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Protein

Potassium channel subfamily K member 1

Gene

Kcnk1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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:17452494, PubMed:19571146). 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:22948150). The homodimer has very low potassium channel activity, when expressed in heterologous systems, and can function as weakly inward rectifying potassium channel. Channel activity is modulated by activation of serotonin receptors (PubMed:17452494). 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. Heterodimeric channels formed by KCNK1 and KCNK9 may contribute to halothane-sensitive currents (By similarity). 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). Contributes to the regulation of the resting membrane potential of pancreatic beta cells (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). The low channel activity of homodimeric KCNK1 may be due to sumoylation. The low channel activity may be due to rapid internalization from the cell membrane and retention in recycling endosomes (By similarity).By similarity3 Publications

Enzyme regulationi

Inhibited by 100 µM quinine. Slightly inhibited by Ba+ (PubMed:17452494). Activity is first increased and then decreased when the extracellular pH is lowered to 6.0 (PubMed:17452494, PubMed:22948150).2 Publications

Kineticsi

Both activation and channel closure are very rapid. Is not voltage-gated (PubMed:19571146). The relationship betweeen voltage and current is nearly linear (PubMed:19571146).By similarity

Curated1 Publication

      Sites

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Sitei118 – 1181Important for increased permeability to Na(+) when K(+) levels are subphysiologicalBy similarity
      Sitei146 – 1461Part of a hydrophobic barrier that is stochastically dewetted and limits ion permeabilityBy similarity
      Sitei261 – 2611Part of a hydrophobic barrier that is stochastically dewetted and limits ion permeabilityBy similarity

      GO - Molecular functioni

      GO - Biological processi

      Complete GO annotation...

      Keywords - Molecular functioni

      Ion channel, Potassium channel

      Keywords - Biological processi

      Ion transport, Potassium transport, Transport

      Keywords - Ligandi

      Potassium

      Enzyme and pathway databases

      ReactomeiR-RNO-1299308. Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK).
      R-RNO-5576886. Phase 4 - resting membrane potential.

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Potassium channel subfamily K member 1
      Alternative name(s):
      Inward rectifying potassium channel protein TWIK-1
      Short name:
      rTWIK
      Potassium channel K2P11 Publication
      Gene namesi
      Name:Kcnk1Imported
      OrganismiRattus norvegicus (Rat)
      Taxonomic identifieri10116 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
      Proteomesi
      • UP000002494 Componenti: Chromosome 19

      Organism-specific databases

      RGDi621447. Kcnk1.

      Subcellular locationi

      Topology

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Topological domaini1 – 2020CytoplasmicBy similarityAdd
      BLAST
      Transmembranei21 – 4121HelicalBy similarityAdd
      BLAST
      Topological domaini42 – 10362ExtracellularBy similarityAdd
      BLAST
      Intramembranei104 – 11613Helical; Name=Pore helix 1By similarityAdd
      BLAST
      Intramembranei117 – 1226By similarity
      Topological domaini123 – 13210ExtracellularBy similarity
      Transmembranei133 – 15624HelicalBy similarityAdd
      BLAST
      Topological domaini157 – 18125CytoplasmicBy similarityAdd
      BLAST
      Transmembranei182 – 20221HelicalBy similarityAdd
      BLAST
      Topological domaini203 – 2119ExtracellularBy similarity
      Intramembranei212 – 22413Helical; Name=Pore helix 2By similarityAdd
      BLAST
      Intramembranei225 – 2317By similarity
      Topological domaini232 – 24312ExtracellularBy similarityAdd
      BLAST
      Transmembranei244 – 26724HelicalBy similarityAdd
      BLAST
      Topological domaini268 – 33669CytoplasmicBy similarityAdd
      BLAST

      GO - Cellular componenti

      • apical plasma membrane Source: RGD
      • brush border membrane Source: RGD
      • cell junction Source: UniProtKB-KW
      • cytoplasm Source: RGD
      • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
      • dendrite Source: UniProtKB-SubCell
      • integral component of membrane Source: UniProtKB
      • integral component of plasma membrane Source: UniProtKB
      • inward rectifier potassium channel complex Source: Ensembl
      • perikaryon Source: UniProtKB-SubCell
      • potassium channel complex Source: UniProtKB
      • recycling endosome Source: UniProtKB-SubCell
      • synapse Source: UniProtKB-SubCell
      Complete GO annotation...

      Keywords - Cellular componenti

      Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Endosome, Membrane, Synapse

      Pathology & Biotechi

      Mutagenesis

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Mutagenesisi274 – 2741K → E: Strongly increases channel activity. 2 Publications

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Chaini1 – 336336Potassium channel subfamily K member 1PRO_0000299071Add
      BLAST

      Amino acid modifications

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Disulfide bondi69 – 69InterchainBy similarity
      Glycosylationi95 – 951N-linked (GlcNAc...)Sequence analysis
      Cross-linki274 – 274Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
      Modified residuei326 – 3261PhosphoserineCombined sources

      Post-translational modificationi

      Sumoylation is controversial. Sumoylated by UBE2I. Not sumoylated when expressed in xenopus oocytes or mammalian cells. Sumoylation inactivates the channel, but does not interfere with expression at the cell membrane. Sumoylation of a single subunit is sufficient to silence the dimeric channel. Sumoylation of KCNK1 is sufficient to silence heterodimeric channels formed by KCNK1 and KCNK3 or KCNK9. Desumoylated by SENP1; this activates the channel. Desumoylated by SENP1; this strongly increases halothane-mediated activation of heterodimeric channels formed with KCNK9. SENP1 treatment has no effect.By similarity

      Keywords - PTMi

      Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

      Proteomic databases

      PaxDbiQ9Z2T2.

      PTM databases

      iPTMnetiQ9Z2T2.
      PhosphoSiteiQ9Z2T2.

      Expressioni

      Tissue specificityi

      Detected in brain and in kidney cortex and medulla, especially at the renal brush border membranes of the proximal convoluted tubules, in distal tubules and on intercalated cells of the collecting duct (PubMed:9843722). Detected cerebellum granule neurons (PubMed:25305496). Detected in astrocytes in hippocampus stratum radiatum (PubMed:19571146). Highly expressed in the stria vascularis in the cochlea (PubMed:12855359). Detected in neurons in Scarpa's ganglion in the inner ear, at nerve terminals in the crista ampullaris, in supporting cells and dark cells, but not in hair cells (PubMed:18838117) (at protein level). Detected in the brain cerebellar granule cell layer, amygdala, thalamus reticular nucleus, habenula, mesencephalic trigeminal neurons, neocortex and piriform cortex, and at lower levels in the olfactory bulb (PubMed:11567039). Detected cerebellum granule neurons (PubMed:23169818, PubMed:25305496). Detected in Scarpa's ganglia and crista ampullaris in the inner ear (PubMed:18838117).7 Publications

      Gene expression databases

      BgeeiENSRNOG00000019937.
      GenevisibleiQ9Z2T2. RN.

      Interactioni

      Subunit structurei

      Homodimer; disulfide-linked (PubMed:9843722). Heterodimer with KCNK2; disulfide-linked (By similarity). In astrocytes, forms mostly heterodimeric potassium channels with KCNK2, with only a minor proportion of functional channels containing homodimeric KCNK1 (By similarity). Interacts with KCNK3 and KCNK9, forming functional heterodimeric channels (By similarity). Interacts with GNG4 (By similarity). Identified in a complex with PSD and ARF6; interacts only with PSD that is bound to ARF6 (By similarity). Interacts with UBE2I (By similarity).By similarity1 Publication

      Protein-protein interaction databases

      STRINGi10116.ENSRNOP00000027058.

      Structurei

      3D structure databases

      ProteinModelPortaliQ9Z2T2.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Region

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Regioni117 – 1226Selectivity filter 1By similarity
      Regioni225 – 2306Selectivity filter 2By similarity
      Regioni293 – 2997Important for intracellular retention in recycling endosomesBy similarity

      Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiKOG1418. Eukaryota.
      COG1226. LUCA.
      GeneTreeiENSGT00760000118858.
      HOGENOMiHOG000286014.
      HOVERGENiHBG052237.
      InParanoidiQ9Z2T2.
      KOiK04912.
      OMAiKQLRKMF.
      PhylomeDBiQ9Z2T2.
      TreeFamiTF313947.

      Family and domain databases

      InterProiIPR003280. 2pore_dom_K_chnl.
      IPR003092. 2pore_dom_K_chnl_TASK.
      IPR005408. 2pore_dom_K_chnl_TWIK.
      IPR001779. 2pore_dom_K_chnl_TWIK1.
      IPR013099. K_chnl_dom.
      [Graphical view]
      PfamiPF07885. Ion_trans_2. 2 hits.
      [Graphical view]
      PIRSFiPIRSF038061. K_channel_subfamily_K_type. 1 hit.
      PRINTSiPR01333. 2POREKCHANEL.
      PR01096. TWIK1CHANNEL.
      PR01586. TWIKCHANNEL.

      Sequencei

      Sequence statusi: Complete.

      Q9Z2T2-1 [UniParc]FASTAAdd to basket

      « Hide

              10         20         30         40         50
      MLQSLAGSSC VRLVERHRSA WCFGFLVLGY LLYLVFGAVV FSSVELPYED
      60 70 80 90 100
      LLRQELRKLK RRFLEEHECL SEPQLEQFLG RVLEASNYGV SVLSNASGNW
      110 120 130 140 150
      NWDFTSALFF ASTVLSTTGY GHTVPLSDGG KAFCIIYSVI GIPFTLLFLT
      160 170 180 190 200
      AVVQRVTVHV TRRPVLYFHI RWGFSKQVVA IVHAVLLGFV TVSCFFFIPA
      210 220 230 240 250
      AVFSVLEDDW NFLESFYFCF ISLSTIGLGD YVPGEGYNQK FRELYKIGIT
      260 270 280 290 300
      CYLLLGLIAM LVVLETFCEL HELKKFRKMF YVKKDKDEDQ VHIMEHDQLS
      310 320 330
      FSSITEQAAG LKEEQKQNEP FVASQSPPYE DGSANH
      Length:336
      Mass (Da):38,228
      Last modified:May 1, 1999 - v1
      Checksum:i5E78031947D75DE6
      GO

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      AF022819 mRNA. Translation: AAD09336.1.
      BC061807 mRNA. Translation: AAH61807.1.
      RefSeqiNP_067720.1. NM_021688.3.
      UniGeneiRn.15693.

      Genome annotation databases

      EnsembliENSRNOT00000027058; ENSRNOP00000027058; ENSRNOG00000019937.
      ENSRNOT00000088626; ENSRNOP00000070146; ENSRNOG00000019937.
      GeneIDi59324.
      KEGGirno:59324.
      UCSCiRGD:621447. rat.

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      AF022819 mRNA. Translation: AAD09336.1.
      BC061807 mRNA. Translation: AAH61807.1.
      RefSeqiNP_067720.1. NM_021688.3.
      UniGeneiRn.15693.

      3D structure databases

      ProteinModelPortaliQ9Z2T2.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      STRINGi10116.ENSRNOP00000027058.

      PTM databases

      iPTMnetiQ9Z2T2.
      PhosphoSiteiQ9Z2T2.

      Proteomic databases

      PaxDbiQ9Z2T2.

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      EnsembliENSRNOT00000027058; ENSRNOP00000027058; ENSRNOG00000019937.
      ENSRNOT00000088626; ENSRNOP00000070146; ENSRNOG00000019937.
      GeneIDi59324.
      KEGGirno:59324.
      UCSCiRGD:621447. rat.

      Organism-specific databases

      CTDi3775.
      RGDi621447. Kcnk1.

      Phylogenomic databases

      eggNOGiKOG1418. Eukaryota.
      COG1226. LUCA.
      GeneTreeiENSGT00760000118858.
      HOGENOMiHOG000286014.
      HOVERGENiHBG052237.
      InParanoidiQ9Z2T2.
      KOiK04912.
      OMAiKQLRKMF.
      PhylomeDBiQ9Z2T2.
      TreeFamiTF313947.

      Enzyme and pathway databases

      ReactomeiR-RNO-1299308. Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK).
      R-RNO-5576886. Phase 4 - resting membrane potential.

      Miscellaneous databases

      PROiQ9Z2T2.

      Gene expression databases

      BgeeiENSRNOG00000019937.
      GenevisibleiQ9Z2T2. RN.

      Family and domain databases

      InterProiIPR003280. 2pore_dom_K_chnl.
      IPR003092. 2pore_dom_K_chnl_TASK.
      IPR005408. 2pore_dom_K_chnl_TWIK.
      IPR001779. 2pore_dom_K_chnl_TWIK1.
      IPR013099. K_chnl_dom.
      [Graphical view]
      PfamiPF07885. Ion_trans_2. 2 hits.
      [Graphical view]
      PIRSFiPIRSF038061. K_channel_subfamily_K_type. 1 hit.
      PRINTSiPR01333. 2POREKCHANEL.
      PR01096. TWIK1CHANNEL.
      PR01586. TWIKCHANNEL.
      ProtoNetiSearch...

      Entry informationi

      Entry nameiKCNK1_RAT
      AccessioniPrimary (citable) accession number: Q9Z2T2
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: August 21, 2007
      Last sequence update: May 1, 1999
      Last modified: September 7, 2016
      This is version 105 of the entry and version 1 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program

      Miscellaneousi

      Miscellaneous

      When the external pH is lowered, it takes about 8 minutes till the channel has reached a new, stable state characterized by increased Na+ permeability. Likewise, when raising the pH back to 7.4, it takes about 12 minutes for the channel to regain its original selectivity for K+.1 Publication

      Keywords - Technical termi

      Complete proteome, Reference proteome

      Documents

      1. SIMILARITY comments
        Index of protein domains and families

      Similar proteinsi

      Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
      100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
      90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
      50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.