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ORAI calcium release-activated calcium modulator 1
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols ORAI1 ; CRACM1; IMD9; ORAT1; TAM2; TMEM142A
External IDs OMIM610277 MGI1925542 HomoloGene13117 GeneCards: ORAI1 Gene
Species Human Mouse
Entrez 84876 109305
Ensembl ENSG00000182500 ENSMUSG00000049686
UniProt Q96D31 Q8BWG9
RefSeq (mRNA) NM_032790 NM_175423
RefSeq (protein) NP_116179 NP_780632
Location (UCSC) Chr 12:
122.06 – 122.08 Mb
Chr 5:
123.02 – 123.03 Mb
PubMed search [1] [2]

Calcium release-activated calcium channel protein 1 is a calcium selective ion channel that in humans is encoded by the ORAI1 gene.[1] Orai channels play an important role in the activation of T-lymphocytes. The loss of function mutation of Orai1 causes severe combined immunodeficiency (SCID) in humans[1] The mammalian orai family has two additional homologs, orai2 and orai3. Orai proteins share no homology with any other ion channel family of any other known proteins. They have 4 transmembrane domains and form tetramers.

Orai channels are activated upon the depletion of internal calcium stores, which is called the "store-operated" or the "capacitative" mechanism.[2] They are molecular constituents of the "calcium release activated calcium currents" (ICRAC). Upon activation of phospholipase C by various cell surface receptors, inositol trisphosphate is formed that releases calcium from the endoplasmic reticulum. The decreased calcium concentration in the endoplasmic reticulum is sensed by the STIM1 protein. STIM1 clusters upon the depletion of the calcium stores and forms "puncta", and relocates near the plasma membrane, where it activates orai1 via protein protein interaction.[3]


  1. ^ a b Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A (May 2006). "A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function". Nature 441 (7090): 179–85. doi:10.1038/nature04702. PMID 16582901. 
  2. ^ Putney JW (2009). "Capacitative calcium entry: from concept to molecules.". Immunol Rev 231 (1): 10–22. doi:10.1111/j.1600-065X.2009.00810.x. PMID 19754887. 
  3. ^ Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED, Raunser S, Walz T, Garcia KC, Dolmetsch RE, Lewis RS. (2009). "STIM1 Clusters and Activates CRAC Channels via Direct Binding of a Cytosolic Domain to Orai1". Cell 136 (5): 876–90. doi:10.1016/j.cell.2009.02.014. PMC 2670439. PMID 19249086.