Names & Taxonomy

Uniprot ID:
O00180
Entry Name:
KCNK1_HUMAN
Status:
reviewed
Protein Names:
Potassium channel subfamily K member 1 (Inward rectifying potassium channel protein TWIK-1) (Potassium channel K2P1) (Potassium channel KCNO1)
Gene Names:
KCNK1 HOHO1 KCNO1 TWIK1
Gene Names Primary:
KCNK1
Organism:
Homo sapiens (Human)

Structure

Length:
336
Sequence:
MLQSLAGSSCVRLVERHRSAWCFGFLVLGYLLYLVFGAVVFSSVELPYEDLLRQELRKLKRRFLEEHECLSEQQLEQFLGRVLEASNYGVSVLSNASGNWNWDFTSALFFASTVLSTTGYGHTVPLSDGGKAFCIIYSVIGIPFTLLFLTAVVQRITVHVTRRPVLYFHIRWGFSKQVVAIVHAVLLGFVTVSCFFFIPAAVFSVLEDDWNFLESFYFCFISLSTIGLGDYVPGEGYNQKFRELYKIGITCYLLLGLIAMLVVLETFCELHELKKFRKMFYVKKDKDEDQVHIIEHDQLSFSSITDQAAGMKEDQKQNEPFVATQSSACVDGPANH
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane
Intramembrane:
INTRAMEM 104 116 Helical; Name=Pore helix 1.

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. 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:8605869, PubMed:8978667, PubMed:15820677, PubMed:21653227, PubMed:22431633, PubMed:23169818, PubMed:25001086). 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).
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: ; Kinetic parameters: Note=Has a unit conductance of 34 pS. Both activation and channel closure are very rapid. Is not voltage-gated. The relationship betweeen voltage and current is nearly linear. Has a mean open time of 0.3 msec at a membrane potential of -80 mV, and 1.9 msec at +80 mV (PubMed:8605869).
Enzyme Regulation:
ENZYME REGULATION: Inhibited by Ba(2+) ions and quinidine (PubMed:8605869). Inhibited by quinine (PubMed:8605869, PubMed:21653227). 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).
Cross Reference Drug Bank:
DB00308 DB00908 DB01346
Gene Ontology Go:
apical plasma membrane
brush border membrane
cell junction
cytoplasmic, membrane-bounded vesicle
dendrite
integral component of membrane
integral component of plasma membrane
inward rectifier potassium channel complex
perikaryon
plasma membrane
potassium channel complex
recycling endosome
synapse
voltage-gated potassium channel complex
inward rectifier potassium channel activity
potassium channel activity
potassium ion leak channel activity
sodium channel activity
cardiac conduction
potassium ion transmembrane transport
potassium ion transport
regulation of resting membrane potential
response to nicotine
sodium ion transmembrane transport
stabilization of membrane potential
synaptic transmission
Gene Ontology Biological Process:
cardiac conduction
potassium ion transmembrane transport
potassium ion transport
regulation of resting membrane potential
response to nicotine
sodium ion transmembrane transport
stabilization of membrane potential
synaptic transmission
Gene Ontology Molecular Function:
inward rectifier potassium channel activity
potassium channel activity
potassium ion leak channel activity
sodium channel activity
Gene Ontology Cellular Component:
apical plasma membrane
brush border membrane
cell junction
cytoplasmic, membrane-bounded vesicle
dendrite
integral component of membrane
integral component of plasma membrane
inward rectifier potassium channel complex
perikaryon
plasma membrane
potassium channel complex
recycling endosome
synapse
voltage-gated potassium channel complex
Keywords:
3D-structure
Cell junction
Cell membrane
Cell projection
Complete proteome
Cytoplasmic vesicle
Disulfide bond
Endosome
Glycoprotein
Ion channel
Ion transport
Isopeptide bond
Membrane
Phosphoprotein
Potassium
Potassium channel
Potassium transport
Reference proteome
Synapse
Transmembrane
Transmembrane helix
Transport
Ubl conjugation

Publication

PubMed ID:
8605869 9462864 9362344 16710414 15489334 8978667 11165377 15820677 17693262 17478540 19959478 20498050 21653227 21964404 22814378 22431633 23169818 25530075 25001086 25339226 22282804