{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q8BWG9","secondaryAccessions":["Q8BUD4","Q8R586"],"uniProtkbId":"ORAI1_MOUSE","entryAudit":{"firstPublicDate":"2006-05-16","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2003-03-01","entryVersion":150,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Calcium release-activated calcium channel protein 1"}},"alternativeNames":[{"fullName":{"value":"Protein orai-1"}},{"fullName":{"value":"Transmembrane protein 142A"}}]},"genes":[{"geneName":{"value":"Orai1"},"synonyms":[{"value":"Cracm1"},{"value":"Tmem142a"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23840669"}],"value":"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 (By similarity). Assembles with ORAI2 and ORAI3 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. Activates NFATC2/NFAT1 and NFATC3/NFAT4-mediated transcriptional responses. 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 (By similarity). Assembles with ORAI3 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 (By similarity). Plays a prominent role in Ca(2+) influx at the basolateral membrane of mammary epithelial cells independently of the Ca(2+) content of endoplasmic reticulum or Golgi stores. May mediate transepithelial transport of large quantities of Ca(2+) for milk secretion (PubMed:23840669)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Ca(2+)(in) = Ca(2+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29671"},{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}]},"physiologicalReactions":[{"directionType":"right-to-left","reactionCrossReference":{"database":"Rhea","id":"RHEA:29673"},"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"Oxidation at Cys-197 leads to inactivation of channel activity"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23840669"}],"value":"Oligomerizes in homomeric and heteromeric ORAI complexes. Native CRAC channels most likely consist of hexameric ORAI heteromers, implying that diverse ORAI1, ORAI2 and ORAI3 subunit combinations with distinct biophysical properties can operate in a cell-type specific way. ARC channels are heteropentamers consisting of three ORAI1 and two ORAI3 subunits. Interacts with STIM1 and STIM2; this regulates channel activity. Interacts with CALM; this may displace STIM1 and STIM2 and might thereby modulate channel activity. Interacts (via N-terminus) with AKAP5 upon store depletion. Interacts with CRACR2A/EFCAB4B; the interaction is direct and takes place in absence of Ca(2+). Forms a complex with CRACR2A/EFCAB4B and STIM1 at low concentration of Ca(2+), the complex dissociates at elevated Ca(2+) concentrations. Interacts with ASPH (isoform 8). Interacts with SLC35G1. Interacts with UBQLN1. Interacts with ADCY8; interaction is calcium store depletion independent; interaction occurs in membrane raft; interaction increases markedly after store depletion; positively regulates SOCE-induced adenylate cyclase activity; contributes to the targeting of ADCY8 to discrete regions of the plasma membrane that are shielded from other calcium events. Interacts with EFHB; the interaction takes place upon Ca(2+)-store depletion. Interacts (via N- and C-termini) with ATP2C2 (via N-terminus); this interaction regulates Ca(2+) influx at the plasma membrane (PubMed:23840669). Interacts with TSPAN18; this interaction regulates ORAI1 exit from the endoplasmic (ER), and/or Golgi, and trafficking to the cell surface (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"Colocalizes with STIM1 in membrane punctate structures at ER-PM junctions"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23840669"}],"value":"Basolateral cell membrane","id":"SL-0026"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23840669"}],"value":"Expressed in lactating mammary epithelium (at protein level)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"The Pro-rich region of ORAI1 (residues 3-49) functionally interacts with the polybasic Lys-rich region of STIM1 (residues 672-685) and regulates CRAC channel gating at negative membrane potentials"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"AKAP5 association region (AKAR) mediates coupling of ORAI1 to AKAP5-dependent NFATC2/NFAT1 transcriptional responses"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"N-glycosylated. N-glycosylation inhibits channel activity in T cells"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"Ubiquitinated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"Cys-195 is oxidated, leading to inactivation of channel activity"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the Orai family"}],"commentType":"SIMILARITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96D31"}],"value":"According to a report, ORAI1 has been shown to colocalize with UBQLN1 in the autophagosome as a target for autophagic degradation; ORAI1 is however not an autophagosomal protein"}],"commentType":"CAUTION"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"AAH23149.1","note":"Truncated 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