Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q96D31 (CRCM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium release-activated calcium channel protein 1
Alternative name(s):
Protein orai-1
Transmembrane protein 142A
Gene names
Name:ORAI1
Synonyms:CRACM1, TMEM142A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length301 AA.
Sequence statusComplete.
Protein existenceEvidence 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.10 Ref.15 Ref.16

Subunit structure

Interacts with STIM1 and STIM2; this regulates channel activity. Interacts with CALM; this may displace STIM1 and STIM2 and might thereby modulate channel activity. 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. Interacts with ASPH (isoform 8) Ref.8 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15

Subcellular location

Cell membrane; Multi-pass membrane protein. Note: Isoform beta is more mobile in the plasma membrane. Ref.7 Ref.10 Ref.11 Ref.15 Ref.16

Post-translational modification

N-glycosylated. Ref.10

Involvement in disease

Immunodeficiency 9 (IMD9) [MIM:612782]: An immune disorder characterized by recurrent infections, impaired activation and proliferative response of T-cells, decreased T-cell production of cytokines, and normal lymphocytes counts and serum immunoglobulin levels. In surviving patients ectodermal dysplasia with anhidrosis and non-progressive myopathy may be observed.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.16

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.

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]
Isoform alpha (identifier: Q96D31-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform beta (identifier: Q96D31-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 301301Calcium release-activated calcium channel protein 1
PRO_0000234381

Regions

Topological domain1 – 8787Cytoplasmic Ref.10
Transmembrane88 – 10518Helical; Potential
Topological domain106 – 11914Extracellular Potential
Transmembrane120 – 14021Helical; Potential
Topological domain141 – 17333Cytoplasmic Potential
Transmembrane174 – 19421Helical; Potential
Topological domain195 – 23440Extracellular Potential
Transmembrane235 – 25521Helical; Potential
Topological domain256 – 30146Cytoplasmic Ref.10
Region70 – 9021Interaction with STIM1
Region272 – 29221Interaction with STIM1
Compositional bias3 – 4745Pro-rich

Amino acid modifications

Modified residue2951Phosphothreonine Ref.9
Modified residue2981Phosphoserine Ref.9
Glycosylation2231N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 7070Missing in isoform beta.
VSP_044421
Natural variant911R → W in IMD9. Ref.16
VAR_026226
Natural variant2181S → G. Ref.1 Ref.2
Corresponds to variant rs3741596 [ dbSNP | Ensembl ].
VAR_038608

Experimental info

Mutagenesis85 – 873KLK → ALA: Impairs interaction with EFCAB4B/CRACR2A. Ref.13
Mutagenesis2811R → A: Strongly reduces calcium current. Ref.15
Mutagenesis2841D → A: Reduces the maximum current; when associated with A-287 and A-291. Ref.15
Mutagenesis2861L → S: Strongly reduces calcium current. Ref.15
Mutagenesis2871D → A: Reduces the maximum current; when associated with A-284 and A-291. Ref.15
Mutagenesis2891R → A: Strongly reduces calcium current. Ref.15
Mutagenesis2911D → A: Reduces the maximum current; when associated with A-284 and A-287. Ref.15
Sequence conflict2551V → F in BAB55068. Ref.2

Secondary structure

..... 301
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform alpha [UniParc].

Last modified May 16, 2006. Version 2.
Checksum: F85F7C06F36628D4

FASTA30132,668
        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 

« Hide

Isoform beta [UniParc].

Checksum: 0F7EEBB6DADB9005
Show »

FASTA23125,337

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA), 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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 22-301 (ISOFORM ALPHA), 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] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IMD9.
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-295 AND SER-298, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1."
Park C.Y., Hoover P.J., Mullins F.M., Bachhawat P., Covington E.D., Raunser S., Walz T., Garcia K.C., Dolmetsch R.E., Lewis R.S.
Cell 136:876-890(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH STIM1, SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, GLYCOSYLATION.
[11]"Alternative translation initiation gives rise to two isoforms of orai1 with distinct plasma membrane mobilities."
Fukushima M., Tomita T., Janoshazi A., Putney J.W.
J. Cell Sci. 125:4354-4361(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE INITIATION, SUBCELLULAR LOCATION.
[12]"Junctate is a Ca2+-sensing structural component of Orai1 and stromal interaction molecule 1 (STIM1)."
Srikanth S., Jew M., Kim K.D., Yee M.K., Abramson J., Gwack Y.
Proc. Natl. Acad. Sci. U.S.A. 109:8682-8687(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ASPH.
[13]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EFCAB4B, MUTAGENESIS OF 85-LYS--LYS-87.
[14]"Crystal structure of calmodulin binding domain of orai1 in complex with Ca2+ calmodulin displays a unique binding mode."
Liu Y., Zheng X., Mueller G.A., Sobhany M., DeRose E.F., Zhang Y., London R.E., Birnbaumer L.
J. Biol. Chem. 287:43030-43041(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 69-88 IN COMPLEX WITH CALM, INTERACTION WITH CALM.
[15]"STIM1/Orai1 coiled-coil interplay in the regulation of store-operated calcium entry."
Stathopulos P.B., Schindl R., Fahrner M., Zheng L., Gasmi-Seabrook G.M., Muik M., Romanin C., Ikura M.
Nat. Commun. 4:2963-2963(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 272-292 IN COMPLEX WITH STIM1, INTERACTION WITH STIM1, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-281; ASP-284; LEU-286; ASP-287; ARG-289 AND ASP-291.
[16]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IMD9 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.
CCDSCCDS41851.1. [Q96D31-1]
RefSeqNP_116179.2. NM_032790.3. [Q96D31-1]
UniGeneHs.55148.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2MAKNMR-B/D272-292[»]
4EHQX-ray1.90G69-88[»]
ProteinModelPortalQ96D31.
SMRQ96D31. Positions 74-292.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124321. 2 interactions.
DIPDIP-46289N.
IntActQ96D31. 4 interactions.
MINTMINT-6780078.
STRING9606.ENSP00000328216.

Chemistry

BindingDBQ96D31.
ChEMBLCHEMBL3038476.

Protein family/group databases

TCDB1.A.52.1.1. the ca(2+) release-activated ca(2+) (crac) channel (crac-c) family.

PTM databases

PhosphoSiteQ96D31.

Polymorphism databases

DMDM97180269.

Proteomic databases

MaxQBQ96D31.
PaxDbQ96D31.
PRIDEQ96D31.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330079; ENSP00000328216; ENSG00000182500.
GeneID84876.
KEGGhsa:84876.
UCSCuc021rff.1. human. [Q96D31-1]

Organism-specific databases

CTD84876.
GeneCardsGC12P122064.
HGNCHGNC:25896. ORAI1.
HPAHPA016583.
MIM610277. gene.
612782. phenotype.
neXtProtNX_Q96D31.
Orphanet317428. Combined immunodeficiency due to ORAI1 deficiency.
PharmGKBPA162398445.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG263788.
HOGENOMHOG000246925.
HOVERGENHBG081343.
InParanoidQ96D31.
KOK16056.
OrthoDBEOG7G1V73.
PhylomeDBQ96D31.
TreeFamTF313576.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressQ96D31.
BgeeQ96D31.
CleanExHS_ORAI1.
GenevestigatorQ96D31.

Family and domain databases

InterProIPR012446. CRAC_channel.
[Graphical view]
PfamPF07856. Orai-1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiORAI1.
GenomeRNAi84876.
NextBio75181.
PROQ96D31.
SOURCESearch...

Entry information

Entry nameCRCM1_HUMAN
AccessionPrimary (citable) accession number: Q96D31
Secondary accession number(s): Q3MHV3 expand/collapse secondary AC list , Q6DHX2, Q96BP7, Q96K71
Entry history
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: July 9, 2014
This is version 98 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM