Q99LI2 · CLCC1_MOUSE
- ProteinChloride channel CLIC-like protein 1
- GeneClcc1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids539 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Anion-selective channel with Ca2+-dependent and voltage-independent gating. Permeable to small monovalent anions with selectivity for bromide > chloride > nitrate > fluoride (PubMed:37142673).
Operates in the endoplasmic reticulum (ER) membrane where it mediates chloride efflux to compensate for the loss of positive charges from the ER lumen upon Ca2+ release. Contributes to the maintenance of ER Ca2+ pools and activation of unfolded protein response to prevent accumulation of misfolded proteins in the ER lumen. Particularly involved in ER homeostasis mechanisms underlying motor neurons and retinal photoreceptors survival (PubMed:25698737, PubMed:30157172, PubMed:37142673).
Operates in the endoplasmic reticulum (ER) membrane where it mediates chloride efflux to compensate for the loss of positive charges from the ER lumen upon Ca2+ release. Contributes to the maintenance of ER Ca2+ pools and activation of unfolded protein response to prevent accumulation of misfolded proteins in the ER lumen. Particularly involved in ER homeostasis mechanisms underlying motor neurons and retinal photoreceptors survival (PubMed:25698737, PubMed:30157172, PubMed:37142673).
Catalytic activity
- chloride(in) = chloride(out)
- bromide(in) = bromide(out)
- nitrate(in) = nitrate(out)
- fluoride(in) = fluoride(out)
Activity regulation
Activated by membrane phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2, PIP2). Inhibited by lumenal Ca2+.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 25 | Ca2+-mediated inhibition of channel activity | ||||
Sequence: D | ||||||
Site | 181 | Ca2+-mediated inhibition of channel activity | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chloride channel complex | |
Cellular Component | cytoplasm | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | Golgi apparatus | |
Cellular Component | Golgi membrane | |
Cellular Component | mitochondria-associated endoplasmic reticulum membrane contact site | |
Cellular Component | nuclear membrane | |
Cellular Component | nucleus | |
Molecular Function | chloride channel activity | |
Molecular Function | identical protein binding | |
Biological Process | chloride transport | |
Biological Process | endoplasmic reticulum calcium ion homeostasis |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameChloride channel CLIC-like protein 1
- 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 accessionQ99LI2
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Note: Within the endoplasmic reticulum (ER), localizes to the mitochondria-associated ER membrane, a zone of contact between the ER and mitochondrial membranes (By similarity).
Enriched in the rough ER (PubMed:37142673).
Enriched in the rough ER (PubMed:37142673).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 19-184 | Lumenal | ||||
Sequence: HDDDWIDPTDMLNYDAASGTMRKSQVRSGTSEKKEVSPDSSEAEELSDCLHRLDSLTHKVDSCEKKKMKDYESQSNPVFRRYLNKILIEAGKLGLPDENKVEMRYDAEILLSRQTLLEIQKFLSGEEWKPGALDDALSDILINFKCHDSEAWKWQFEDYFGVDPYN | ||||||
Transmembrane | 185-205 | Helical | ||||
Sequence: VFMVLLCLLCLVVLVATELWT | ||||||
Topological domain | 206-215 | Cytoplasmic | ||||
Sequence: YVRWYTQMKR | ||||||
Transmembrane | 216-236 | Helical | ||||
Sequence: IFIISFLLSLAWNWIYLYKMA | ||||||
Topological domain | 237-329 | Lumenal | ||||
Sequence: FAQHQANIAGMEPFDNLCAKKMDWTGSLWEWFTSSWTYKDDPCQKYYELLIVNPIWLVPPTKALAITFTNFVTEPLKHIGKGAGEFIKALMKE | ||||||
Transmembrane | 330-350 | Helical | ||||
Sequence: IPVLLQIPVLAILALAVLSFC | ||||||
Topological domain | 351-539 | Cytoplasmic | ||||
Sequence: YGAGRSVPMLRHFGGPDREPPRALEPDDRRRQKGLDYRLHGGAGDADFSYRGPAGSIEQGPYDKMHASKRDALRQRFHSGNKSPEVLRAFDLPDTEAQEHPEVVPSHKSPIMNTNLETGELPGESTPTEYSQSAKDVSGQVPSAGKSSPTVDKAQLKTDSECSPPGGCPPSKEAAVAAHGTEPVSSPCG |
Keywords
- Cellular component
Phenotypes & Variants
Involvement in disease
Disruption phenotype
Embryonic lethal.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 298 | Decreases protein expression and abolishes PIP2-dependent channel activity. Acts as a dominant-negative and suppresses ATP-induced Ca2+ release from the ER. In a knockin mouse model causes enhanced ER stress response, accumulation of unfolded proteins in cerebellum and motor neuron degeneration in compound heterozygosity with a hypomorphic allele; leads to embryonic lethality with a KO allele. | ||||
Sequence: K → A | ||||||
Mutagenesis | 298 | Abolishes PIP2-dependent channel activity. | ||||
Sequence: K → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 29 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-18 | |||||
Sequence: MLCRLLLCECLLLITGYA | ||||||
Chain | PRO_0000297683 | 19-539 | Chloride channel CLIC-like protein 1 | |||
Sequence: HDDDWIDPTDMLNYDAASGTMRKSQVRSGTSEKKEVSPDSSEAEELSDCLHRLDSLTHKVDSCEKKKMKDYESQSNPVFRRYLNKILIEAGKLGLPDENKVEMRYDAEILLSRQTLLEIQKFLSGEEWKPGALDDALSDILINFKCHDSEAWKWQFEDYFGVDPYNVFMVLLCLLCLVVLVATELWTYVRWYTQMKRIFIISFLLSLAWNWIYLYKMAFAQHQANIAGMEPFDNLCAKKMDWTGSLWEWFTSSWTYKDDPCQKYYELLIVNPIWLVPPTKALAITFTNFVTEPLKHIGKGAGEFIKALMKEIPVLLQIPVLAILALAVLSFCYGAGRSVPMLRHFGGPDREPPRALEPDDRRRQKGLDYRLHGGAGDADFSYRGPAGSIEQGPYDKMHASKRDALRQRFHSGNKSPEVLRAFDLPDTEAQEHPEVVPSHKSPIMNTNLETGELPGESTPTEYSQSAKDVSGQVPSAGKSSPTVDKAQLKTDSECSPPGGCPPSKEAAVAAHGTEPVSSPCG | ||||||
Modified residue | 429 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 433 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 459 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 476 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 498 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 513 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 521 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in cerebellum (at protein level).
Gene expression databases
Interaction
Subunit
Homomultimers (PubMed:37142673).
Interacts with mitochondrial protein PIGBOS1 (via C-terminus); the interaction occurs at the mitochondria-associated endoplasmic reticulum (ER) membrane, a zone of contact between the ER and mitochondrial membranes, but does not appear to play a role in ER-mitochondria tethering and is not affected by ER stress (By similarity).
Interacts with CALR (By similarity).
Interacts with mitochondrial protein PIGBOS1 (via C-terminus); the interaction occurs at the mitochondria-associated endoplasmic reticulum (ER) membrane, a zone of contact between the ER and mitochondrial membranes, but does not appear to play a role in ER-mitochondria tethering and is not affected by ER stress (By similarity).
Interacts with CALR (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 41-61 | Disordered | ||||
Sequence: KSQVRSGTSEKKEVSPDSSEA | ||||||
Compositional bias | 45-61 | Basic and acidic residues | ||||
Sequence: RSGTSEKKEVSPDSSEA | ||||||
Region | 361-410 | Disordered | ||||
Sequence: RHFGGPDREPPRALEPDDRRRQKGLDYRLHGGAGDADFSYRGPAGSIEQG | ||||||
Compositional bias | 365-390 | Basic and acidic residues | ||||
Sequence: GPDREPPRALEPDDRRRQKGLDYRLH | ||||||
Region | 444-539 | Disordered | ||||
Sequence: DTEAQEHPEVVPSHKSPIMNTNLETGELPGESTPTEYSQSAKDVSGQVPSAGKSSPTVDKAQLKTDSECSPPGGCPPSKEAAVAAHGTEPVSSPCG | ||||||
Compositional bias | 458-507 | Polar residues | ||||
Sequence: KSPIMNTNLETGELPGESTPTEYSQSAKDVSGQVPSAGKSSPTVDKAQLK |
Sequence similarities
Belongs to the chloride channel MCLC family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length539
- Mass (Da)60,621
- Last updated2001-06-01 v1
- Checksum252A3E095B56C1C4
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 45-61 | Basic and acidic residues | ||||
Sequence: RSGTSEKKEVSPDSSEA | ||||||
Compositional bias | 365-390 | Basic and acidic residues | ||||
Sequence: GPDREPPRALEPDDRRRQKGLDYRLH | ||||||
Compositional bias | 458-507 | Polar residues | ||||
Sequence: KSPIMNTNLETGELPGESTPTEYSQSAKDVSGQVPSAGKSSPTVDKAQLK |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK169803 EMBL· GenBank· DDBJ | BAE41377.1 EMBL· GenBank· DDBJ | mRNA | ||
AK171296 EMBL· GenBank· DDBJ | BAE42376.1 EMBL· GenBank· DDBJ | mRNA | ||
AL671917 EMBL· GenBank· DDBJ | CAM17753.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
AL671917 EMBL· GenBank· DDBJ | CAM17754.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC003247 EMBL· GenBank· DDBJ | AAH03247.1 EMBL· GenBank· DDBJ | mRNA |