ORAI1
entrez
84876
canonical
uniprot
Q96D31
canonical
ensembl
ENSG00000276045
resolver
ensembl
ENSG00000293604
resolver
genesymbol
ORAI1
resolver
genesymbol_syn
CRACM1
resolver
genesymbol_syn
TMEM142A
resolver
hgnc
HGNC:25896
resolver
uniprot
Q3MHV3
resolver
uniprot
Q6DHX2
resolver
uniprot
Q96BP7
resolver
uniprot
Q96K71
resolver
uniprot_entry
ORAI1_HUMAN
resolver
uniprot_sec
Q3MHV3
resolver
uniprot_sec
Q6DHX2
resolver
uniprot_sec
Q96BP7
resolver
uniprot_sec
Q96K71
resolver
activity_regulation
ACTIVITY REGULATION: Oxidation at Cys-195 leads to inactivation of channel activity (PubMed:20354224, PubMed:28219928). CRAC channels are regulated by fast Ca(2+)-dependent inactivation (FCDI), a mechanism that limits Ca(2+) influx and cell toxicity. Contrary to ORAI2 and ORAI3 subunits, ORAI1 displays small FCDI (PubMed:19706554). Both CRAC and ARC channels are inhibited by lanthanides including La(3+) and Gd(3+) ions (PubMed:16921383, PubMed:19622606, PubMed:26221052, PubMed:32415068). {ECO:0000269|PubMed:16921383, ECO:0000269|PubMed:19622606, ECO:0000269|PubMed:19706554, ECO:0000269|PubMed:20354224, ECO:0000269|PubMed:26221052, ECO:0000269|PubMed:28219928, ECO:0000269|PubMed:32415068}.
uniprot
proteins
amino_acid_sequence
MHPEPAPPPSRSSPELPPSGGSTTSGSRRSRRRSGDGEPPGAPPPPPSAVTYPDWIGQSYSEVMSLNEHSMQALSWRKLYLSRAKLKASSRTSALLSGFAMVAMVEVQLDADHDYPPGLLIAFSACTTVLVAVHLFALMISTCILPNIEAVSNVHNLNSVKESPHERMHRHIELAWAFSTVIGTLLFLAEVVLLCWVKFLPLKKQPGQPRPTSKPPASGAAANVSTSGITPGQAAAIASTTIMVPFGLIFIVFAVHFYRSLVSHKTDRQFQELNELAEFARLQDQLDHRGDHPLTPGSHYA
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency 9 (IMD9) [MIM:612782]: An immune disorder characterized by recurrent infections, impaired activation and proliferative response of T-cells, decreased T-cell production of cytokines, and normal lymphocytes counts and serum immunoglobulin levels. In surviving patients ectodermal dysplasia with anhidrosis and non-progressive myopathy may be observed. {ECO:0000269|PubMed:16147976, ECO:0000269|PubMed:16582901}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myopathy, tubular aggregate, 2 (TAM2) [MIM:615883]: A rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. TAM2 patients have myopathy and pupillary abnormalities. {ECO:0000269|PubMed:24591628, ECO:0000269|PubMed:28058752}. Note=The disease is caused by variants affecting the gene represented in this entry.
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 (Probable) (PubMed:16645049, PubMed:16733527, PubMed:16807233, PubMed:16921383, PubMed:19249086, PubMed:19706554, PubMed:23307288, PubMed:26956484, PubMed:28219928). 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 (PubMed:16582901, PubMed:17442569, PubMed:19182790, PubMed:20354224, PubMed:22641696, PubMed:26221052, PubMed:32415068, PubMed:33941685). 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 (PubMed:19622606, PubMed:32415068). 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 (By similarity) (PubMed:20887894). {ECO:0000250|UniProtKB:Q8BWG9, ECO:0000269|PubMed:16582901, ECO:0000269|PubMed:16645049, ECO:0000269|PubMed:16733527, ECO:0000269|PubMed:16807233, ECO:0000269|PubMed:16921383, ECO:0000269|PubMed:17442569, ECO:0000269|PubMed:19182790, ECO:0000269|PubMed:19249086, ECO:0000269|PubMed:19622606, ECO:0000269|PubMed:19706554, ECO:0000269|PubMed:20354224, ECO:0000269|PubMed:20887894, ECO:0000269|PubMed:22641696, ECO:0000269|PubMed:23307288, ECO:0000269|PubMed:26221052, ECO:0000269|PubMed:26956484, ECO:0000269|PubMed:28219928, ECO:0000269|PubMed:32415068, ECO:0000269|PubMed:33941685, ECO:0000305|PubMed:16766533}.; FUNCTION: [Isoform alpha]: Pore-forming subunit of both CRAC and ARC channels. Couples Ca(2+) influx to NFAT-mediated transcriptional responses. {ECO:0000269|PubMed:16921383, ECO:0000269|PubMed:17442569, ECO:0000269|PubMed:19182790, ECO:0000269|PubMed:19249086, ECO:0000269|PubMed:19622606, ECO:0000269|PubMed:19706554, ECO:0000269|PubMed:22641696, ECO:0000269|PubMed:26221052, ECO:0000269|PubMed:33941685}.; FUNCTION: [Isoform beta]: Pore-forming subunit of CRAC channels exclusively. {ECO:0000269|PubMed:22641696, ECO:0000269|PubMed:26221052, ECO:0000269|PubMed:33941685}.
uniprot
proteins
mass_dalton
32668
uniprot
proteins
mutagenesis
MUTAGEN 3; /note="P->A: Generates both inward and outward rectifying CRAC currents at negative membrane potentials; when associated with A-5. Reduces the activation of CRAC channels by STIM1; when associated with A-5."; /evidence="ECO:0000269|PubMed:19182790"; MUTAGEN 5; /note="P->A: Generates both inward and outward rectifying CRAC currents at negative membrane potentials; when associated with A-3. Reduces the activation of CRAC channels by STIM1; when associated with A-3."; /evidence="ECO:0000269|PubMed:19182790"; MUTAGEN 39; /note="P->A: Generates both inward and outward rectifying CRAC currents at negative membrane potentials; when associated with A-40. Reduces the activation of CRAC channels by STIM1; when associated with A-40."; /evidence="ECO:0000269|PubMed:19182790"; MUTAGEN 40; /note="P->A: Generates both inward and outward rectifying CRAC currents at negative membrane potentials; when associated with A-39. Reduces the activation of CRAC channels by STIM1; when associated with A-39."; /evidence="ECO:0000269|PubMed:19182790"; MUTAGEN 85..87; /note="KLK->ALA: Impairs interaction with CRACR2A/EFCAB4B."; /evidence="ECO:0000269|PubMed:20418871"; MUTAGEN 106; /note="E->A: Has dominant negative effect. Abolishes store-operated Ca(2+) influx. Does not affect localization to the cell membrane."; /evidence="ECO:0000269|PubMed:16921383, ECO:0000269|PubMed:32415068"; MUTAGEN 106; /note="E->D: Markedly decreases store-operated Ca(2+) influx. Increases channel permeability to monovalent cations. Does not affect localization to the cell membrane or STIM1-mediated activation."; /evidence="ECO:0000269|PubMed:16921383, ECO:0000269|PubMed:19182790"; MUTAGEN 106; /note="E->Q: Dominant-negative. Inhibits endogenous CRAC and ARC channels. Confers selective permeability to monovalent cations. Does not affect localization to the cell membrane."; /evidence="ECO:0000269|PubMed:16921383, ECO:0000269|PubMed:17442569, ECO:0000269|PubMed:19622606, ECO:0000269|PubMed:32415068"; MUTAGEN 190; /note="E->A,D: Does not affect store-operated Ca(2+) influx or localization to the cell membrane."; /evidence="ECO:0000269|PubMed:16921383"; MUTAGEN 190; /note="E->Q: Impairs store-operated Ca(2+) influx. Increases channel permeability to monovalent cations. Does not affect localization to the cell membrane."; /evidence="ECO:0000269|PubMed:16921383"; MUTAGEN 195; /note="C->S: Abolishes oxidation and channel inhibition."; /evidence="ECO:0000269|PubMed:20354224, ECO:0000269|PubMed:28219928"; MUTAGEN 223; /note="N->A: Impairs N-glycosylation. Increases channel activity in T cells but does not affect cell surface location."; /evidence="ECO:0000269|PubMed:16921383, ECO:0000269|PubMed:26956484"; MUTAGEN 273; /note="L->S: Strongly reduces the interaction with ATP2C1. Impairs CRAC channel gating by STIM1. Impairs ORAI1 and STIM1 interaction and clustering in punctae."; /evidence="ECO:0000269|PubMed:19182790, ECO:0000269|PubMed:20887894"; MUTAGEN 281; /note="R->A: Strongly reduces calcium current."; /evidence="ECO:0000269|PubMed:24351972"; MUTAGEN 284; /note="D->A: Reduces the maximum current; when associated with A-287 and A-291."; /evidence="ECO:0000269|PubMed:24351972"; MUTAGEN 286; /note="L->S: Strongly reduces calcium current."; /evidence="ECO:0000269|PubMed:24351972"; MUTAGEN 287; /note="D->A: Reduces the maximum current; when associated with A-284 and A-291."; /evidence="ECO:0000269|PubMed:24351972"; MUTAGEN 289; /note="R->A: Strongly reduces calcium current."; /evidence="ECO:0000269|PubMed:24351972"; MUTAGEN 291; /note="D->A: Reduces the maximum current; when associated with A-284 and A-287."; /evidence="ECO:0000269|PubMed:24351972
uniprot
proteins
post_translational_modification
PTM: N-glycosylated (PubMed:16921383, PubMed:19249086, PubMed:26956484). N-glycosylation inhibits channel activity in T cells (PubMed:26956484). {ECO:0000269|PubMed:16921383, ECO:0000269|PubMed:19249086, ECO:0000269|PubMed:26956484}.; PTM: Ubiquitinated. {ECO:0000269|PubMed:23307288}.; PTM: Cys-195 is oxidated, leading to inactivation of channel activity. {ECO:0000269|PubMed:20354224, ECO:0000269|PubMed:28219928}.
uniprot
proteins
protein_family
Orai family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16147976
uniprot
proteins
pubmed
16582901
uniprot
proteins
pubmed
16645049
uniprot
proteins
pubmed
16733527
uniprot
proteins
pubmed
16766533
uniprot
proteins
pubmed
16807233
uniprot
proteins
pubmed
16921383
uniprot
proteins
pubmed
17442569
uniprot
proteins
pubmed
17905723
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19182790
uniprot
proteins
pubmed
19249086
uniprot
proteins
pubmed
19622606
uniprot
proteins
pubmed
19706554
uniprot
proteins
pubmed
20354224
uniprot
proteins
pubmed
20418871
uniprot
proteins
pubmed
20887894
uniprot
proteins
pubmed
22084111
uniprot
proteins
pubmed
22494970
uniprot
proteins
pubmed
22586105
uniprot
proteins
pubmed
22641696
uniprot
proteins
pubmed
23109337
uniprot
proteins
pubmed
23307288
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24351972
uniprot
proteins
pubmed
24591628
uniprot
proteins
pubmed
26221052
uniprot
proteins
pubmed
26956484
uniprot
proteins
pubmed
27185316
uniprot
proteins
pubmed
28058752
uniprot
proteins
pubmed
28219928
uniprot
proteins
pubmed
30481768
uniprot
proteins
pubmed
30573509
uniprot
proteins
pubmed
32415068
uniprot
proteins
pubmed
33941685
uniprot
proteins
sequence_length
301
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16582901, ECO:0000269|PubMed:16645049, ECO:0000269|PubMed:16921383, ECO:0000269|PubMed:19249086, ECO:0000269|PubMed:19706554, ECO:0000269|PubMed:20887894, ECO:0000269|PubMed:23307288, ECO:0000269|PubMed:24351972, ECO:0000269|PubMed:26956484, ECO:0000269|PubMed:27185316, ECO:0000269|PubMed:28058752, ECO:0000269|PubMed:28219928}; Multi-pass membrane protein {ECO:0000269|PubMed:16582901, ECO:0000269|PubMed:16645049, ECO:0000269|PubMed:16921383, ECO:0000269|PubMed:19249086, ECO:0000269|PubMed:22641696, ECO:0000269|PubMed:24351972}. Basolateral cell membrane {ECO:0000250|UniProtKB:Q8BWG9}; Multi-pass membrane protein {ECO:0000269|PubMed:19249086}. Note=Upon store depletion, colocalizes with STIM1 in membrane punctae at ER-PM junctions (PubMed:19182790, PubMed:19249086, PubMed:26221052, PubMed:27185316). {ECO:0000269|PubMed:19182790, ECO:0000269|PubMed:23307288, ECO:0000269|PubMed:26221052, ECO:0000269|PubMed:27185316}.; SUBCELLULAR LOCATION: [Isoform alpha]: Cell membrane {ECO:0000269|PubMed:22641696}.; SUBCELLULAR LOCATION: [Isoform beta]: Cell membrane {ECO:0000269|PubMed:22641696}.
uniprot
proteins
transmembrane_region
TRANSMEM 88..105; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 120..140; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 174..194; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 235..255; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins