Q96D31 (CRCM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcium release-activated calcium channel protein 1

Alternative name(s):
Protein orai-1
Transmembrane protein 142A

Gene names

Name:	ORAI1
Synonyms:	CRACM1, TMEM142A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	301 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ca2+ release-activated Ca2+ (CRAC) channel subunit which mediates Ca2+ influx following depletion of intracellular Ca2+ stores and channel activation by the Ca2+ sensor, STIM1. CRAC channels are the main pathway for Ca2+ influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT. Ref.4 Ref.5 Ref.6 Ref.7 Ref.11
Subunit structure	Interacts with STIM1 and STIM2. Interacts with EFCAB4B/CRACR2A; the interaction is direct and takes place in absence of Ca2+. Forms a complex with EFCAB4B/CRACR2A and STIM1 at low concentration of Ca2+, the complex dissociates at elevated Ca2+ concentrations. Ref.8 Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.7 Ref.11.
Involvement in disease	Defects in ORAI1 are the cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 1 (IDTICED1) [MIM:612782]. IDTICED1 is an immune disorder characterized by recurrent infections, impaired T-cell activation and proliferative response, decreased T-cell production of cytokines, and normal lymphocytes counts and serum immunoglobulin levels. In surviving patients ectodermal dysplasia with anhydrosis and non-progressive myopathy may be observed. Ref.3 Ref.11
Miscellaneous	In Greek mythology, the 'Orai' are the keepers of the gates of heaven: Eunomia (order or harmony), Dike (justice) and Eirene (peace).
Sequence similarities	Belongs to the Orai family.
Sequence caution	The sequence AAH13386.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAI04634.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAB55068.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Adaptive immunity Calcium transport Immunity Ion transport Transport
Cellular component	Cell membrane Membrane
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Calcium channel Ionic channel
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	platelet activation Traceable author statement. Source: Reactome positive regulation of calcium ion transport Inferred from direct assay Ref.7Ref.6Ref.4Ref.5. Source: UniProtKB
Cellular component	integral to plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction Ref.8Ref.10. Source: UniProtKB store-operated calcium channel activity Inferred from direct assay Ref.7Ref.6Ref.4Ref.5. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATP2C2	O75185	10	EBI-2291476,EBI-2939806
EFCAB4B	Q9BSW2	6	EBI-2291476,EBI-739773
STIM1	Q13586	9	EBI-2291476,EBI-448878

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 301	301	Calcium release-activated calcium channel protein 1		PRO_0000234381
Regions
	Topological domain	1 – 87	87	Cytoplasmic Potential
	Transmembrane	88 – 105	18	Helical; Potential
	Topological domain	106 – 119	14	Extracellular Potential
	Transmembrane	120 – 140	21	Helical; Potential
	Topological domain	141 – 173	33	Cytoplasmic Potential
	Transmembrane	174 – 194	21	Helical; Potential
	Topological domain	195 – 234	40	Extracellular Potential
	Transmembrane	235 – 255	21	Helical; Potential
	Topological domain	256 – 301	46	Cytoplasmic Potential
	Compositional bias	3 – 47	45	Pro-rich
Amino acid modifications
	Modified residue	295	1	Phosphothreonine Ref.9
	Modified residue	298	1	Phosphoserine Ref.9
	Glycosylation	223	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	91	1	R → W in IDTICED1. Ref.11		VAR_026226
	Natural variant	218	1	S → G. [dbSNP:rs3741596] Ref.1 Ref.2		VAR_038608
Experimental info
	Mutagenesis	85 – 87	3	KLK → ALA: Impairs interaction with EFCAB4B/CRACR2A. Ref.10
	Sequence conflict	255	1	V → F in BAB55068. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q96D31 [UniParc]. Last modified May 16, 2006. Version 2. Checksum: F85F7C06F36628D4	FASTA	301	32,668
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-218. Tissue: Bone marrow, Ovary, Prostate and Uterus.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 22-301, VARIANT GLY-218. Tissue: Mammary gland.
[3]	"A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients." Feske S., Prakriya M., Rao A., Lewis R.S. J. Exp. Med. 202:651-662(2005) [PubMed: 16147976] [Abstract] Cited for: INVOLVEMENT IN IDTICED1.
[4]	"Orai1 and STIM reconstitute store-operated calcium channel function." Soboloff J., Spassova M.A., Tang X.D., Hewavitharana T., Xu W., Gill D.L. J. Biol. Chem. 281:20661-20665(2006) [PubMed: 16766533] [Abstract] Cited for: FUNCTION.
[5]	"Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1." Mercer J.C., Dehaven W.I., Smyth J.T., Wedel B., Boyles R.R., Bird G.S., Putney J.W. Jr. J. Biol. Chem. 281:24979-24990(2006) [PubMed: 16807233] [Abstract] Cited for: FUNCTION.
[6]	"Amplification of CRAC current by STIM1 and CRACM1 (Orai1)." 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. Nat. Cell Biol. 8:771-773(2006) [PubMed: 16733527] [Abstract] Cited for: FUNCTION.
[7]	"CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry." 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. Science 312:1220-1223(2006) [PubMed: 16645049] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]	"STIM2 protein mediates distinct store-dependent and store-independent modes of CRAC channel activation." Parvez S., Beck A., Peinelt C., Soboloff J., Lis A., Monteilh-Zoller M., Gill D.L., Fleig A., Penner R. FASEB J. 22:752-761(2008) [PubMed: 17905723] [Abstract] Cited for: INTERACTION WITH STIM1 AND STIM2.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-295 AND SER-298, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that stabilizes CRAC channels in T cells." Srikanth S., Jung H.J., Kim K.D., Souda P., Whitelegge J., Gwack Y. Nat. Cell Biol. 12:436-446(2010) [PubMed: 20418871] [Abstract] Cited for: INTERACTION WITH EFCAB4B, MUTAGENESIS OF 85-LYS--LYS-87.
[11]	"A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function." Feske S., Gwack Y., Prakriya M., Srikanth S., Puppel S.-H., Tanasa B., Hogan P.G., Lewis R.S., Daly M., Rao A. Nature 441:179-185(2006) [PubMed: 16582901] [Abstract] Cited for: VARIANT IDTICED1 TRP-91, SUBCELLULAR LOCATION, FUNCTION.
+	Additional computationally mapped references.

Web resources

ORAI1base

ORAI1 mutation db

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC013386 mRNA. Translation: AAH13386.1. Different initiation. BC015369 mRNA. Translation: AAH15369.2. BC075831 mRNA. Translation: AAH75831.1. BC104633 mRNA. Translation: AAI04634.1. Different initiation. AK027372 mRNA. Translation: BAB55068.1. Different initiation.
IPI	IPI00303699.
RefSeq	NP_116179.2. NM_032790.3.
UniGene	Hs.55148.
3D structure databases
ProteinModelPortal	Q96D31.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-46289N.
IntAct	Q96D31. 5 interactions.
STRING	Q96D31.
Protein family/group databases
TCDB	1.A.52.1.1. Ca2+ release-activated Ca2+ (CRAC) channel (CRAC-C) family.
PTM databases
PhosphoSite	Q96D31.
Polymorphism databases
DMDM	97180269.
Proteomic databases
PRIDE	Q96D31.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000330079; ENSP00000328216; ENSG00000182500.
GeneID	84876.
KEGG	hsa:84876.
UCSC	uc009zxg.1. human.
Organism-specific databases
CTD	84876.
GeneCards	GC12P122064.
H-InvDB	HIX0022443.
HGNC	HGNC:25896. ORAI1.
HPA	HPA016583.
MIM	610277. gene. 612782. phenotype.
neXtProt	NX_Q96D31.
Orphanet	169090. Severe combined immunodeficiency due to CRAC channel dysfunction.
PharmGKB	PA162398445.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15497.
GeneTree	ENSGT00390000015354.
HOGENOM	HBG715505.
HOVERGEN	HBG081343.
InParanoid	Q96D31.
OrthoDB	EOG4WH8MR.
Enzyme and pathway databases
Pathway_Interaction_DB	tcrpathway. TCR signaling in naive CD4+ T cells. cd8tcrpathway. TCR signaling in naive CD8+ T cells.
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	Q96D31.
Bgee	Q96D31.
CleanEx	HS_ORAI1.
Genevestigator	Q96D31.
GermOnline	ENSG00000182500. Homo sapiens.
Family and domain databases
InterPro	IPR012446. CRAC_channel. [Graphical view]
Pfam	PF07856. Orai-1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	75181.
SOURCE	Search...

Entry information

Entry name

CRCM1_HUMAN

Accession

Primary (citable) accession number: Q96D31
Secondary accession number(s): Q3MHV3 , Q6DHX2, Q96BP7, Q96K71

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2006
Last sequence update:	May 16, 2006
Last modified:	January 25, 2012
This is version 70 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.