CLCN2
entrez
1181
canonical
uniprot
P51788
canonical
ensembl
ENSG00000114859
resolver
ensp
ENSP00000265593
resolver
ensp
ENSP00000345056
resolver
ensp
ENSP00000391928
resolver
ensp
ENSP00000400425
resolver
ensp
ENSP00000551326
resolver
ensp
ENSP00000662308
resolver
ensp
ENSP00000777794
resolver
genesymbol
CLCN2
resolver
hgnc
HGNC:2020
resolver
uniprot
B4DQT9
resolver
uniprot
B4DZ58
resolver
uniprot
E9PBD9
resolver
uniprot
E9PCD2
resolver
uniprot
O14864
resolver
uniprot
Q6IPA9
resolver
uniprot
Q8WU13
resolver
uniprot_entry
CLCN2_HUMAN
resolver
uniprot_sec
B4DQT9
resolver
uniprot_sec
B4DZ58
resolver
uniprot_sec
E9PBD9
resolver
uniprot_sec
E9PCD2
resolver
uniprot_sec
O14864
resolver
uniprot_sec
Q6IPA9
resolver
uniprot_sec
Q8WU13
resolver
activity_regulation
ACTIVITY REGULATION: Common gate kinetics are down-regulated by intracellular ATP (PubMed:23632988). Inhibited by AK-42, a derivative of meclofenamate (PubMed:38345841). Inhibited by Cd(2+) (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P35525, ECO:0000250|UniProtKB:Q9R0A1, ECO:0000250|UniProtKB:Q9WU45, ECO:0000269|PubMed:23632988, ECO:0000269|PubMed:38345841}.
uniprot
proteins
amino_acid_sequence
MAAAAAEEGMEPRALQYEQTLMYGRYTQDLGAFAKEEAARIRLGGPEPWKGPPSSRAAPELLEYGRSRCARCRVCSVRCHKFLVSRVGEDWIFLVLLGLLMALVSWVMDYAIAACLQAQQWMSRGLNTSILLQYLAWVTYPVVLITFSAGFTQILAPQAVGSGIPEMKTILRGVVLKEYLTLKTFIAKVIGLTCALGSGMPLGKEGPFVHIASMCAALLSKFLSLFGGIYENESRNTEMLAAACAVGVGCCFAAPIGGVLFSIEVTSTFFAVRNYWRGFFAATFSAFIFRVLAVWNRDEETITALFKTRFRLDFPFDLQELPAFAVIGIASGFGGALFVYLNRKIVQVMRKQKTINRFLMRKRLLFPALVTLLISTLTFPPGFGQFMAGQLSQKETLVTLFDNRTWVRQGLVEELEPPSTSQAWNPPRANVFLTLVIFILMKFWMSALATTIPVPCGAFMPVFVIGAAFGRLVGESMAAWFPDGIHTDSSTYRIVPGGYAVVGAAALAGAVTHTVSTAVIVFELTGQIAHILPVMIAVILANAVAQSLQPSLYDSIIRIKKLPYLPELGWGRHQQYRVRVEDIMVRDVPHVALSCTFRDLRLALHRTKGRMLALVESPESMILLGSIERSQVVALLGAQLSPARRRQHMQERRATQTSPLSDQEGPPTPEASVCFQVNTEDSAFPAARGETHKPLKPALKRGPSVTRNLGESPTGSAESAGIALRSLFCGSPPPEAASEKLESCEKRKLKRVRISLASDADLEGEMSPEEILEWEEQQLDEPVNFSDCKIDPAPFQLVERTSLHKTHTIFSLLGVDHAYVTSIGRLIGIVTLKELRKAIEGSVTAQGVKVRPPLASFRDSATSSSDTETTEVHALWGPHSRHGLPREGSPSDSDDKCQ
uniprot
proteins
disease_involvement
DISEASE: Epilepsy, idiopathic generalized 11 (EIG11) [MIM:607628]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. {ECO:0000269|PubMed:19191339, ECO:0000269|PubMed:23632988}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Juvenile absence epilepsy 2 (JAE2) [MIM:607628]: A subtype of idiopathic generalized epilepsy characterized by onset occurring around puberty, absence seizures, generalized tonic-clonic seizures (GTCS), GTCS on awakening, and myoclonic seizures. {ECO:0000269|PubMed:19710712, ECO:0000269|PubMed:23632988}. Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Juvenile myoclonic epilepsy 8 (EJM8) [MIM:607628]: A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. {ECO:0000269|PubMed:19191339}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Leukoencephalopathy with ataxia (LKPAT) [MIM:615651]: An autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles, suggesting myelin microvacuolation. Clinical features include ataxia and unstable gait. More variable abnormalities may include visual field defects, headaches, and learning disabilities. {ECO:0000269|PubMed:23707145, ECO:0000269|PubMed:36964785}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hyperaldosteronism, familial, 2 (HALD2) [MIM:605635]: An autosomal dominant disorder characterized by elevated plasma aldosterone level and hypertension of varying severity even within members of the same family. Hypokalemia is observed in some patients. In HALD2, hypertension does not improve with glucocorticoid treatment. {ECO:0000269|PubMed:29403011, ECO:0000269|PubMed:29403012}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:16155254, PubMed:17567819, PubMed:19191339, PubMed:23632988, PubMed:29403011, PubMed:29403012, PubMed:36964785, PubMed:38345841). 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:19191339, PubMed:22405205, PubMed:23707145). 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 (PubMed:29403011, PubMed:29403012). Contributes to chloride conductance in retinal pigment epithelium involved in phagocytosis of shed photoreceptor outer segments and photoreceptor renewal (PubMed:36964785). Conducts chloride currents at the basolateral membrane of epithelial cells with a role in chloride reabsorption rather than secretion (By similarity) (PubMed:16155254). Permeable to small monovalent anions with chloride > thiocyanate > bromide > nitrate > iodide ion selectivity (By similarity) (PubMed:29403012). {ECO:0000250|UniProtKB:P35525, ECO:0000250|UniProtKB:Q9R0A1, ECO:0000269|PubMed:16155254, ECO:0000269|PubMed:17567819, ECO:0000269|PubMed:19191339, ECO:0000269|PubMed:22405205, ECO:0000269|PubMed:23632988, ECO:0000269|PubMed:23707145, ECO:0000269|PubMed:29403011, ECO:0000269|PubMed:29403012, ECO:0000269|PubMed:36964785, ECO:0000269|PubMed:38345841}.
uniprot
proteins
mass_dalton
98535
uniprot
proteins
mutagenesis
MUTAGEN 14..28; /note="Missing: Results in larger currents, faster activation kinetics and less rectification."; /evidence="ECO:0000269|PubMed:38345841"; MUTAGEN 812; /note="L->A: Missorted to apical membrane of epithelial cells; when associated with A-813."; /evidence="ECO:0000269|PubMed:16155254"; MUTAGEN 813; /note="L->A: Missorted to apical membrane of epithelial cells; when associated with A-812."; /evidence="ECO:0000269|PubMed:16155254
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
10198195
uniprot
proteins
pubmed
12612585
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16155254
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
17567819
uniprot
proteins
pubmed
17762171
uniprot
proteins
pubmed
19191339
uniprot
proteins
pubmed
19200853
uniprot
proteins
pubmed
19710712
uniprot
proteins
pubmed
19710717
uniprot
proteins
pubmed
22405205
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23632988
uniprot
proteins
pubmed
23707145
uniprot
proteins
pubmed
29403011
uniprot
proteins
pubmed
29403012
uniprot
proteins
pubmed
36964785
uniprot
proteins
pubmed
38345841
uniprot
proteins
pubmed
7795595
uniprot
proteins
sequence_length
898
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22405205, ECO:0000269|PubMed:23707145, ECO:0000269|PubMed:29403011, ECO:0000269|PubMed:36964785, ECO:0000269|PubMed:38345841}; Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:16155254}; 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:22405205, PubMed:23707145). {ECO:0000250|UniProtKB:P35525, ECO:0000250|UniProtKB:Q9R0A1, ECO:0000269|PubMed:16155254, ECO:0000269|PubMed:22405205, ECO:0000269|PubMed:23707145}.
uniprot
proteins
transmembrane_region
TRANSMEM 88..121; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 130..155; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 180..198; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 205..223; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 275..295; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 321..349; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 358..377; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 429..449; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 457..480; /note="Helical"; /evidence="ECO:0000250"; TRANSMEM 531..548; /note="Helical"; /evidence="ECO:0000250
uniprot
proteins