KCNK1 - Potassium channel subfamily K member 1 - human protein (Function)
 
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Gene
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KCNK1 »  Potassium channel subfamily K member 1
 
Protein also known as:  Inward rectifying potassium channel protein TWIK-1.
Gene name:  KCNK1
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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 (PubMed15820677, PubMed21653227). 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 (PubMed21653227, PubMed22431633). The homodimer has very low potassium channel activity, when expressed in heterologous systems, and can function as weakly inward rectifying potassium channel (PubMed8605869, PubMed8978667, PubMed15820677, PubMed21653227, PubMed22431633, PubMed23169818, PubMed25001086). 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 (PubMed23169818). Heterodimeric channels formed by KCNK1 and KCNK9 may contribute to halothane-sensitive currents (PubMed23169818). 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 (PubMed15820677, PubMed20498050, PubMed23169818). The low channel activity may be due to rapid internalization from the cell membrane and retention in recycling endosomes (PubMed19959478).  
14
  • UniProtKB
GO molecular function 
Inward rectifier potassium channel activitydefinition[GO:0005242]  
1
  • PINC
Potassium channel activitydefinition[GO:0005267]  
1
  • UniProtKB
Potassium ion leak channel activitydefinition[GO:0022841]  
2
  • UniProtKB
  • RefGenome
Sodium channel activitydefinition[GO:0005272]  
1
  • UniProtKB
Not  Voltage-gated potassium channel activitydefinition[GO:0005249]  
1
  • UniProtKB
GO biological process 
Potassium ion transmembrane transportdefinition[GO:0071805]  
2
  • UniProtKB
Potassium ion transportdefinition[GO:0006813]  
1
  • PINC
Regulation of resting membrane potentialdefinition[GO:0060075]  
1
  • UniProtKB
Sodium ion transmembrane transportdefinition[GO:0035725]  
1
  • UniProtKB
Stabilization of membrane potentialdefinition[GO:0030322]  
1
  • RefGenome
Enzymatic activity 
It is regulated in the following manner
Inhibited by Ba(2+) ions and quinidine (PubMed8605869). Inhibited by quinine (PubMed8605869, PubMed21653227). Is slightly inhibited by 10 mM tetraethylammonium (TEA), and only marginally inhibited by 4-aminopyridine, charybdotoxin and dendrotoxin (PubMed8605869). Lowering the extracellular pH to below 6.5 transiently activates the channel, and then inhibits channel activity (PubMed15820677, PubMed22431633). Inhibited when the intracellular pH is decreased down to pH 6.0, but this may be due to indirect effects (PubMed8605869).  
5
  • UniProtKB
Pathways 
According to Reactome, this protein belongs to the following pathway:
Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK)  R-HSA-1299308  
Note 
When the external K(+) concentration is lowered to subphysiological levels, it takes several minutes till the channel has reached a new, stable state characterized by increased Na(+) permeability (PubMed21653227). Likewise, when the external pH is lowered to values below 6.5, it takes several minutes till the channel has reached a new, stable state characterized by increased Na(+) permeability (PubMed22431633). When raising the K(+) concentration back to 5 mM, it takes 40 to 70 minutes for the channel to regain its original selectivity for K(+) (PubMed21653227). Likewise, it takes more that 25 minutes for the channel to regain its original K(+) selectivity when the pH is raised back to 7.4 (PubMed22431633).  
3
  • UniProtKB
 

Keywords

Biological process 
Ion transport  definition   [KW-0406]
Potassium transport  definition   [KW-0633]
Transport  definition   [KW-0813]
Molecular function 
Ion channel  definition   [KW-0407]
Potassium channel  definition   [KW-0631]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: KCNK1
GenomeRNAi: 3775
PRO: PR:O00180