KCNK1
entrez
3775
canonical
uniprot
O00180
canonical
ensembl
ENSG00000135750
resolver
ensp
ENSP00000355580
resolver
enst
ENST00000366621
resolver
genesymbol
KCNK1
resolver
genesymbol_syn
HOHO1
resolver
genesymbol_syn
KCNO1
resolver
genesymbol_syn
TWIK1
resolver
hgnc
HGNC:6272
resolver
uniprot
Q13307
resolver
uniprot
Q5T5E8
resolver
uniprot_entry
KCNK1_HUMAN
resolver
uniprot_sec
Q13307
resolver
uniprot_sec
Q5T5E8
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by Ba(2+) ions and quinidine (PubMed:8605869). Inhibited by quinine (PubMed:21653227, PubMed:8605869). Is slightly inhibited by 10 mM tetraethylammonium (TEA), and only marginally inhibited by 4-aminopyridine, charybdotoxin and dendrotoxin (PubMed:8605869). Lowering the extracellular pH to below 6.5 transiently activates the channel, and then inhibits channel activity (PubMed:15820677, PubMed:22431633). Inhibited when the intracellular pH is decreased down to pH 6.0, but this may be due to indirect effects (PubMed:8605869). {ECO:0000269|PubMed:15820677, ECO:0000269|PubMed:21653227, ECO:0000269|PubMed:22431633, ECO:0000269|PubMed:8605869}.
uniprot
proteins
amino_acid_sequence
MLQSLAGSSCVRLVERHRSAWCFGFLVLGYLLYLVFGAVVFSSVELPYEDLLRQELRKLKRRFLEEHECLSEQQLEQFLGRVLEASNYGVSVLSNASGNWNWDFTSALFFASTVLSTTGYGHTVPLSDGGKAFCIIYSVIGIPFTLLFLTAVVQRITVHVTRRPVLYFHIRWGFSKQVVAIVHAVLLGFVTVSCFFFIPAAVFSVLEDDWNFLESFYFCFISLSTIGLGDYVPGEGYNQKFRELYKIGITCYLLLGLIAMLVVLETFCELHELKKFRKMFYVKKDKDEDQVHIIEHDQLSFSSITDQAAGMKEDQKQNEPFVATQSSACVDGPANH
uniprot
proteins
function
FUNCTION: Ion channel that contributes to passive transmembrane potassium transport and to the regulation of the resting membrane potential in brain astrocytes, but also in kidney and in other tissues (PubMed:15820677, PubMed:21653227). Forms dimeric channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:22282804). The channel is selective for K(+) ions at physiological potassium concentrations and at neutral pH, but becomes permeable to Na(+) at subphysiological K(+) levels and upon acidification of the extracellular medium (PubMed:21653227, PubMed:22431633). The homodimer has very low potassium channel activity, when expressed in heterologous systems, and can function as weakly inward rectifying potassium channel (PubMed:15820677, PubMed:21653227, PubMed:22431633, PubMed:23169818, PubMed:25001086, PubMed:8605869, PubMed:8978667). Channel activity is modulated by activation of serotonin receptors (By similarity). Heterodimeric channels containing KCNK1 and KCNK2 have much higher activity, and may represent the predominant form in astrocytes (By similarity). Heterodimeric channels containing KCNK1 and KCNK3 or KCNK9 have much higher activity (PubMed:23169818). Heterodimeric channels formed by KCNK1 and KCNK9 may contribute to halothane-sensitive currents (PubMed:23169818). Mediates outward rectifying potassium currents in dentate gyrus granule cells and contributes to the regulation of their resting membrane potential (By similarity). Contributes to the regulation of action potential firing in dentate gyrus granule cells and down-regulates their intrinsic excitability (By similarity). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G protein-coupled receptors, such as F2R and CNR1 (By similarity). Required for normal ion and water transport in the kidney (By similarity). Contributes to the regulation of the resting membrane potential of pancreatic beta cells (By similarity). The low channel activity of homodimeric KCNK1 may be due to sumoylation (PubMed:15820677, PubMed:20498050, PubMed:23169818). The low channel activity may be due to rapid internalization from the cell membrane and retention in recycling endosomes (PubMed:19959478). Permeable to monovalent cations with ion selectivity for K(+) > Rb(+) >> NH4(+) >> Cs(+) = Na(+) = Li(+). {ECO:0000250|UniProtKB:O08581, ECO:0000250|UniProtKB:Q9Z2T2, ECO:0000269|PubMed:15820677, ECO:0000269|PubMed:17693262, ECO:0000269|PubMed:19959478, ECO:0000269|PubMed:20498050, ECO:0000269|PubMed:21653227, ECO:0000269|PubMed:22282804, ECO:0000269|PubMed:22431633, ECO:0000269|PubMed:23169818, ECO:0000269|PubMed:25001086, ECO:0000269|PubMed:8605869, ECO:0000269|PubMed:8978667}.
uniprot
proteins
mass_dalton
38143
uniprot
proteins
mutagenesis
MUTAGEN 69; /note="C->A: Abolishes channel activity and formation of disulfide-linked homodimers."; /evidence="ECO:0000269|PubMed:8978667"; MUTAGEN 95; /note="N->A: Abolishes N-glycosylation."; /evidence="ECO:0000269|PubMed:8978667"; MUTAGEN 108..109; /note="LF->FY: Impairs selectivity for K(+) ions and increases permeability to Na(+) ions, both at pH 7.4 and at pH 6."; /evidence="ECO:0000269|PubMed:22431633"; MUTAGEN 118; /note="T->I: Abolishes change in ion selectivity in the presence of subphysiological K(+) levels."; /evidence="ECO:0000269|PubMed:21653227"; MUTAGEN 122; /note="H->K: Increases channel activity, and has only a minor effect on the inhibition by acidification of the extracellular medium."; /evidence="ECO:0000269|PubMed:22431633"; MUTAGEN 122; /note="H->N: Decreases channel activity and abolishes inhibition by acidification of the extracellular medium."; /evidence="ECO:0000269|PubMed:15820677, ECO:0000269|PubMed:20498050, ECO:0000269|PubMed:22431633"; MUTAGEN 146; /note="L->A,V: Does not increase the low intrinsic channel activity."; /evidence="ECO:0000269|PubMed:25001086"; MUTAGEN 146; /note="L->D: Increases channel activity."; /evidence="ECO:0000269|PubMed:22431633, ECO:0000269|PubMed:25001086"; MUTAGEN 146; /note="L->N,T: Increases channel activity."; /evidence="ECO:0000269|PubMed:25001086"; MUTAGEN 146; /note="L->S: Increases channel activity. Strongly increases channel activity; when associated with S-261."; /evidence="ECO:0000269|PubMed:25001086"; MUTAGEN 161; /note="T->A: No effect on channel activity."; /evidence="ECO:0000269|PubMed:8605869"; MUTAGEN 228; /note="L->F: No effect on selectivity for K(+) ions."; /evidence="ECO:0000269|PubMed:22431633"; MUTAGEN 231; /note="Y->F: Strongly decreases activity of homodimeric channels and of heterodimeric channels formed with KCNK3 and with KCNK9. No effect on location at the cell membrane."; /evidence="ECO:0000269|PubMed:23169818"; MUTAGEN 250; /note="T->L: Slightly decreases the increased permeability to Na(+) ions at pH 6."; /evidence="ECO:0000269|PubMed:22431633"; MUTAGEN 261; /note="L->D,N: Increases channel activity."; /evidence="ECO:0000269|PubMed:25001086"; MUTAGEN 261; /note="L->S: Increases channel activity. Strongly increases channel activity; when associated with S-146."; /evidence="ECO:0000269|PubMed:25001086"; MUTAGEN 274; /note="K->A,C,D,Q,R: Converts the electrically silent channel that is present at the cell membrane to an active channel."; /evidence="ECO:0000269|PubMed:20498050"; MUTAGEN 274; /note="K->E: Converts the electrically silent channel that is present at the cell membrane to an active channel. No effect on retention in recycling endosomes."; /evidence="ECO:0000269|PubMed:15820677, ECO:0000269|PubMed:17693262, ECO:0000269|PubMed:19959478, ECO:0000269|PubMed:20498050, ECO:0000269|PubMed:21653227, ECO:0000269|PubMed:22431633"; MUTAGEN 293..294; /note="II->AA: Strongly increases location at the cell membrane."; /evidence="ECO:0000269|PubMed:19959478"; MUTAGEN 299..336; /note="Missing: No effect on intracellular retention in recycling endosomes."; /evidence="ECO:0000269|PubMed:19959478
uniprot
proteins
post_translational_modification
PTM: Sumoylation is controversial. Sumoylated by UBE2I (PubMed:15820677). Not sumoylated when expressed in xenopus oocytes or mammalian cells (PubMed:17693262). Sumoylation inactivates the channel, but does not interfere with expression at the cell membrane (PubMed:15820677). Sumoylation of a single subunit is sufficient to silence the dimeric channel (PubMed:20498050, PubMed:23169818). Sumoylation of KCNK1 is sufficient to silence heterodimeric channels formed by KCNK1 and KCNK3 or KCNK9 (PubMed:23169818). Desumoylated by SENP1; this activates the channel (PubMed:15820677, PubMed:20498050, PubMed:23169818). Desumoylated by SENP1; this strongly increases halothane-mediated activation of heterodimeric channels formed with KCNK9 (PubMed:23169818). SENP1 treatment has no effect (PubMed:17693262). {ECO:0000269|PubMed:15820677, ECO:0000269|PubMed:17693262, ECO:0000269|PubMed:20498050, ECO:0000269|PubMed:23169818}.
uniprot
proteins
protein_family
Two pore domain potassium channel (TC 1.A.1.8) family
uniprot
proteins
pubmed
11165377
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15820677
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17478540
uniprot
proteins
pubmed
17693262
uniprot
proteins
pubmed
19959478
uniprot
proteins
pubmed
20498050
uniprot
proteins
pubmed
21653227
uniprot
proteins
pubmed
21964404
uniprot
proteins
pubmed
22282804
uniprot
proteins
pubmed
22431633
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23169818
uniprot
proteins
pubmed
25001086
uniprot
proteins
pubmed
25339226
uniprot
proteins
pubmed
25530075
uniprot
proteins
pubmed
8605869
uniprot
proteins
pubmed
8978667
uniprot
proteins
pubmed
9362344
uniprot
proteins
pubmed
9462864
uniprot
proteins
sequence_length
336
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15820677, ECO:0000269|PubMed:17693262, ECO:0000269|PubMed:20498050, ECO:0000269|PubMed:21653227, ECO:0000269|PubMed:22282804, ECO:0000269|PubMed:22431633, ECO:0000269|PubMed:23169818, ECO:0000269|PubMed:25001086, ECO:0000269|PubMed:8605869, ECO:0000269|PubMed:8978667}; Multi-pass membrane protein {ECO:0000269|PubMed:22282804, ECO:0000269|PubMed:8978667, ECO:0000305}. Recycling endosome {ECO:0000269|PubMed:19959478}. Synaptic cell membrane {ECO:0000250|UniProtKB:Q9Z2T2}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:O08581}. Perikaryon {ECO:0000250|UniProtKB:O08581}. Cell projection, dendrite {ECO:0000250|UniProtKB:O08581}. Cell projection {ECO:0000250|UniProtKB:O08581}. Apical cell membrane {ECO:0000269|PubMed:21964404}; Multi-pass membrane protein {ECO:0000305}. Note=The heterodimer with KCNK2 is detected at the astrocyte cell membrane. Not detected at the astrocyte cell membrane when KCNK2 is absent. Detected on neuronal cell bodies, and to a lesser degree on neuronal cell projections. Detected on hippocampus dentate gyrus granule cell bodies and to a lesser degree on proximal dendrites. Detected at the apical cell membrane in stria vascularis in the cochlea. Detected at the apical cell membrane of vestibular dark cells situated between the crista and the utricle in the inner ear. Detected at the apical cell membrane in kidney proximal tubule segment S1 and in subapical compartments in segments S1, S2 and S3. Predominantly in cytoplasmic structures in kidney distal convoluted tubules and collecting ducts (By similarity). Detected at the apical cell membrane of bronchial epithelial cells (PubMed:21964404). {ECO:0000250|UniProtKB:O08581, ECO:0000250|UniProtKB:Q9Z2T2, ECO:0000269|PubMed:21964404}.
uniprot
proteins
transmembrane_region
TRANSMEM 21..41; /note="Helical; Name=M1"; /evidence="ECO:0000269|PubMed:22282804, ECO:0007744|PDB:3UKM"; TRANSMEM 133..156; /note="Helical; Name=M2"; /evidence="ECO:0000269|PubMed:22282804, ECO:0007744|PDB:3UKM"; TRANSMEM 182..202; /note="Helical; Name=M3"; /evidence="ECO:0000269|PubMed:22282804, ECO:0007744|PDB:3UKM"; TRANSMEM 244..267; /note="Helical; Name=M4"; /evidence="ECO:0000269|PubMed:22282804, ECO:0007744|PDB:3UKM
uniprot
proteins