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Protein

Calcium release-activated calcium channel protein 1

Gene

ORAI1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (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 Ca2+ influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT (PubMed:16582901).9 Publications

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • positive regulation of calcium ion transport Source: UniProtKB
  • regulation of calcium ion transport Source: UniProtKB
  • store-operated calcium entry Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel

Keywords - Biological processi

Adaptive immunity, Calcium transport, Immunity, Ion transport, Transport

Keywords - Ligandi

Calcium, Calmodulin-binding

Enzyme and pathway databases

BioCyciZFISH:G66-32411-MONOMER.
ReactomeiR-HSA-139853. Elevation of cytosolic Ca2+ levels.
R-HSA-5578775. Ion homeostasis.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SIGNORiQ96D31.

Protein family/group databases

TCDBi1.A.52.1.1. the ca(2+) release-activated ca(2+) (crac) channel (crac-c) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium release-activated calcium channel protein 1
Alternative name(s):
Protein orai-1
Transmembrane protein 142A
Gene namesi
Name:ORAI1
Synonyms:CRACM1, TMEM142A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:25896. ORAI1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 87Cytoplasmic1 PublicationAdd BLAST87
Transmembranei88 – 105HelicalSequence analysisAdd BLAST18
Topological domaini106 – 119ExtracellularSequence analysisAdd BLAST14
Transmembranei120 – 140HelicalSequence analysisAdd BLAST21
Topological domaini141 – 173CytoplasmicSequence analysisAdd BLAST33
Transmembranei174 – 194HelicalSequence analysisAdd BLAST21
Topological domaini195 – 234ExtracellularSequence analysisAdd BLAST40
Transmembranei235 – 255HelicalSequence analysisAdd BLAST21
Topological domaini256 – 301Cytoplasmic1 PublicationAdd BLAST46

GO - Cellular componenti

  • autophagosome Source: UniProtKB-SubCell
  • cytoplasmic vesicle Source: UniProtKB-KW
  • integral component of plasma membrane Source: UniProtKB
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 9 (IMD9)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:612782
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02622691R → W in IMD9. 1 PublicationCorresponds to variant rs118203993dbSNPEnsembl.1
Myopathy, tubular aggregate, 2 (TAM2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. TAM2 patients have myopathy and pupillary abnormalities.
See also OMIM:615883
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071473245P → L in TAM2; increases activation of the Ca2+ release-activated Ca2+ (CRAC) channel. 1 PublicationCorresponds to variant rs587777528dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi85 – 87KLK → ALA: Impairs interaction with CRACR2A/EFCAB4B. 1 Publication3
Mutagenesisi281R → A: Strongly reduces calcium current. 1 Publication1
Mutagenesisi284D → A: Reduces the maximum current; when associated with A-287 and A-291. 1 Publication1
Mutagenesisi286L → S: Strongly reduces calcium current. 1 Publication1
Mutagenesisi287D → A: Reduces the maximum current; when associated with A-284 and A-291. 1 Publication1
Mutagenesisi289R → A: Strongly reduces calcium current. 1 Publication1
Mutagenesisi291D → A: Reduces the maximum current; when associated with A-284 and A-287. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi84876.
MalaCardsiORAI1.
MIMi612782. phenotype.
615883. phenotype.
Orphaneti317428. Combined immunodeficiency due to ORAI1 deficiency.
2593. Tubular aggregate myopathy.
PharmGKBiPA162398445.

Chemistry databases

ChEMBLiCHEMBL2384891.

Polymorphism and mutation databases

DMDMi97180269.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002343811 – 301Calcium release-activated calcium channel protein 1Add BLAST301

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi223N-linked (GlcNAc...)Sequence analysis1
Modified residuei295PhosphothreonineCombined sources1
Modified residuei298PhosphoserineCombined sources1

Post-translational modificationi

N-glycosylated.1 Publication
Ubiquitinated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ96D31.
MaxQBiQ96D31.
PaxDbiQ96D31.
PeptideAtlasiQ96D31.
PRIDEiQ96D31.
TopDownProteomicsiQ96D31-2. [Q96D31-2]

PTM databases

iPTMnetiQ96D31.
PhosphoSitePlusiQ96D31.
SwissPalmiQ96D31.

Expressioni

Gene expression databases

BgeeiENSG00000182500.
CleanExiHS_ORAI1.
GenevisibleiQ96D31. HS.

Organism-specific databases

HPAiHPA016583.
HPA061823.

Interactioni

Subunit structurei

Interacts with STIM1 and STIM2; this regulates channel activity (PubMed:17905723, PubMed:19249086, PubMed:24351972). Interacts with CALM; this may displace STIM1 and STIM2 and might thereby modulate channel activity (PubMed:23109337). Interacts with CRACR2A/EFCAB4B; the interaction is direct and takes place in absence of Ca2+ (PubMed:20418871). Forms a complex with CRACR2A/EFCAB4B and STIM1 at low concentration of Ca2+, the complex dissociates at elevated Ca2+ concentrations. Interacts with ASPH (isoform 8) (PubMed:22586105). Interacts with SLC35G1 (PubMed:22084111). Interacts with UBQLN1 (PubMed:23307288).8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-2291476,EBI-2291476
ATP2C2O7518510EBI-2291476,EBI-2939806
CRACR2AQ9BSW26EBI-2291476,EBI-739773
ORAI3Q9BRQ53EBI-2291476,EBI-4279484
STIM1Q1358616EBI-2291476,EBI-448878

Protein-protein interaction databases

BioGridi124321. 3 interactors.
DIPiDIP-46289N.
IntActiQ96D31. 5 interactors.
MINTiMINT-6780078.
STRINGi9606.ENSP00000328216.

Chemistry databases

BindingDBiQ96D31.

Structurei

Secondary structure

1301
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi76 – 86Combined sources11
Helixi272 – 288Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MAKNMR-B/D272-292[»]
4EHQX-ray1.90G69-88[»]
ProteinModelPortaliQ96D31.
SMRiQ96D31.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni70 – 90Interaction with STIM1Add BLAST21
Regioni272 – 292Interaction with STIM1Add BLAST21

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi3 – 47Pro-richAdd BLAST45

Sequence similaritiesi

Belongs to the Orai family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4298. Eukaryota.
ENOG4110DSB. LUCA.
HOGENOMiHOG000246925.
HOVERGENiHBG081343.
InParanoidiQ96D31.
KOiK16056.
OMAiDAEHDYP.
OrthoDBiEOG091G0E4P.
PhylomeDBiQ96D31.
TreeFamiTF313576.

Family and domain databases

InterProiIPR012446. CRAC_channel.
[Graphical view]
PANTHERiPTHR31501. PTHR31501. 2 hits.
PfamiPF07856. Orai-1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform alpha (identifier: Q96D31-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MHPEPAPPPS RSSPELPPSG GSTTSGSRRS RRRSGDGEPP GAPPPPPSAV
60 70 80 90 100
TYPDWIGQSY SEVMSLNEHS MQALSWRKLY LSRAKLKASS RTSALLSGFA
110 120 130 140 150
MVAMVEVQLD ADHDYPPGLL IAFSACTTVL VAVHLFALMI STCILPNIEA
160 170 180 190 200
VSNVHNLNSV KESPHERMHR HIELAWAFST VIGTLLFLAE VVLLCWVKFL
210 220 230 240 250
PLKKQPGQPR PTSKPPASGA AANVSTSGIT PGQAAAIAST TIMVPFGLIF
260 270 280 290 300
IVFAVHFYRS LVSHKTDRQF QELNELAEFA RLQDQLDHRG DHPLTPGSHY

A
Length:301
Mass (Da):32,668
Last modified:May 16, 2006 - v2
Checksum:iF85F7C06F36628D4
GO
Isoform beta (identifier: Q96D31-2) [UniParc]FASTAAdd to basket

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

Show »
Length:231
Mass (Da):25,337
Checksum:i0F7EEBB6DADB9005
GO

Sequence cautioni

The sequence AAH13386 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAI04634 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB55068 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti255V → F in BAB55068 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02622691R → W in IMD9. 1 PublicationCorresponds to variant rs118203993dbSNPEnsembl.1
Natural variantiVAR_038608218S → G.2 PublicationsCorresponds to variant rs3741596dbSNPEnsembl.1
Natural variantiVAR_071473245P → L in TAM2; increases activation of the Ca2+ release-activated Ca2+ (CRAC) channel. 1 PublicationCorresponds to variant rs587777528dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0444211 – 70Missing in isoform beta. CuratedAdd BLAST70

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_116179.2. NM_032790.3. [Q96D31-1]
UniGeneiHs.55148.

Genome annotation databases

EnsembliENST00000616379; ENSP00000480616; ENSG00000276045.
GeneIDi84876.
KEGGihsa:84876.
UCSCiuc031zps.1. human. [Q96D31-1]

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Web resourcesi

ORAI1base

ORAI1 mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_116179.2. NM_032790.3. [Q96D31-1]
UniGeneiHs.55148.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MAKNMR-B/D272-292[»]
4EHQX-ray1.90G69-88[»]
ProteinModelPortaliQ96D31.
SMRiQ96D31.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124321. 3 interactors.
DIPiDIP-46289N.
IntActiQ96D31. 5 interactors.
MINTiMINT-6780078.
STRINGi9606.ENSP00000328216.

Chemistry databases

BindingDBiQ96D31.
ChEMBLiCHEMBL2384891.

Protein family/group databases

TCDBi1.A.52.1.1. the ca(2+) release-activated ca(2+) (crac) channel (crac-c) family.

PTM databases

iPTMnetiQ96D31.
PhosphoSitePlusiQ96D31.
SwissPalmiQ96D31.

Polymorphism and mutation databases

DMDMi97180269.

Proteomic databases

EPDiQ96D31.
MaxQBiQ96D31.
PaxDbiQ96D31.
PeptideAtlasiQ96D31.
PRIDEiQ96D31.
TopDownProteomicsiQ96D31-2. [Q96D31-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000616379; ENSP00000480616; ENSG00000276045.
GeneIDi84876.
KEGGihsa:84876.
UCSCiuc031zps.1. human. [Q96D31-1]

Organism-specific databases

CTDi84876.
DisGeNETi84876.
GeneCardsiORAI1.
HGNCiHGNC:25896. ORAI1.
HPAiHPA016583.
HPA061823.
MalaCardsiORAI1.
MIMi610277. gene.
612782. phenotype.
615883. phenotype.
neXtProtiNX_Q96D31.
Orphaneti317428. Combined immunodeficiency due to ORAI1 deficiency.
2593. Tubular aggregate myopathy.
PharmGKBiPA162398445.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4298. Eukaryota.
ENOG4110DSB. LUCA.
HOGENOMiHOG000246925.
HOVERGENiHBG081343.
InParanoidiQ96D31.
KOiK16056.
OMAiDAEHDYP.
OrthoDBiEOG091G0E4P.
PhylomeDBiQ96D31.
TreeFamiTF313576.

Enzyme and pathway databases

BioCyciZFISH:G66-32411-MONOMER.
ReactomeiR-HSA-139853. Elevation of cytosolic Ca2+ levels.
R-HSA-5578775. Ion homeostasis.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SIGNORiQ96D31.

Miscellaneous databases

GeneWikiiORAI1.
GenomeRNAii84876.
PROiQ96D31.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182500.
CleanExiHS_ORAI1.
GenevisibleiQ96D31. HS.

Family and domain databases

InterProiIPR012446. CRAC_channel.
[Graphical view]
PANTHERiPTHR31501. PTHR31501. 2 hits.
PfamiPF07856. Orai-1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCRCM1_HUMAN
AccessioniPrimary (citable) accession number: Q96D31
Secondary accession number(s): Q3MHV3
, Q6DHX2, Q96BP7, Q96K71
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: November 30, 2016
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

In Greek mythology, the 'Orai' are the keepers of the gates of heaven: Eunomia (order or harmony), Dike (justice) and Eirene (peace).

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.