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UniProtKB/Swiss-Prot entry Q96D31


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name CRCM1_HUMAN
Primary accession number Q96D31
Secondary accession numbers Q3MHV3 Q6DHX2 Q96BP7 Q96K71
Integrated into Swiss-Prot on May 16, 2006
Sequence was last modified on May 16, 2006 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 44)
Name and origin of the protein
Protein name Calcium release-activated calcium channel protein 1
Synonyms Protein orai-1
Transmembrane protein 142A
Gene name
Name: ORAI1
Synonyms: CRACM1, TMEM142A
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-218.
TISSUE=Bone marrow, Ovary, Prostate, and Uterus;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 22-301, AND VARIANT GLY-218.
TISSUE=Mammary gland;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
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 T.-O., 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. 36:40-45(2004).
[3]
INVOLVEMENT IN CRAC-SCID.
DOI=10.1084/jem.20050687; PubMed=16147976 [NCBI, ExPASy, EBI, Israel, Japan]
Feske S., Prakriya M., Rao A., Lewis R.S.;
"A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients.";
J. Exp. Med. 202:651-662(2005).
[4]
FUNCTION.
DOI=10.1074/jbc.M604589200; PubMed=16807233 [NCBI, ExPASy, EBI, Israel, Japan]
Mercer J.C., Dehaven W.I., Smyth J.T., Wedel B., Boyles R.R., Bird G.S., Putney J.W. Jr.;
"Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1.";
J. Biol. Chem. 281:24979-24990(2006).
[5]
FUNCTION.
DOI=10.1074/jbc.C600126200; PubMed=16766533 [NCBI, ExPASy, EBI, Israel, Japan]
Soboloff J., Spassova M.A., Tang X.D., Hewavitharana T., Xu W., Gill D.L.;
"Orai1 and STIM reconstitute store-operated calcium channel function.";
J. Biol. Chem. 281:20661-20665(2006).
[6]
FUNCTION.
DOI=10.1038/ncb1435; PubMed=16733527 [NCBI, ExPASy, EBI, Israel, Japan]
Peinelt C., Vig M., Koomoa D.L., Beck A., Nadler M.J.S., Koblan-Huberson M., Lis A., Fleig A., Penner R., Kinet J.-P.;
"Amplification of CRAC current by STIM1 and CRACM1 (Orai1).";
Nat. Cell Biol. 8:771-773(2006).
[7]
FUNCTION, AND SUBCELLULAR LOCATION.
DOI=10.1126/science.1127883; PubMed=16645049 [NCBI, ExPASy, EBI, Israel, Japan]
Vig M., Peinelt C., Beck A., Koomoa D.L., Rabah D., Koblan-Huberson M., Kraft S., Turner H., Fleig A., Penner R., Kinet J.-P.;
"CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry.";
Science 312:1220-1223(2006).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-295 AND SER-298, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan]
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[9]
VARIANT CRAC-SCID TRP-91, SUBCELLULAR LOCATION, AND FUNCTION.
DOI=10.1038/nature04702; PubMed=16582901 [NCBI, ExPASy, EBI, Israel, Japan]
Feske S., Gwack Y., Prakriya M., Srikanth S., Puppel S.-H., Tanasa B., Hogan P.G., Lewis R.S., Daly M., Rao A.;
"A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function.";
Nature 441:179-185(2006).
Comments
  • FUNCTION: Ca(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. 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.
  • SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
  • DISEASE: Defects in ORAI1 are a cause of severe combined immunodeficiency with CRAC channel dysfunction (CRAC-SCID) [MIM:610277]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.
  • MISCELLANEOUS: In Greek mythology, the 'Orai' are the keepers of the gates of heaven: Eunomia (order or harmony), Dike (justice) and Eirene (peace).
  • SIMILARITY: Belongs to the Orai family.
  • WEB RESOURCE: Name=ORAI1base; Note=ORAI1 mutation db; URL="http://bioinf.uta.fi/ORAI1base/";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
BC013386; AAH13386.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC015369; AAH15369.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC075831; AAH75831.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC104633; AAI04634.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK027372; BAB55068.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00303699; -.
RefSeq NP_116179.2; -.
UniGene Hs.55148
3D structure databases
ModBase Q96D31.
Protein family/group databases
TCDB 1.A.52.1.1; Ca2+ release-activated Ca2+ (CRAC) channel (CRAC-C) family.
PTM databases
PhosphoSite Q96D31; -.
Enzyme and pathway databases
Pathway_Interaction_DB tcrpathway; TCR signaling in naive CD4+ T cells.
cd8tcrpathway; TCR signaling in naive CD8+ T cells.
Organism-specific databases
GeneCards GC12P120550; -.
HGNC HGNC:25896; ORAI1.
GenAtlas ORAI1.
HPA HPA016583; -.
MIM 610277; gene+phenotype. [NCBI / EBI]
Gene expression databases
ArrayExpress Q96D31; -.
Bgee Q96D31; -.
CleanEx HS_ORAI1; -.
GermOnline ENSG00000182500; Homo sapiens.
Ontologies
GO
GO:0005887; Cellular component: integral to plasma membrane (inferred from direct assay from UniProtKB).
GO:0005509; Molecular function: calcium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0015279; Molecular function: store-operated calcium channel activity (inferred from direct assay from UniProtKB).
GO:0006816; Biological process: calcium ion transport (inferred from electronic annotation from UniProtKB-KW).
GO:0006955; Biological process: immune response (inferred from electronic annotation from UniProtKB-KW).
GO:0051928; Biological process: positive regulation of calcium ion transport (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR012446; DUF1650.
Graphical view of domain structure.
Pfam PF07856; DUF1650; 1.
Pfam graphical view of domain structure.
Proteomic databases
PRIDE Q96D31; -.
Genome annotation databases
Ensembl ENSG00000182500; Homo sapiens. [Contig view]
GeneID 84876; -.
KEGG hsa:84876; -.
Phylogenomic databases
HOGENOM Q96D31; -.
HOVERGEN Q96D31; -.
Other
NextBio 75181; -.
SOURCE ORAI1; Homo sapiens.
ProtoNet Q96D31.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Calcium; Calcium channel; Calcium transport; Cell membrane; Disease mutation; Glycoprotein; Immune response; Ion transport; Ionic channel; Membrane; Phosphoprotein; SCID; Transmembrane; Transport.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   301  301     Calcium release-activated calcium channel protein 1. PRO_0000234381
TOPO_DOM   1    87  87     Cytoplasmic (Potential). 
TRANSMEM   88   105  18     Potential. 
TOPO_DOM   106   119  14     Extracellular (Potential). 
TRANSMEM   120   140  21     Potential. 
TOPO_DOM   141   173  33     Cytoplasmic (Potential). 
TRANSMEM   174   194  21     Potential. 
TOPO_DOM   195   234  40     Extracellular (Potential). 
TRANSMEM   235   255  21     Potential. 
TOPO_DOM   256   301  46     Cytoplasmic (Potential). 
COMPBIAS   3    47  45     Pro-rich. 
MOD_RES   295   295        Phosphothreonine. 
MOD_RES   298   298        Phosphoserine. 
CARBOHYD   223   223        N-linked (GlcNAc...) (Potential). 
VARIANT   91    91  1     R -> W (in CRAC-SCID). VAR_026226 
VARIANT   218   218  1     S -> G (in dbSNP:rs3741596 [NCBI]). VAR_038608 
CONFLICT   255   255        V -> F (in Ref. 2; BAB55068). 
Sequence information
Length: 301 AA [This is the length of the unprocessed precursor] Molecular weight: 32668 Da [This is the MW of the unprocessed precursor] CRC64: F85F7C06F36628D4 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MHPEPAPPPS RSSPELPPSG GSTTSGSRRS RRRSGDGEPP GAPPPPPSAV TYPDWIGQSY 

        70         80         90        100        110        120 
SEVMSLNEHS MQALSWRKLY LSRAKLKASS RTSALLSGFA MVAMVEVQLD ADHDYPPGLL 

       130        140        150        160        170        180 
IAFSACTTVL VAVHLFALMI STCILPNIEA VSNVHNLNSV KESPHERMHR HIELAWAFST 

       190        200        210        220        230        240 
VIGTLLFLAE VVLLCWVKFL PLKKQPGQPR PTSKPPASGA AANVSTSGIT PGQAAAIAST 

       250        260        270        280        290        300 
TIMVPFGLIF IVFAVHFYRS LVSHKTDRQF QELNELAEFA RLQDQLDHRG DHPLTPGSHY 


A 

Q96D31 in FASTA format

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