAC channels that mediate Ca(2+) influx upon depletion of endoplasmic reticulum Ca(2+) store and channel activation by Ca(2+) sensor STIM1, a process known as store-operated Ca(2+) entry (SOCE). Various pore subunit combinations may account for distinct CRAC channel spatiotemporal and cell-type specific dynamics. ORAI1 mainly contributes to the generation of Ca(2+) plateaus involved in sustained Ca(2+) entry and is dispensable for cytosolic Ca(2+) oscillations, whereas ORAI2 and ORAI3 generate oscillatory patterns. CRAC channels assemble in Ca(2+) signaling microdomains where Ca(2+) influx is coupled to calmodulin and calcineurin signaling and activation of NFAT transcription factors recruited to ORAI1 via AKAP5. CRAC channels are the main pathway for Ca(2+) influx in T cells and promote the immune response to pathogens by activating NFAT-dependent cytokine and chemokine transcription (PubMed:16807233, PubMed:17442569, PubMed:19182790, PubMed:19706554, PubMed:20354224, PubMed:32415068). Assembles with ORAI1 to form channels that mediate store-independent Ca(2+) influx in response to inflammatory metabolites arachidonate or its derivative leukotriene C4, termed ARC and LRC channels respectively (PubMed:19622606, PubMed:32415068).

Belongs to the Orai family.

Expressed in both naive and effector T helper cells with higher levels in effector cells.

• Cell membrane
• Multi-pass membrane protein
• Colocalizes with STIM1 upon store depletion.

TMEM142C, ORAI3, Protein orai-3, Transmembrane protein 142C

• entrezGene:93129
• omim:610930
• swissprot:Q9BRQ5

Proteins

Neuroscience

31499Da