Q3KRC6 · LRC8E_RAT
- ProteinVolume-regulated anion channel subunit LRRC8E
- GeneLrrc8e
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids795 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes (PubMed:28833202).
The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity).
Mediates efflux of amino acids, such as aspartate, in response to osmotic stress (By similarity).
The VRAC channel also mediates transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (By similarity).
Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:28833202).
Also plays a role in lysosome homeostasis by forming functional lysosomal VRAC channels in response to low cytoplasmic ionic strength condition: lysosomal VRAC channels are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis (By similarity).
The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity).
Mediates efflux of amino acids, such as aspartate, in response to osmotic stress (By similarity).
The VRAC channel also mediates transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (By similarity).
Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:28833202).
Also plays a role in lysosome homeostasis by forming functional lysosomal VRAC channels in response to low cytoplasmic ionic strength condition: lysosomal VRAC channels are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis (By similarity).
Catalytic activity
- chloride(in) = chloride(out)
- iodide(out) = iodide(in)
- taurine(out) = taurine(in)
- 2',3'-cGAMP(out) = 2',3'-cGAMP(in)This reaction proceeds in the forward and the backward directions.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | lysosomal membrane | |
Cellular Component | monoatomic ion channel complex | |
Cellular Component | plasma membrane | |
Molecular Function | volume-sensitive anion channel activity | |
Biological Process | aspartate transmembrane transport | |
Biological Process | cell volume homeostasis | |
Biological Process | cellular response to osmotic stress | |
Biological Process | cyclic-GMP-AMP transmembrane import across plasma membrane | |
Biological Process | monoatomic anion transmembrane transport |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameVolume-regulated anion channel subunit LRRC8E
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ3KRC6
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Lysosome membrane ; Multi-pass membrane protein
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Note: In the absence of LRRC8A, resides primarily in the endoplasmic reticulum. Requires LRRC8A for localization at the cell membrane or lysosome membrane.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-22 | Cytoplasmic | ||||
Sequence: MIPVAEFKQFTEQQPAFKVLKP | ||||||
Transmembrane | 23-43 | Helical | ||||
Sequence: WWDVLAEYLTVAMLMIGVFGC | ||||||
Topological domain | 44-116 | Extracellular | ||||
Sequence: TLQVTQDKIICLPSHESRENSSEAPCQQLLPQGISEQIGGLRELSGLKNNLDLQQYSFINQLCYETALHWYAK | ||||||
Transmembrane | 117-137 | Helical | ||||
Sequence: YFPYLVVIHTLIFMVCTSFWF | ||||||
Topological domain | 138-264 | Cytoplasmic | ||||
Sequence: KFPGTSSKIEHFISILGKCFDSPWTTRALSEVSGENHKGPAAGRATVTTVTTVGTGTGKVGEGEKEKVLIEPEKVVTEPPAVTLLDKKEGEQAKALFEKVKKFRVHVEEGDILYSMYIRQTVLKVCK | ||||||
Transmembrane | 265-285 | Helical | ||||
Sequence: FFAILVYNLVYVEKISFLVAC | ||||||
Topological domain | 286-312 | Extracellular | ||||
Sequence: RVETSEITGYASFCCNHTKAHLFSKLA | ||||||
Transmembrane | 313-333 | Helical | ||||
Sequence: FCYISFVCVYGITCLYTLYWL | ||||||
Topological domain | 334-795 | Cytoplasmic | ||||
Sequence: FHRPLKEYSFRSVREETGMNDIPDVRNDFAFMLHLIDQYDSLYSKRFAVFLSEVSESRLKQLNLNHEWTPDKLRQKLQRNARGRLELSLCMLPGLPDTVFELSEVEALRLEAICDISFPPGLSQLVNLQELSLLHSPARLPFSSQIFLRDRLKVICVKFEELREVPLWVFGLRGLEELHLEGLFPPEMARGATLESLRELKQLKVLSLRSNAGKVPASVTDVAGHLQRLSLHNDGARLLALNSLKKLAVLRELELVACGLERIPHAIFSLGALQELDLKDNHLRSIEEILSFQHCRKLVILRLWHNQIAYVPEHVRKLRSLEQLYLSHNKLETLPAQLGQCFGLRLLDVSHNGLRSLPPELGLLQSLQHLALSYNALESLPDELFFCHKLRTLLLGYNHLTQFSPHVAALQALSRLELKGNRLEALPEELGDCKGLKKSGLLVEDTLYEGLPAEVREKMEEE |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000076252 | 1-795 | Volume-regulated anion channel subunit LRRC8E | |||
Sequence: MIPVAEFKQFTEQQPAFKVLKPWWDVLAEYLTVAMLMIGVFGCTLQVTQDKIICLPSHESRENSSEAPCQQLLPQGISEQIGGLRELSGLKNNLDLQQYSFINQLCYETALHWYAKYFPYLVVIHTLIFMVCTSFWFKFPGTSSKIEHFISILGKCFDSPWTTRALSEVSGENHKGPAAGRATVTTVTTVGTGTGKVGEGEKEKVLIEPEKVVTEPPAVTLLDKKEGEQAKALFEKVKKFRVHVEEGDILYSMYIRQTVLKVCKFFAILVYNLVYVEKISFLVACRVETSEITGYASFCCNHTKAHLFSKLAFCYISFVCVYGITCLYTLYWLFHRPLKEYSFRSVREETGMNDIPDVRNDFAFMLHLIDQYDSLYSKRFAVFLSEVSESRLKQLNLNHEWTPDKLRQKLQRNARGRLELSLCMLPGLPDTVFELSEVEALRLEAICDISFPPGLSQLVNLQELSLLHSPARLPFSSQIFLRDRLKVICVKFEELREVPLWVFGLRGLEELHLEGLFPPEMARGATLESLRELKQLKVLSLRSNAGKVPASVTDVAGHLQRLSLHNDGARLLALNSLKKLAVLRELELVACGLERIPHAIFSLGALQELDLKDNHLRSIEEILSFQHCRKLVILRLWHNQIAYVPEHVRKLRSLEQLYLSHNKLETLPAQLGQCFGLRLLDVSHNGLRSLPPELGLLQSLQHLALSYNALESLPDELFFCHKLRTLLLGYNHLTQFSPHVAALQALSRLELKGNRLEALPEELGDCKGLKKSGLLVEDTLYEGLPAEVREKMEEE | ||||||
Disulfide bond | 54↔300 | |||||
Sequence: CLPSHESRENSSEAPCQQLLPQGISEQIGGLRELSGLKNNLDLQQYSFINQLCYETALHWYAKYFPYLVVIHTLIFMVCTSFWFKFPGTSSKIEHFISILGKCFDSPWTTRALSEVSGENHKGPAAGRATVTTVTTVGTGTGKVGEGEKEKVLIEPEKVVTEPPAVTLLDKKEGEQAKALFEKVKKFRVHVEEGDILYSMYIRQTVLKVCKFFAILVYNLVYVEKISFLVACRVETSEITGYASFCC | ||||||
Glycosylation | 63 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 301 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Heterohexamer (Probable). Oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8C, LRRC8D and/or LRRC8B) to form a heterohexamer (PubMed:28833202).
Detected in a channel complex that contains LRRC8A, LRRC8C and LRRC8E (By similarity).
In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist (Probable)
Detected in a channel complex that contains LRRC8A, LRRC8C and LRRC8E (By similarity).
In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist (Probable)
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 535-556 | LRR 1 | ||||
Sequence: QLKVLSLRSNAGKVPASVTDVA | ||||||
Repeat | 558-578 | LRR 2 | ||||
Sequence: HLQRLSLHNDGARLLALNSLK | ||||||
Repeat | 582-603 | LRR 3 | ||||
Sequence: VLRELELVACGLERIPHAIFSL | ||||||
Repeat | 605-626 | LRR 4 | ||||
Sequence: ALQELDLKDNHLRSIEEILSFQ | ||||||
Repeat | 630-651 | LRR 5 | ||||
Sequence: KLVILRLWHNQIAYVPEHVRKL | ||||||
Repeat | 653-674 | LRR 6 | ||||
Sequence: SLEQLYLSHNKLETLPAQLGQC | ||||||
Repeat | 676-697 | LRR 7 | ||||
Sequence: GLRLLDVSHNGLRSLPPELGLL | ||||||
Repeat | 699-720 | LRR 8 | ||||
Sequence: SLQHLALSYNALESLPDELFFC | ||||||
Repeat | 722-743 | LRR 9 | ||||
Sequence: KLRTLLLGYNHLTQFSPHVAAL | ||||||
Repeat | 745-766 | LRR 10 | ||||
Sequence: ALSRLELKGNRLEALPEELGDC |
Domain
The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins.
Sequence similarities
Belongs to the LRRC8 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length795
- Mass (Da)90,445
- Last updated2005-11-08 v1
- Checksum17F6795B243632DC
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BC105779 EMBL· GenBank· DDBJ | AAI05780.1 EMBL· GenBank· DDBJ | mRNA |