NameCalcium release-activated calcium channel protein 1
Synonyms
  • CRACM1
  • Protein orai-1
  • TMEM142A
  • Transmembrane protein 142A
Gene NameORAI1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008867|Calcium release-activated calcium channel protein 1
MHPEPAPPPSRSSPELPPSGGSTTSGSRRSRRRSGDGEPPGAPPPPPSAVTYPDWIGQSY
SEVMSLNEHSMQALSWRKLYLSRAKLKASSRTSALLSGFAMVAMVEVQLDADHDYPPGLL
IAFSACTTVLVAVHLFALMISTCILPNIEAVSNVHNLNSVKESPHERMHRHIELAWAFST
VIGTLLFLAEVVLLCWVKFLPLKKQPGQPRPTSKPPASGAAANVSTSGITPGQAAAIAST
TIMVPFGLIFIVFAVHFYRSLVSHKTDRQFQELNELAEFARLQDQLDHRGDHPLTPGSHY
A
Number of residues301
Molecular Weight32668.1
Theoretical pINot Available
GO Classification
Functions
  • identical protein binding
  • store-operated calcium channel activity
Processes
  • blood coagulation
  • regulation of calcium ion transport
  • adaptive immune response
  • positive regulation of calcium ion transport
  • store-operated calcium entry
Components
  • cytoplasmic vesicle
  • integral component of plasma membrane
  • autophagosome
  • membrane
  • protein complex
General FunctionStore-operated calcium channel activity
Specific FunctionCa(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores and channel activation by the Ca(2+) sensor, STIM1 (PubMed:16582901, PubMed:16645049, PubMed:16733527, PubMed:16766533, PubMed:16807233, PubMed:19249086, PubMed:23307288, PubMed:24351972, PubMed:24591628). CRAC channels are the main pathway for Ca(2+) influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT (PubMed:16582901).
Pfam Domain Function
Transmembrane Regions88-105 120-140 174-194 235-255
GenBank Protein IDNot Available
UniProtKB IDQ96D31
UniProtKB Entry NameCRCM1_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0013463|Calcium release-activated calcium channel protein 1 (ORAI1)
ATGCATCCGGAGCCCGCCCCGCCCCCGAGCCGCAGCAGTCCCGAGCTTCCCCCAAGCGGC
GGCAGCACCACCAGCGGCAGCCGCCGGAGCCGCCGCCGCAGCGGGGACGGGGAGCCCCCG
GGGGCCCCGCCACCGCCGCCGTCCGCCGTCACCTACCCGGACTGGATCGGCCAGAGTTAC
TCCGAGGTGATGAGCCTCAACGAGCACTCCATGCAGGCGCTGTCCTGGCGCAAGCTCTAC
TTGAGCCGCGCCAAGCTTAAAGCCTCCAGCCGGACCTCGGCTCTGCTCTCCGGCTTCGCC
ATGGTGGCAATGGTGGAGGTGCAGCTGGACGCTGACCACGACTACCCACCGGGGCTGCTC
ATCGCCTTCAGTGCCTGCACCACAGTGCTGGTGGCTGTGCACCTGTTTGCGCTCATGATC
AGCACCTGCATCCTGCCCAACATCGAGGCGGTGAGCAACGTGCACAATCTCAACTCGGTC
AAGGAGTCCCCCCATGAGCGCATGCACCGCCACATCGAGCTGGCCTGGGCCTTCTCCACC
GTCATCGGCACGCTGCTCTTCCTAGCTGAGGTGGTGCTGCTCTGCTGGGTCAAGTTCTTG
CCCCTCAAGAAGCAGCCAGGCCAGCCAAGGCCCACCAGCAAGCCCCCCGCCAGTGGCGCA
GCAGCCAACGTCAGCACCAGCGGCATCACCCCGGGCCAGGCAGCTGCCATCGCCTCGACC
ACCATCATGGTGCCCTTCGGCCTGATCTTTATCGTCTTCGCCGTCCACTTCTACCGCTCA
CTGGTTAGCCATAAGACTGACCGACAGTTCCAGGAGCTCAACGAGCTGGCGGAGTTTGCC
CGCTTACAGGACCAGCTGGACCACAGAGGGGACCACCCCCTGACGCCCGGCAGCCACTAT
GCCTAG
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:25896
Chromosome Location12
LocusNot Available
References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  3. Feske S, Prakriya M, Rao A, Lewis RS: A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients. J Exp Med. 2005 Sep 5;202(5):651-62. 16147976
  4. Soboloff J, Spassova MA, Tang XD, Hewavitharana T, Xu W, Gill DL: Orai1 and STIM reconstitute store-operated calcium channel function. J Biol Chem. 2006 Jul 28;281(30):20661-5. Epub 2006 Jun 9. 16766533
  5. Mercer JC, Dehaven WI, Smyth JT, Wedel B, Boyles RR, Bird GS, Putney JW Jr: Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1. J Biol Chem. 2006 Aug 25;281(34):24979-90. Epub 2006 Jun 28. 16807233
  6. Peinelt C, Vig M, Koomoa DL, Beck A, Nadler MJ, Koblan-Huberson M, Lis A, Fleig A, Penner R, Kinet JP: Amplification of CRAC current by STIM1 and CRACM1 (Orai1). Nat Cell Biol. 2006 Jul;8(7):771-3. Epub 2006 May 30. 16733527
  7. Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP: CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science. 2006 May 26;312(5777):1220-3. Epub 2006 Apr 27. 16645049
  8. Parvez S, Beck A, Peinelt C, Soboloff J, Lis A, Monteilh-Zoller M, Gill DL, Fleig A, Penner R: STIM2 protein mediates distinct store-dependent and store-independent modes of CRAC channel activation. FASEB J. 2008 Mar;22(3):752-61. Epub 2007 Sep 28. 17905723
  9. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  10. Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED, Raunser S, Walz T, Garcia KC, Dolmetsch RE, Lewis RS: STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell. 2009 Mar 6;136(5):876-90. doi: 10.1016/j.cell.2009.02.014. Epub 2009 Feb 26. 19249086
  11. Krapivinsky G, Krapivinsky L, Stotz SC, Manasian Y, Clapham DE: POST, partner of stromal interaction molecule 1 (STIM1), targets STIM1 to multiple transporters. Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19234-9. doi: 10.1073/pnas.1117231108. Epub 2011 Nov 14. 22084111
  12. Fukushima M, Tomita T, Janoshazi A, Putney JW: Alternative translation initiation gives rise to two isoforms of Orai1 with distinct plasma membrane mobilities. J Cell Sci. 2012 Sep 15;125(Pt 18):4354-61. doi: 10.1242/jcs.104919. Epub 2012 May 28. 22641696
  13. Srikanth S, Jew M, Kim KD, Yee MK, Abramson J, Gwack Y: Junctate is a Ca2+-sensing structural component of Orai1 and stromal interaction molecule 1 (STIM1). Proc Natl Acad Sci U S A. 2012 May 29;109(22):8682-7. doi: 10.1073/pnas.1200667109. Epub 2012 May 14. 22586105
  14. Srikanth S, Jung HJ, Kim KD, Souda P, Whitelegge J, Gwack Y: A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that stabilizes CRAC channels in T cells. Nat Cell Biol. 2010 May;12(5):436-46. doi: 10.1038/ncb2045. Epub 2010 Apr 25. 20418871
  15. Lee JE, Jeon IS, Han NE, Song HJ, Kim EG, Choi JW, Song KD, Lee HK, Choi JK: Ubiquilin 1 interacts with Orai1 to regulate calcium mobilization. Mol Cells. 2013 Jan;35(1):41-6. doi: 10.1007/s10059-013-2268-7. Epub 2013 Jan 9. 23307288
  16. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  17. Nesin V, Wiley G, Kousi M, Ong EC, Lehmann T, Nicholl DJ, Suri M, Shahrizaila N, Katsanis N, Gaffney PM, Wierenga KJ, Tsiokas L: Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis. Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4197-202. doi: 10.1073/pnas.1312520111. Epub 2014 Mar 3. 24591628
  18. Liu Y, Zheng X, Mueller GA, Sobhany M, DeRose EF, Zhang Y, London RE, Birnbaumer L: Crystal structure of calmodulin binding domain of orai1 in complex with Ca2+ calmodulin displays a unique binding mode. J Biol Chem. 2012 Dec 14;287(51):43030-41. doi: 10.1074/jbc.M112.380964. Epub 2012 Oct 29. 23109337
  19. Stathopulos PB, Schindl R, Fahrner M, Zheng L, Gasmi-Seabrook GM, Muik M, Romanin C, Ikura M: STIM1/Orai1 coiled-coil interplay in the regulation of store-operated calcium entry. Nat Commun. 2013;4:2963. doi: 10.1038/ncomms3963. 24351972
  20. Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A: A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature. 2006 May 11;441(7090):179-85. Epub 2006 Apr 2. 16582901