ORAI3, also known as Transmembrane protein 142C (TMEM142C), is a 31.5kD multi-pass membrane protein belonging to the ORAI family. Antigen stimulation of immune cells triggers Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC) channels. CRAC channels are the main pathway for Ca2+ influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT. ORAI3 is one of two mammalian homologs of ORAI1, a four- transmembrane spanning protein that is an essential component of CRAC channels. ORAI3, along with ORAI1 and ORAI2, functions as a Ca2+ plasma membrane channel that is gated through interactions with STIM1, the store-activated endoplasmic reticulum Ca2+ sensor. Studies indicate that ORAI3 channels undergo a lesser degree of depotentiation than ORAI1 or ORAI2.
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