Clcn2
entrez
12724
canonical
uniprot
Q9R0A1
canonical
ensembl
ENSMUSG00000022843
resolver
ensp
ENSMUSP00000007207
resolver
ensp
ENSMUSP00000178542
resolver
ensp
ENSMUSP00000178549
resolver
ensp
ENSMUSP00000178573
resolver
enst
ENSMUST00000007207
resolver
genesymbol
Clcn2
resolver
genesymbol_syn
Clc2
resolver
uniprot
Q0VBC2
resolver
uniprot
Q9WUJ9
resolver
uniprot_entry
CLCN2_MOUSE
resolver
uniprot_sec
Q0VBC2
resolver
uniprot_sec
Q9WUJ9
resolver
activity_regulation
ACTIVITY REGULATION: Common gate kinetics are down-regulated by intracellular ATP. Inhibited by AK-42, a derivative of meclofenamate (By similarity). Inhibited by Cd(2+) (PubMed:18801913). Inhibited by Zn(2+) and PKC activation (By similarity). Inhibited at acidic pH (By similarity). CCLN2:HEPACAM channel conductance is up-regulated upon hypo-osmolarity (PubMed:26666914). {ECO:0000250|UniProtKB:P35525, ECO:0000250|UniProtKB:P51788, ECO:0000250|UniProtKB:Q9WU45, ECO:0000269|PubMed:18801913, ECO:0000269|PubMed:26666914}.
uniprot
proteins
amino_acid_sequence
MAAATAAAAAAAAAGEGMEPRALQYEQTLMYGRYTQELGAFAKEEAARIRLGGPEPWKGSPSARATPELLEYGQSRCARCRICSVRCHKFLVSRVGEDWIFLVLLGLLMALVSWAMDYAIAVCLQAQQWMSRGLNTNILLQYLAWVTYPVVLITFSAGFTQILAPQAVGSGIPEMKTILRGVVLKEYLTLKTFVAKVIGLTCALGSGMPLGKEGPFVHIASMCAALLSKFLSLFGGIYEHESRNTEMLAAACAVGVGCCFAAPIGGVLFSIEVTSTFFAVRNYWRGFFAATFSAFIFRVLAVWNRDEETITALFKTRFRLDFPFDLQELPAFAVIGIASGFGGALFVYLNRKIVQVMRKQKTINRFLMRKRLLFPALVTLLISTLTFPPGFGQFMAGQLSQKETLVTLFDNRTWVRQGLVEDLELPSTSQAWSPPRANVFLTLVIFILMKFWMSALATTIPVPCGAFMPVFVIGAAFGRLVGESMAAWFPDGIHTDSSTYRIVPGGYAVVGAAALAGAVTHTVSTAVIVFELTGQIAHILPVMIAVILANAVAQSLQPSLYDSIIRIKKLPYLPELGWGRHQQYRVRVEDIMVRDVPHVALSCTFRDLRLALHRTKGRMLALVESPESMILLGSIERSQVVALLGAQLSPARRRQHMQKLRKAQLSPPSDQESPPSSETSIRFQVNTEDSGFSGAHGQTHKPLKPALKRGPSNSTSLQEGTTGNMESAGIALRSLFCGSPPLEATSELEKSESCDKRKLKRVRISLASDSDPEAEMSPEEILEWEEQQLDEPVNFSDCKIDPAPFQLVERTSLHKTHTIFSLLGVDHAYVTSIGRLIGIVTLKELRKAIEGSVTAQGVKVRPPLASFRDSATSSSDTETTEVHALWGPRSRHGLPREGTPSDSDDKCQ
uniprot
proteins
function
FUNCTION: Voltage-gated and osmosensitive chloride channel. Forms a homodimeric channel where each subunit has its own ion conduction pathway. Conducts double-barreled currents controlled by two types of gates, two fast glutamate gates that control each subunit independently and a slow common gate that opens and shuts off both subunits simultaneously. Displays inward rectification currents activated upon membrane hyperpolarization and extracellular hypotonicity (PubMed:18801913, PubMed:20357128, PubMed:26666914). Contributes to chloride conductance involved in neuron excitability. In hippocampal neurons, generates a significant part of resting membrane conductance and provides an additional chloride efflux pathway to prevent chloride accumulation in dendrites upon GABA receptor activation. In glia, associates with the auxiliary subunit HEPACAM/GlialCAM at astrocytic processes and myelinated fiber tracts where it may regulate transcellular chloride flux buffering extracellular chloride and potassium concentrations (PubMed:17567819, PubMed:20357128, PubMed:22405205). Regulates aldosterone production in adrenal glands. The opening of CLCN2 channels at hyperpolarized membrane potentials in the glomerulosa causes cell membrane depolarization, activation of voltage-gated calcium channels and increased expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis (By similarity) (PubMed:29403012). Contributes to chloride conductance in retinal pigment epithelium involved in phagocytosis of shed photoreceptor outer segments and photoreceptor renewal (By similarity). Conducts chloride currents at the basolateral membrane of epithelial cells with a role in chloride reabsorption rather than secretion (By similarity) (PubMed:18801913, PubMed:22079595). Permeable to small monovalent anions with chloride > thiocyanate > bromide > nitrate > iodide ion selectivity (PubMed:26666914). {ECO:0000250|UniProtKB:P35525, ECO:0000250|UniProtKB:P51788, ECO:0000269|PubMed:17567819, ECO:0000269|PubMed:18801913, ECO:0000269|PubMed:20357128, ECO:0000269|PubMed:22079595, ECO:0000269|PubMed:22405205, ECO:0000269|PubMed:26666914, ECO:0000269|PubMed:29403012}.
uniprot
proteins
mass_dalton
99447
uniprot
proteins
mutagenesis
MUTAGEN 538; /note="H->F: Results in increased channel conductance at acidic pH."; /evidence="ECO:0000269|PubMed:26666914
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. Activated by dephosphorylation. {ECO:0000250|UniProtKB:P35525}.
uniprot
proteins
protein_family
Chloride channel (TC 2.A.49) family
uniprot
proteins
protein_family
ClC-2/CLCN2 subfamily
uniprot
proteins
pubmed
10524221
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16155254
uniprot
proteins
pubmed
17567819
uniprot
proteins
pubmed
18801913
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20357128
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22079595
uniprot
proteins
pubmed
22405205
uniprot
proteins
pubmed
26666914
uniprot
proteins
pubmed
29403011
uniprot
proteins
pubmed
29403012
uniprot
proteins
sequence_length
908
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P35525, ECO:0000269|PubMed:22405205}; Multi-pass membrane protein. Myelin membrane {ECO:0000269|PubMed:17567819, ECO:0000269|PubMed:22405205}. Basolateral cell membrane {ECO:0000269|PubMed:16155254, ECO:0000269|PubMed:18801913, ECO:0000269|PubMed:22079595}; Multi-pass membrane protein {ECO:0000255}. Cell projection, dendritic spine membrane {ECO:0000250|UniProtKB:P35525}; Multi-pass membrane protein {ECO:0000255}. Cell projection, axon {ECO:0000250|UniProtKB:P35525}. Note=Sorting to the basolateral membrane is mediated by AP-1 clathrin adapter (PubMed:16155254). Localizes at axon initial segments and dendritic shaft and spikes. Colocalizes with HEPACAM and GFAP at astrocyte end-foot in contact with brain capillaries and other glial cells (By similarity) (PubMed:17567819, PubMed:22405205). {ECO:0000250|UniProtKB:P35525, ECO:0000269|PubMed:16155254, ECO:0000269|PubMed:17567819, ECO:0000269|PubMed:22405205}.
uniprot
proteins
transmembrane_region
TRANSMEM 96..129; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 138..163; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 188..206; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 213..231; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 283..303; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 329..357; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 366..385; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 437..457; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 465..488; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 539..556; /note="Helical"; /evidence="ECO:0000250
uniprot
proteins