ORAI3
entrez
93129
canonical
uniprot
Q9BRQ5
canonical
ensembl
ENSG00000175938
resolver
ensp
ENSP00000322249
resolver
enst
ENST00000318663
resolver
genesymbol
ORAI3
resolver
genesymbol_syn
TMEM142C
resolver
hgnc
HGNC:28185
resolver
uniprot
Q96BI8
resolver
uniprot_entry
ORAI3_HUMAN
resolver
uniprot_sec
Q96BI8
resolver
activity_regulation
ACTIVITY REGULATION: CRAC channels are regulated by fast Ca(2+)-dependent inactivation (FCDI), a mechanism that limits Ca(2+) influx and cell toxicity. ORAI3 subunit displays prominent FCDI (PubMed:19706554). Inhibited by lanthanides such as Gd(3+) ions (PubMed:16807233). {ECO:0000269|PubMed:16807233, ECO:0000269|PubMed:19706554}.
uniprot
proteins
amino_acid_sequence
MKGGEGDAGEQAPLNPEGESPAGSATYREFVHRGYLDLMGASQHSLRALSWRRLYLSRAKLKASSRTSALLSGFAMVAMVEVQLESDHEYPPGLLVAFSACTTVLVAVHLFALMVSTCLLPHIEAVSNIHNLNSVHQSPHQRLHRYVELAWGFSTALGTFLFLAEVVLVGWVKFVPIGAPLDTPTPMVPTSRVPGTLAPVATSLSPASNLPRSSASAAPSQAEPACPPRQACGGGGAHGPGWQAAMASTAIMVPVGLVFVAFALHFYRSLVAHKTDRYKQELEELNRLQGELQAV
uniprot
proteins
function
FUNCTION: 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). {ECO:0000269|PubMed:16807233, ECO:0000269|PubMed:17442569, ECO:0000269|PubMed:19182790, ECO:0000269|PubMed:19622606, ECO:0000269|PubMed:19706554, ECO:0000269|PubMed:20354224, ECO:0000269|PubMed:32415068}.
uniprot
proteins
mass_dalton
31499
uniprot
proteins
mutagenesis
MUTAGEN 81; /note="E->Q: Dominant-negative. Inhibits endogenous ARC and CRAC channel currents. Decreases regenerative calcium oscillations."; /evidence="ECO:0000269|PubMed:19622606, ECO:0000269|PubMed:32415068"; MUTAGEN 170; /note="G->C: Causes redox sensitivity with channel activity inhibited by hydrogen peroxide."; /evidence="ECO:0000269|PubMed:20354224"; MUTAGEN 281; /note="E->A: Impairs fast Ca(2+)-dependent inactivation; when associated with A-283 and A-284."; /evidence="ECO:0000269|PubMed:19706554"; MUTAGEN 283; /note="E->A: Impairs fast Ca(2+)-dependent inactivation; when associated with A-281 and A-284."; /evidence="ECO:0000269|PubMed:19706554"; MUTAGEN 284; /note="E->A: Impairs fast Ca(2+)-dependent inactivation; when associated with A-281 and A-283."; /evidence="ECO:0000269|PubMed:19706554
uniprot
proteins
protein_family
Orai family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16582901
uniprot
proteins
pubmed
16807233
uniprot
proteins
pubmed
17442569
uniprot
proteins
pubmed
19182790
uniprot
proteins
pubmed
19622606
uniprot
proteins
pubmed
19706554
uniprot
proteins
pubmed
20354224
uniprot
proteins
pubmed
20418871
uniprot
proteins
pubmed
32415068
uniprot
proteins
pubmed
33941685
uniprot
proteins
sequence_length
295
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16807233}; Multi-pass membrane protein {ECO:0000255}. Note=Colocalizes with STIM1 upon store depletion. {ECO:0000269|PubMed:19706554}.
uniprot
proteins
transmembrane_region
TRANSMEM 63..82; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 95..115; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 157..177; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 244..264; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins