Clcc1
entrez
229725
canonical
uniprot
Q99LI2
canonical
ensembl
ENSMUSG00000027884
resolver
ensp
ENSMUSP00000029483
resolver
ensp
ENSMUSP00000102220
resolver
ensp
ENSMUSP00000102224
resolver
ensp
ENSMUSP00000198820
resolver
ensp
ENSMUSP00000198833
resolver
ensp
ENSMUSP00000198842
resolver
enst
ENSMUST00000029483
resolver
enst
ENSMUST00000106609
resolver
enst
ENSMUST00000106613
resolver
genesymbol
Clcc1
resolver
uniprot
A2AEK9
resolver
uniprot
A2AEM2
resolver
uniprot_entry
A2AEM2_MOUSE
resolver
uniprot_entry
CLCC1_MOUSE
resolver
uniprot_sec
A2AEK9
resolver
activity_regulation
ACTIVITY REGULATION: Activated by membrane phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2, PIP2). Inhibited by lumenal Ca(2+). {ECO:0000269|PubMed:37142673}.
uniprot
proteins
amino_acid_sequence
MLCRLLLCECLLLITGYAHDDDWIDPTDMLNYDAASGTMRKSQVRSGTSEKKEVSPDSSEAEELSDCLHRLDSLTHKVDSCEKKKMKDYESQSNPVFRRYLNKILIEAGKLGLPDENKVEMRYDAEILLSRQTLLEIQKFLSGEEWKPGALDDALSDILINFKCHDSEAWKWQFEDYFGVDPYNVFMVLLCLLCLVVLVATELWTYVRWYTQMKRIFIISFLLSLAWNWIYLYKMAFAQHQANIAGMEPFDNLCAKKMDWTGSLWEWFTSSWTYKDDPCQKYYELLIVNPIWLVPPTKALAITFTNFVTEPLKHIGKGAGEFIKALMKEIPVLLQIPVLAILALAVLSFCYGAGRSVPMLRHFGGPDREPPRALEPDDRRRQKGLDYRLHGGAGDADFSYRGPAGSIEQGPYDKMHASKRDALRQRFHSGNKSPEVLRAFDLPDTEAQEHPEVVPSHKSPIMNTNLETGELPGESTPTEYSQSAKDVSGQVPSAGKSSPTVDKAQLKTDSECSPPGGCPPSKEAAVAAHGTEPVSSPCG
uniprot
proteins
disease_involvement
DISEASE: Note=NM2453 (NM/NM) mice carrying a spontaneous hypomorphic CLCC1 allele develop progressive cerebellar granule neuron degeneration with muscle atrophy and peripheral neuropathy reminiscent of amyotrophic lateral sclerosis. {ECO:0000269|PubMed:25698737}.
uniprot
proteins
function
FUNCTION: Anion-selective channel with Ca(2+)-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 Ca(2+) release. Contributes to the maintenance of ER Ca(2+) 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). {ECO:0000269|PubMed:25698737, ECO:0000269|PubMed:30157172, ECO:0000269|PubMed:37142673}.
uniprot
proteins
mass_dalton
60621
uniprot
proteins
mutagenesis
MUTAGEN 298; /note="K->A: Decreases protein expression and abolishes PIP2-dependent channel activity. Acts as a dominant-negative and suppresses ATP-induced Ca(2+) 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."; /evidence="ECO:0000269|PubMed:37142673"; MUTAGEN 298; /note="K->E: Abolishes PIP2-dependent channel activity."; /evidence="ECO:0000269|PubMed:37142673
uniprot
proteins
protein_family
Chloride channel MCLC family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
25698737
uniprot
proteins
pubmed
30157172
uniprot
proteins
pubmed
37142673
uniprot
proteins
sequence_length
539
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:37142673}; Multi-pass membrane protein {ECO:0000255}. 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). {ECO:0000250|UniProtKB:Q96S66, ECO:0000269|PubMed:37142673}.
uniprot
proteins
transmembrane_region
TRANSMEM 185..205; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 216..236; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 330..350; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins