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Protein

Potassium channel subfamily K member 1

Gene

Kcnk1

Organism
Mus musculus (Mouse)
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:16847696, PubMed:22431633, PubMed:24368895). 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. The homodimer has very low potassium channel activity, when expressed in heterologous systems, and can function as weakly inward rectifying potassium channel (PubMed:9013852, PubMed:24496152). Channel activity is modulated by activation of serotonin receptors (PubMed:24368895). Heterodimeric channels containing KCNK1 and KCNK2 have much higher activity, and may represent the predominant form in astrocytes (PubMed:24496152). 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 (PubMed:25406588). Contributes to the regulation of action potential firing in dentate gyrus granule cells and down-regulates their intrinsic excitability (PubMed:25406588). 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 (PubMed:24496152). Required for normal ion and water transport in the kidney (PubMed:16025300). Contributes to the regulation of the resting membrane potential of pancreatic beta cells (PubMed:22431633). 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 (PubMed:15540117).By similarity7 Publications

Enzyme regulationi

Inhibited by quinine, quinidine, barium, and internal acidification.1 Publication1 Publication

Kineticsi

Both activation and channel closure are very rapid. Is not voltage-gated (PubMed:22431633, PubMed:24496152). The relationship between voltage and current is nearly linear (PubMed:22431633, PubMed:24496152).Curated2 Publications

Manual assertion based on experiment ini

      Sites

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Sitei118Important for increased permeability to Na(+) when K(+) levels are subphysiologicalBy similarity1
      Sitei146Part of a hydrophobic barrier that is stochastically dewetted and limits ion permeabilityBy similarity1
      Sitei261Part of a hydrophobic barrier that is stochastically dewetted and limits ion permeabilityBy similarity1

      GO - Molecular functioni

      • inward rectifier potassium channel activity Source: UniProtKB
      • potassium channel activity Source: MGI
      • potassium ion leak channel activity Source: UniProtKB
      • sodium channel activity Source: UniProtKB

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

      Protein family/group databases

      TCDBi1.A.1.8.1. the voltage-gated ion channel (vic) superfamily.

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Potassium channel subfamily K member 1
      Alternative name(s):
      Inward rectifying potassium channel protein TWIK-11 Publication
      Gene namesi
      Name:Kcnk1
      OrganismiMus musculus (Mouse)
      Taxonomic identifieri10090 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
      Proteomesi
      • UP000000589 Componenti: Chromosome 8

      Organism-specific databases

      MGIiMGI:109322. Kcnk1.

      Subcellular locationi

      Topology

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Topological domaini1 – 20CytoplasmicBy similarityAdd BLAST20
      Transmembranei21 – 41HelicalBy similarityAdd BLAST21
      Topological domaini42 – 103ExtracellularBy similarityAdd BLAST62
      Intramembranei104 – 116Helical; Name=Pore helix 1By similarityAdd BLAST13
      Intramembranei117 – 122By similarity6
      Topological domaini123 – 132ExtracellularBy similarity10
      Transmembranei133 – 156HelicalBy similarityAdd BLAST24
      Topological domaini157 – 181CytoplasmicBy similarityAdd BLAST25
      Transmembranei182 – 202HelicalBy similarityAdd BLAST21
      Topological domaini203 – 211ExtracellularBy similarity9
      Intramembranei212 – 224Helical; Name=Pore helix 2By similarityAdd BLAST13
      Intramembranei225 – 231By similarity7
      Topological domaini232 – 243ExtracellularBy similarityAdd BLAST12
      Transmembranei244 – 267HelicalBy similarityAdd BLAST24
      Topological domaini268 – 336CytoplasmicBy similarityAdd BLAST69

      GO - Cellular componenti

      • apical plasma membrane Source: UniProtKB-SubCell
      • brush border membrane Source: Ensembl
      • cell junction Source: UniProtKB-KW
      • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
      • dendrite Source: UniProtKB-SubCell
      • endosome Source: MGI
      • integral component of membrane Source: UniProtKB
      • integral component of plasma membrane Source: UniProtKB
      • inward rectifier potassium channel complex Source: UniProtKB
      • 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

      Disruption phenotypei

      No visible phenotype on standard chow, excepting a lower urinary flow rate (PubMed:16025300). Mice appear normal and are fertile (PubMed:24368895). When kept on a low phosphate diet, both wild-type and mutant mice show strongly reduced urinary phosphate secretion. Still, mutant mice display higher fractional urinary phosphate secretion relative to wild-type, leading to reduced inorganic phosphate levels in blood plasma. The impaired phosphate homeostasis seems to be due to indirect effects on the expression of other transporters, such as SLC34A1 and AQP2 (PubMed:16025300). Principal cells from kidney collecting duct are hyperpolarized, display reduced potassium conductance and strongly reduced quinidine-sensitive potassium channel activity (PubMed:16847696). Besides, collecting ducts from mutant mouse kidney display a larger diameter relative to wild-type (PubMed:16847696).3 Publications

      Mutagenesis

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Mutagenesisi69C → S: Abolishes formation of a disulfide-linked heterodimer with KCNK2. 1 Publication1
      Mutagenesisi119G → E: Abolishes potassium channel activity. 1 Publication1
      Mutagenesisi293 – 294IM → AA: Increases channel expression at the cell membrane, resulting in higher channel activity. 1 Publication2

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      ChainiPRO_00001017411 – 336Potassium channel subfamily K member 1Add BLAST336

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Disulfide bondi69InterchainBy similarity1 Publication
      Glycosylationi95N-linked (GlcNAc...)Sequence analysis1
      Cross-linki274Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
      Modified residuei326PhosphoserineBy similarity1

      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

      MaxQBiO08581.
      PaxDbiO08581.
      PeptideAtlasiO08581.
      PRIDEiO08581.

      PTM databases

      iPTMnetiO08581.
      PhosphoSitePlusiO08581.

      Expressioni

      Tissue specificityi

      Detected in spiral ganglion neurons (PubMed:17079103). Detected in hippocampus CA1 and CA1 regions and in the molecular layer of the dentate gyrus (PubMed:24368895, PubMed:25406588). Detected on hippocampus astrocytes (PubMed:24368895, PubMed:24496152). Highly expressed in the stria vascularis in the cochlea (PubMed:12855359). Detected in pancreas islet beta cells (PubMed:22431633). Detected in kidney, at brush border membranes in proximal tubules and in cytoplasmic structures in distal convoluted tubules, thick ascending limbs and collecting ducts (at protein level) (PubMed:15540117, PubMed:16025300). Widely expressed. Detected in spiral ganglion cells (PubMed:17079103). Highest expression in brain, kidney, thyroid, salivary gland, adrenal gland, prostate, epididymis, uterus, placenta, colon and jejunum. Moderate expression in eyes, pituitary, pancreas, smooth muscle, testis and ovary. Very low levels in lung, aorta, liver, heart, skeletal muscle, thymus and spleen. In the brain, highest expression in cerebellar granule cells, brainstem, hippocampus and cerebral cortex (PubMed:18222039).8 Publications

      Developmental stagei

      Detected at very low levels in the embyonic central nervous system (PubMed:9559671, PubMed:18222039). Detected as early as 7 days post conception (PubMed:9559671). Detected in dorsal root ganglia, hippocampus, olfactory epithelia and intestine at 19 dpc (PubMed:18222039). Expression in the brain increases strongly 3-8 days after birth, a period of intense postnatal brain development (PubMed:9559671, PubMed:18222039). Detected in dentate granule cells; expression levels show no significant variability during postnatal development (PubMed:18222039). Expression is higher in adults than in neonates (PubMed:9559671, PubMed:18222039).2 Publications

      Gene expression databases

      BgeeiENSMUSG00000033998.
      CleanExiMM_KCNK1.
      GenevisibleiO08581. MM.

      Interactioni

      Subunit structurei

      Homodimer; disulfide-linked (PubMed:9013852). Heterodimer with KCNK2; disulfide-linked (PubMed:24496152). 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 (PubMed:24496152). Identified in a complex with PSD and ARF6; interacts only with PSD that is bound to ARF6 (PubMed:15540117). Interacts with UBE2I (By similarity).By similarity3 Publications

      Protein-protein interaction databases

      BioGridi200907. 46 interactors.
      IntActiO08581. 45 interactors.
      STRINGi10090.ENSMUSP00000046103.

      Structurei

      3D structure databases

      ProteinModelPortaliO08581.
      SMRiO08581.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Region

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Regioni117 – 122Selectivity filter 1By similarity6
      Regioni225 – 230Selectivity filter 2By similarity6
      Regioni293 – 299Important for intracellular retention in recycling endosomesBy similarity7

      Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiKOG1418. Eukaryota.
      COG1226. LUCA.
      GeneTreeiENSGT00760000118858.
      HOGENOMiHOG000286014.
      HOVERGENiHBG052237.
      InParanoidiO08581.
      KOiK04912.
      OMAiKQLRKMF.
      OrthoDBiEOG091G0DIX.
      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.

      O08581-1 [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 YVKKDKDEDL VHIMEHDQLS
      310 320 330
      FSSVTEQVAG LKEEQKQSEP FVASQSPPYE DGSADH
      Length:336
      Mass (Da):38,201
      Last modified:July 27, 2011 - v2
      Checksum:i76B7FD5361A6216C
      GO

      Experimental Info

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Sequence conflicti44V → E in AAC16973 (PubMed:9013852).Curated1
      Sequence conflicti152V → L in AAC16973 (PubMed:9013852).Curated1
      Sequence conflicti259A → T in AAC16973 (PubMed:9013852).Curated1

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      AF033017 mRNA. Translation: AAC16973.1.
      CH466525 Genomic DNA. Translation: EDL11808.1.
      BC003729 mRNA. Translation: AAH03729.1.
      CCDSiCCDS22783.1.
      RefSeqiNP_032456.2. NM_008430.2.
      UniGeneiMm.10800.

      Genome annotation databases

      EnsembliENSMUST00000046765; ENSMUSP00000046103; ENSMUSG00000033998.
      GeneIDi16525.
      KEGGimmu:16525.
      UCSCiuc009nyr.3. mouse.

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      AF033017 mRNA. Translation: AAC16973.1.
      CH466525 Genomic DNA. Translation: EDL11808.1.
      BC003729 mRNA. Translation: AAH03729.1.
      CCDSiCCDS22783.1.
      RefSeqiNP_032456.2. NM_008430.2.
      UniGeneiMm.10800.

      3D structure databases

      ProteinModelPortaliO08581.
      SMRiO08581.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi200907. 46 interactors.
      IntActiO08581. 45 interactors.
      STRINGi10090.ENSMUSP00000046103.

      Protein family/group databases

      TCDBi1.A.1.8.1. the voltage-gated ion channel (vic) superfamily.

      PTM databases

      iPTMnetiO08581.
      PhosphoSitePlusiO08581.

      Proteomic databases

      MaxQBiO08581.
      PaxDbiO08581.
      PeptideAtlasiO08581.
      PRIDEiO08581.

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      EnsembliENSMUST00000046765; ENSMUSP00000046103; ENSMUSG00000033998.
      GeneIDi16525.
      KEGGimmu:16525.
      UCSCiuc009nyr.3. mouse.

      Organism-specific databases

      CTDi3775.
      MGIiMGI:109322. Kcnk1.

      Phylogenomic databases

      eggNOGiKOG1418. Eukaryota.
      COG1226. LUCA.
      GeneTreeiENSGT00760000118858.
      HOGENOMiHOG000286014.
      HOVERGENiHBG052237.
      InParanoidiO08581.
      KOiK04912.
      OMAiKQLRKMF.
      OrthoDBiEOG091G0DIX.
      TreeFamiTF313947.

      Enzyme and pathway databases

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

      Miscellaneous databases

      ChiTaRSiKcnk1. mouse.
      PROiO08581.
      SOURCEiSearch...

      Gene expression databases

      BgeeiENSMUSG00000033998.
      CleanExiMM_KCNK1.
      GenevisibleiO08581. MM.

      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_MOUSE
      AccessioniPrimary (citable) accession number: O08581
      Secondary accession number(s): Q99L99
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: February 21, 2001
      Last sequence update: July 27, 2011
      Last modified: November 30, 2016
      This is version 141 of the entry and version 2 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program

      Miscellaneousi

      Keywords - Technical termi

      Complete proteome, Reference proteome

      Documents

      1. MGD cross-references
        Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
      2. 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.