Q6P8G8 · ORAI3_MOUSE
- ProteinProtein orai-3
- GeneOrai3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids290 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Pore-forming subunit of two major inward rectifying Ca2+ channels at the plasma membrane: Ca2+ release-activated Ca2+ (CRAC) channels and arachidonate-regulated Ca2+-selective (ARC) channels. Assembles with ORAI1 and ORAI2 to form hexameric CRAC channels that mediate Ca2+ influx upon depletion of endoplasmic reticulum Ca2+ store and channel activation by Ca2+ sensor STIM1, a process known as store-operated Ca2+ entry (SOCE). Various pore subunit combinations may account for distinct CRAC channel spatiotemporal and cell-type specific dynamics. ORAI1 mainly contributes to the generation of Ca2+ plateaus involved in sustained Ca2+ entry and is dispensable for cytosolic Ca2+ oscillations, whereas ORAI2 and ORAI3 generate oscillatory patterns. CRAC channels assemble in Ca2+ signaling microdomains where Ca2+ influx is coupled to calmodulin and calcineurin signaling and activation of NFAT transcription factors recruited to ORAI1 via AKAP5. CRAC channels are the main pathway for Ca2+ influx in T cells and promote the immune response to pathogens by activating NFAT-dependent cytokine and chemokine transcription. Assembles with ORAI1 to form channels that mediate store-independent Ca2+ influx in response to inflammatory metabolites arachidonate or its derivative leukotriene C4, termed ARC and LRC channels respectively.
Catalytic activity
- Ca2+(in) = Ca2+(out)This reaction proceeds in the backward direction.
Activity regulation
CRAC channels are regulated by fast Ca2+-dependent inactivation (FCDI), a mechanism that limits Ca2+ influx and cell toxicity. ORAI3 subunit displays prominent FCDI. Inhibited by lanthanides such as Gd3+ ions.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 81 | Confers selective permeability to Ca2+ ions | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | membrane | |
Cellular Component | plasma membrane | |
Molecular Function | store-operated calcium channel activity | |
Biological Process | store-operated calcium entry |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameProtein orai-3
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ6P8G8
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: Colocalizes with STIM1 upon store depletion.
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 63-82 | Helical | ||||
Sequence: ASSRTSALLSGFAMVAMVEV | ||||||
Transmembrane | 95-115 | Helical | ||||
Sequence: LVAFSACTTVLVAVHLFALMV | ||||||
Transmembrane | 157-177 | Helical | ||||
Sequence: LGTFLFLAEVVLVGWVKFVPI | ||||||
Transmembrane | 239-259 | Helical | ||||
Sequence: AAMASTAIMVPVGLVFMAFAL |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000234396 | 1-290 | Protein orai-3 | |||
Sequence: MKGGEGDTGEQAPLNPEVDSPAGSATYREFVHRGYLDLMGASQHSLRALSWRRLYLSRAKLKASSRTSALLSGFAMVAMVEVQLENDHEYPPGLLVAFSACTTVLVAVHLFALMVSTCLLPHIEAVSNIHNLNSVHQSPHQRLHRYVELAWGFSTALGTFLFLAEVVLVGWVKFVPIGAPMGKPAPVVPMSQVPPVTVSLSLASNLTPSSASITTSQQPSKACPPRQVCDSAHGPGWQAAMASTAIMVPVGLVFMAFALHFYRSLVAHKTDRHKQELEELSRLQGELQAV | ||||||
Modified residue | 42 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 45 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Oligomerizes in homomeric and heteromeric ORAI complexes. Native CRAC channels most likely consist of hexameric ORAI heteromers, implying that diverse ORAI1, ORAI2 and ORAI3 subunit combinations with distinct biophysical properties can operate in a cell-type specific way. ARC channels are heteropentamers consisting of three ORAI1 and two ORAI3 subunits. Interacts with STIM1; this regulates channel activity. Interacts with CRACR2A/EFCAB4B.
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-21 | Disordered | ||||
Sequence: MKGGEGDTGEQAPLNPEVDSP |
Sequence similarities
Belongs to the Orai family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length290
- Mass (Da)31,358
- Last updated2004-07-05 v1
- ChecksumF702164F9F1EB44B
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK136955 EMBL· GenBank· DDBJ | BAE23186.1 EMBL· GenBank· DDBJ | mRNA | ||
BC061259 EMBL· GenBank· DDBJ | AAH61259.1 EMBL· GenBank· DDBJ | mRNA |