ORAI1

ORAI calcium release-activated calcium modulator 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2MAK, 4EHQ
Identifiers
Symbols	ORAI1 ; CRACM1; IMD9; ORAT1; TAM2; TMEM142A
External IDs	OMIM: 610277 MGI: 1925542 HomoloGene: 13117 GeneCards: ORAI1 Gene
Gene ontology Molecular function • protein binding • calmodulin binding • store-operated calcium channel activity • identical protein binding Cellular component • autophagosome • integral component of plasma membrane • membrane • cytoplasmic vesicle • protein complex Biological process • store-operated calcium entry • adaptive immune response • blood coagulation • regulation of calcium ion transport • positive regulation of calcium ion transport • calcium ion transmembrane transport Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	84876	109305
Ensembl	ENSG00000276045	ENSMUSG00000049686
UniProt	Q96D31	Q8BWG9
RefSeq (mRNA)	NM_032790	NM_175423
RefSeq (protein)	NP_116179	NP_780632
Location (UCSC)	Chr 12: 121.63 – 121.64 Mb	Chr 5: 123.02 – 123.03 Mb
PubMed search

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 hexamers.

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][4][5][6]

References

1. 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 (Sep 2009). "Capacitative calcium entry: from concept to molecules". Immunological Reviews 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 (Mar 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.
4. Zhou Y, Meraner P, Kwon HT, Machnes D, Oh-hora M, Zimmer J, Huang Y, Stura A, Rao A, Hogan PG (Jan 2010). "STIM1 gates the store-operated calcium channel ORAI1 in vitro". Nature Structural & Molecular Biology 17 (1): 112–6. doi:10.1038/nsmb.1724. PMC 2902271. PMID 20037597.
5. Gudlur A, Zhou Y, Hogan PG (2013-01-01). "STIM-ORAI interactions that control the CRAC channel". Current Topics in Membranes 71: 33–58. doi:10.1016/b978-0-12-407870-3.00002-0. PMID 23890110.
6. Zhou Y, Srinivasan P, Razavi S, Seymour S, Meraner P, Gudlur A, Stathopulos PB, Ikura M, Rao A, Hogan PG (Aug 2013). "Initial activation of STIM1, the regulator of store-operated calcium entry". Nature Structural & Molecular Biology 20 (8): 973–81. doi:10.1038/nsmb.2625. PMC 3784406. PMID 23851458.