Q8R502 · LRC8C_MOUSE
- ProteinVolume-regulated anion channel subunit LRRC8C
- GeneLrrc8c
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids803 (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:29769723).
The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity).
Plays a redundant role in the efflux of amino acids, such as aspartate and glutamate, 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 (By similarity).
May play a role in adipogenesis (PubMed:15184384, PubMed:15564382, PubMed:21804215).
The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity).
Plays a redundant role in the efflux of amino acids, such as aspartate and glutamate, 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 (By similarity).
May play a role in adipogenesis (PubMed:15184384, PubMed:15564382, PubMed:21804215).
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 | |
Cellular Component | endoplasmic reticulum 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 | cellular response to osmotic stress | |
Biological Process | cyclic-GMP-AMP transmembrane import across plasma membrane | |
Biological Process | fat cell differentiation | |
Biological Process | monoatomic anion transmembrane transport | |
Biological Process | protein hexamerization | |
Biological Process | taurine transmembrane transport |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameVolume-regulated anion channel subunit LRRC8C
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8R502
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: In the absence of LRRC8A, resides primarily in a cytoplasmic compartment, probably the endoplasmic reticulum. Requires LRRC8A for expression at the cell membrane.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-22 | Cytoplasmic | ||||
Sequence: MIPVTEFRQFSEQQPAFRVLKP | ||||||
Transmembrane | 23-43 | Helical | ||||
Sequence: WWDVFTDYLSVAMLMIGVFGC | ||||||
Topological domain | 44-125 | Extracellular | ||||
Sequence: TLQVMQDKIICLPKRVQPAQNHSSVPNVSQAVISTTPLPPPKPSPTNPATVEMKGLKTDLDLQQYSFINQMCYERALHWYAK | ||||||
Transmembrane | 126-146 | Helical | ||||
Sequence: YFPYLVLIHTLVFMLCSNFWF | ||||||
Topological domain | 147-266 | Cytoplasmic | ||||
Sequence: KFPGSSSKIEHFISILGKCFDSPWTTRALSEVSGEDSEEKDNRKNNMNRSGTIQSGPEGNLVRSQSLKSIPEKFVVDKSAAGALDKKEGEQAKALFEKVKKFRLHVEEGDILYAMYVRQT | ||||||
Transmembrane | 267-287 | Helical | ||||
Sequence: VLKVIKFLIIIAYNSALVSKV | ||||||
Topological domain | 288-320 | Extracellular | ||||
Sequence: QFTVDCNVDIQDMTGYKNFSCNHTMAHLFSKLS | ||||||
Transmembrane | 321-341 | Helical | ||||
Sequence: FCYLCFVSIYGLTCLYTLYWL | ||||||
Topological domain | 342-803 | Cytoplasmic | ||||
Sequence: FYRSLREYSFEYVRQETGIDDIPDVKNDFAFMLHMIDQYDPLYSKRFAVFLSEVSENKLKQLNLNNEWTPDKLRQKLQTNAHNRLELPLIMLSGLPDTVFEITELQSLKLEIIKNVMIPATIAQLDNLQELCLHQCSVKIHSAALSFLKENLKVLSVKFDDMRELPPWMYGLRNLEELYLVGSLSHDISKNVTLESLRDLKSLKILSIKSNVSKIPQAVVDVSSHLQKMCVHNDGTKLVMLNNLKKMTNLTELELVHCDLERIPHAVFSLLSLQELDLKENNLKSIEEIVSFQHLRKLTVLKLWYNSIAYIPEHIKKLTSLERLFFSHNKVEVLPSHLFLCNKIRYLDLSYNDIRFIPPEIGVLQSLQYFSITCNKVESLPDELYFCKKLKTLKIGKNSLSVLSPKIGNLLFLSYLDIKGNHFEVLPPELGDCRALKRAGLVVEDALFETLPSDVREQMKAD |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice do not show remarkable changes in body weight or the weight of white adipose tissue on a chow diet, but display significantly lower body weights and fat mass than wild-type mice when fed a high-fat diet. Moreover, improved insulin resistance induced by the high-fat diet is observed.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 105 | No effect on channel activity of the complex with LRRC8A. | ||||
Sequence: L → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 56 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, disulfide bond, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000076248 | 1-803 | Volume-regulated anion channel subunit LRRC8C | |||
Sequence: MIPVTEFRQFSEQQPAFRVLKPWWDVFTDYLSVAMLMIGVFGCTLQVMQDKIICLPKRVQPAQNHSSVPNVSQAVISTTPLPPPKPSPTNPATVEMKGLKTDLDLQQYSFINQMCYERALHWYAKYFPYLVLIHTLVFMLCSNFWFKFPGSSSKIEHFISILGKCFDSPWTTRALSEVSGEDSEEKDNRKNNMNRSGTIQSGPEGNLVRSQSLKSIPEKFVVDKSAAGALDKKEGEQAKALFEKVKKFRLHVEEGDILYAMYVRQTVLKVIKFLIIIAYNSALVSKVQFTVDCNVDIQDMTGYKNFSCNHTMAHLFSKLSFCYLCFVSIYGLTCLYTLYWLFYRSLREYSFEYVRQETGIDDIPDVKNDFAFMLHMIDQYDPLYSKRFAVFLSEVSENKLKQLNLNNEWTPDKLRQKLQTNAHNRLELPLIMLSGLPDTVFEITELQSLKLEIIKNVMIPATIAQLDNLQELCLHQCSVKIHSAALSFLKENLKVLSVKFDDMRELPPWMYGLRNLEELYLVGSLSHDISKNVTLESLRDLKSLKILSIKSNVSKIPQAVVDVSSHLQKMCVHNDGTKLVMLNNLKKMTNLTELELVHCDLERIPHAVFSLLSLQELDLKENNLKSIEEIVSFQHLRKLTVLKLWYNSIAYIPEHIKKLTSLERLFFSHNKVEVLPSHLFLCNKIRYLDLSYNDIRFIPPEIGVLQSLQYFSITCNKVESLPDELYFCKKLKTLKIGKNSLSVLSPKIGNLLFLSYLDIKGNHFEVLPPELGDCRALKRAGLVVEDALFETLPSDVREQMKAD | ||||||
Disulfide bond | 54↔308 | |||||
Sequence: CLPKRVQPAQNHSSVPNVSQAVISTTPLPPPKPSPTNPATVEMKGLKTDLDLQQYSFINQMCYERALHWYAKYFPYLVLIHTLVFMLCSNFWFKFPGSSSKIEHFISILGKCFDSPWTTRALSEVSGEDSEEKDNRKNNMNRSGTIQSGPEGNLVRSQSLKSIPEKFVVDKSAAGALDKKEGEQAKALFEKVKKFRLHVEEGDILYAMYVRQTVLKVIKFLIIIAYNSALVSKVQFTVDCNVDIQDMTGYKNFSC | ||||||
Disulfide bond | 115↔293 | |||||
Sequence: CYERALHWYAKYFPYLVLIHTLVFMLCSNFWFKFPGSSSKIEHFISILGKCFDSPWTTRALSEVSGEDSEEKDNRKNNMNRSGTIQSGPEGNLVRSQSLKSIPEKFVVDKSAAGALDKKEGEQAKALFEKVKKFRLHVEEGDILYAMYVRQTVLKVIKFLIIIAYNSALVSKVQFTVDC | ||||||
Modified residue | 212 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 215 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed at very low levels in adipose tissue.
Induction
Induced during the earliest stages of adipogenesis.
Gene expression databases
Interaction
Subunit
Heterohexamer (PubMed:29769723).
Oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8B, LRRC8D and/or LRRC8E) to form a heterohexamer (PubMed:24782309, PubMed:29769723).
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)
Oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8B, LRRC8D and/or LRRC8E) to form a heterohexamer (PubMed:24782309, PubMed:29769723).
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
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 177-206 | Disordered | ||||
Sequence: EVSGEDSEEKDNRKNNMNRSGTIQSGPEGN | ||||||
Compositional bias | 178-192 | Basic and acidic residues | ||||
Sequence: VSGEDSEEKDNRKNN | ||||||
Repeat | 397-420 | LRR 1 | ||||
Sequence: ENKLKQLNLNNEWTPDKLRQKLQT | ||||||
Repeat | 421-443 | LRR 2 | ||||
Sequence: NAHNRLELPLIMLSGLPDTVFEI | ||||||
Repeat | 446-466 | LRR 3 | ||||
Sequence: LQSLKLEIIKNVMIPATIAQL | ||||||
Repeat | 467-488 | LRR 4 | ||||
Sequence: DNLQELCLHQCSVKIHSAALSF | ||||||
Repeat | 490-513 | LRR 5 | ||||
Sequence: KENLKVLSVKFDDMRELPPWMYGL | ||||||
Repeat | 515-537 | LRR 6 | ||||
Sequence: NLEELYLVGSLSHDISKNVTLES | ||||||
Repeat | 541-563 | LRR 7 | ||||
Sequence: LKSLKILSIKSNVSKIPQAVVDV | ||||||
Repeat | 566-586 | LRR 8 | ||||
Sequence: HLQKMCVHNDGTKLVMLNNLK | ||||||
Repeat | 588-611 | LRR 9 | ||||
Sequence: MTNLTELELVHCDLERIPHAVFSL | ||||||
Repeat | 613-635 | LRR 10 | ||||
Sequence: SLQELDLKENNLKSIEEIVSFQH | ||||||
Repeat | 637-659 | LRR 11 | ||||
Sequence: RKLTVLKLWYNSIAYIPEHIKKL | ||||||
Repeat | 660-682 | LRR 12 | ||||
Sequence: TSLERLFFSHNKVEVLPSHLFLC | ||||||
Repeat | 684-705 | LRR 13 | ||||
Sequence: KIRYLDLSYNDIRFIPPEIGVL | ||||||
Repeat | 706-728 | LRR 14 | ||||
Sequence: QSLQYFSITCNKVESLPDELYFC | ||||||
Repeat | 730-751 | LRR 15 | ||||
Sequence: KLKTLKIGKNSLSVLSPKIGNL | ||||||
Repeat | 752-774 | LRR 16 | ||||
Sequence: LFLSYLDIKGNHFEVLPPELGDC | ||||||
Repeat | 776-799 | LRR 17 | ||||
Sequence: ALKRAGLVVEDALFETLPSDVREQ |
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.
The cytoplasmic N-terminus preceding the first transmembrane (residues 1-22) regulates volume-regulated anion channel (VRAC) conductance, ion permeability and inactivation gating.
Sequence similarities
Belongs to the LRRC8 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length803
- Mass (Da)92,372
- Last updated2002-06-01 v1
- ChecksumE99DAC364FF980B5
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 178 | in Ref. 2; BAC40706 | ||||
Sequence: V → A | ||||||
Compositional bias | 178-192 | Basic and acidic residues | ||||
Sequence: VSGEDSEEKDNRKNN | ||||||
Sequence conflict | 653 | in Ref. 2; BAE41199 | ||||
Sequence: P → A | ||||||
Sequence conflict | 781 | in Ref. 3; AAH25473/AAH26572 | ||||
Sequence: G → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB081508 EMBL· GenBank· DDBJ | BAB86302.1 EMBL· GenBank· DDBJ | mRNA | ||
AK169492 EMBL· GenBank· DDBJ | BAE41199.1 EMBL· GenBank· DDBJ | mRNA | ||
AK089024 EMBL· GenBank· DDBJ | BAC40706.1 EMBL· GenBank· DDBJ | mRNA | ||
AK142337 EMBL· GenBank· DDBJ | BAE25036.1 EMBL· GenBank· DDBJ | mRNA | ||
BC025473 EMBL· GenBank· DDBJ | AAH25473.1 EMBL· GenBank· DDBJ | mRNA | ||
BC026572 EMBL· GenBank· DDBJ | AAH26572.1 EMBL· GenBank· DDBJ | mRNA |