Protein orai-3 (Transmembrane protein 142C)
1_MKGGE 6_ GDAGE 11_ QAPLN 16_ PEGES 21_ PAGSA 26_ TYREF 31_ VHRGY 36_ LDLMG 41_ ASQHS 46_ LRALS 51_ WRRLY 56_ LSRAK 61_ LKASS 66_ RTSAL 71_ LSGFA 76_ MVAMV 81_ EVQLE 86_ SDHEY 91_ PPGLL 96_ VAFSA 101_ CTTVL 106_ VAVHL 111_ FALMV 116_ STCLL 121_ PHIEA 126_ VSNIH 131_ NLNSV 136_ HQSPH 141_ QRLHR 146_ YVELA 151_ WGFST 156_ ALGTF 161_ LFLAE 166_ VVLVG 171_ WVKFV 176_ PIGAP 181_ LDTPT 186_ PMVPT 191_ SRVPG 196_ TLAPV 201_ ATSLS 206_ PASNL 211_ PRSSA 216_ SAAPS 221_ QAEPA 226_ CPPRQ 231_ ACGGG 236_ GAHGP 241_ GWQAA 246_ MASTA 251_ IMVPV 256_ GLVFV 261_ AFALH 266_ FYRSL 271_ VAHKT 276_ DRYKQ 281_ ELEEL 286_NRLQG
1: 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)