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Potassium channel subfamily K member 1



Homo sapiens (Human)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


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).By similarity11 Publications


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 (PubMed:21653227). 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 (PubMed:22431633). 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+ (PubMed:21653227). 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 (PubMed:22431633).2 Publications

Enzyme regulationi

Inhibited by Ba2+ 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).4 Publications


Has a unit conductance of 34 pS. Both activation and channel closure are very rapid. Is not voltage-gated. The relationship between 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).2 Publications


      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Sitei118Important for increased permeability to Na(+) when K(+) levels are subphysiological1 Publication1
      Sitei146Part of a hydrophobic barrier that is stochastically dewetted and limits ion permeability2 Publications1
      Sitei261Part of a hydrophobic barrier that is stochastically dewetted and limits ion permeability1 Publication1

      GO - Molecular functioni

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

      GO - Biological processi

      • cardiac conduction Source: Reactome
      • potassium ion transmembrane transport Source: UniProtKB
      • potassium ion transport Source: ProtInc
      • regulation of resting membrane potential Source: UniProtKB
      • response to nicotine Source: Ensembl
      • sodium ion transmembrane transport Source: UniProtKB
      • stabilization of membrane potential Source: GO_Central


      Molecular functionIon channel, Potassium channel
      Biological processIon transport, Potassium transport, Transport

      Enzyme and pathway databases

      ReactomeiR-HSA-1299308. Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK).
      R-HSA-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-11 Publication
      Potassium channel K2P11 Publication
      Potassium channel KCNO1
      Gene namesi
      Synonyms:HOHO11 Publication, KCNO1, TWIK1
      OrganismiHomo sapiens (Human)
      Taxonomic identifieri9606 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
      • UP000005640 Componenti: Chromosome 1

      Organism-specific databases

      HGNCiHGNC:6272. KCNK1.

      Subcellular locationi


      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Topological domaini1 – 20Cytoplasmic1 PublicationAdd BLAST20
      Transmembranei21 – 41Helical1 PublicationAdd BLAST21
      Topological domaini42 – 103Extracellular1 Publication1 PublicationAdd BLAST62
      Intramembranei104 – 116Helical; Name=Pore helix 11 PublicationAdd BLAST13
      Intramembranei117 – 1221 Publication6
      Topological domaini123 – 132Extracellular1 Publication10
      Transmembranei133 – 156Helical1 PublicationAdd BLAST24
      Topological domaini157 – 181Cytoplasmic1 PublicationAdd BLAST25
      Transmembranei182 – 202Helical1 PublicationAdd BLAST21
      Topological domaini203 – 211Extracellular1 Publication9
      Intramembranei212 – 224Helical; Name=Pore helix 21 PublicationAdd BLAST13
      Intramembranei225 – 2311 Publication7
      Topological domaini232 – 243Extracellular1 PublicationAdd BLAST12
      Transmembranei244 – 267Helical1 PublicationAdd BLAST24
      Topological domaini268 – 336Cytoplasmic1 PublicationAdd BLAST69

      GO - Cellular componenti

      • apical plasma membrane Source: UniProtKB-SubCell
      • brush border membrane Source: Ensembl
      • cell junction Source: UniProtKB-KW
      • dendrite Source: UniProtKB-SubCell
      • integral component of membrane Source: UniProtKB
      • integral component of plasma membrane Source: UniProtKB
      • intracellular membrane-bounded organelle Source: HPA
      • inward rectifier potassium channel complex Source: Ensembl
      • perikaryon Source: UniProtKB-SubCell
      • plasma membrane Source: Reactome
      • potassium channel complex Source: UniProtKB
      • recycling endosome Source: UniProtKB-SubCell
      • synapse Source: UniProtKB-SubCell
      • voltage-gated potassium channel complex Source: ProtInc

      Keywords - Cellular componenti

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

      Pathology & Biotechi


      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Mutagenesisi69C → A: Abolishes channel activity and formation of disulfide-linked homodimers. 1 Publication1
      Mutagenesisi95N → A: Abolishes N-glycosylation. 1 Publication1
      Mutagenesisi108 – 109LF → FY: Impairs selectivity for K(+) ions and increases permeability to Na(+) ions, both at pH 7.4 and at pH 6. 1 Publication2
      Mutagenesisi118T → I: Abolishes change in ion selectivity in the presence of subphysiological K(+) levels. 1 Publication1
      Mutagenesisi122H → K: Increases channel activity, and has only a minor effect on the inhibition by acidification of the extracellular medium. 1 Publication1
      Mutagenesisi122H → N: Decreases channel activity and abolishes inhibition by acidification of the extracellular medium. 3 Publications1
      Mutagenesisi146L → A or V: Does not increase the low intrinsic channel activity. 1 Publication1
      Mutagenesisi146L → D: Increases channel activity. 2 Publications1
      Mutagenesisi146L → N or T: Increases channel activity. 1 Publication1
      Mutagenesisi146L → S: Increases channel activity. Strongly increases channel activity; when associated with S-261. 1 Publication1
      Mutagenesisi161T → A: No effect on channel activity. 1 Publication1
      Mutagenesisi228L → F: No effect on selectivity for K(+) ions. 1 Publication1
      Mutagenesisi231Y → 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. 1 Publication1
      Mutagenesisi250T → L: Slighly decreases the increased permeability to Na(+) ions at pH 6. 1 Publication1
      Mutagenesisi261L → D or N: Increases channel activity. 1 Publication1
      Mutagenesisi261L → S: Increases channel activity. Strongly increases channel activity; when associated with S-146. 1 Publication1
      Mutagenesisi274K → A, C, D, Q or R: Converts the electrically silent channel that is present at the cell membrane to an active channel. 1 Publication1
      Mutagenesisi274K → E: Converts the electrically silent channel that is present at the cell membrane to an active channel. No effect on retention in recycling endosomes. 6 Publications1
      Mutagenesisi293 – 294II → AA: Strongly increases location at the cell membrane. 1 Publication2
      Mutagenesisi299 – 336Missing : No effect on intracellular retention in recycling endosomes. 1 PublicationAdd BLAST38

      Organism-specific databases


      Chemistry databases

      DrugBankiDB00308. Ibutilide.
      DB00908. Quinidine.
      DB01346. Quinidine barbiturate.

      Polymorphism and mutation databases


      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      ChainiPRO_00001017401 – 336Potassium channel subfamily K member 1Add BLAST336

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Disulfide bondi69Interchain2 Publications
      Glycosylationi95N-linked (GlcNAc...) asparagine1 Publication1
      Cross-linki274Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)2 Publications
      Modified residuei326PhosphoserineBy similarity1

      Post-translational modificationi

      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).4 Publications

      Keywords - PTMi

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

      Proteomic databases


      PTM databases



      Tissue specificityi

      Detected in bronchial epithelial cells (PubMed:21964404). Detected in heart left atrium and left ventricle (PubMed:17478540). Detected in cardiac myocytes (at protein level) (PubMed:21653227). Widely expressed with high levels in heart, brain and kidney, and lower levels in colon, ovary, placenta, lung and liver (PubMed:8605869, PubMed:9362344). Highly expressed in cerebellum, and detected at lower levels in amygdala, caudate nucleus, brain cortex, hippocampus, putamen, substantia nigra, thalamus, dorsal root ganglion, spinal cord, pituitary, heart, kidney, lung, placenta, pancreas, stomach, small intestine, uterus and prostate (PubMed:11165377). Detected in right and left heart ventricle and atrium, and in heart Purkinje fibers (PubMed:17478540). Detected in bronchial epithelial cells (PubMed:21964404).6 Publications

      Gene expression databases

      ExpressionAtlasiO00180. baseline and differential.
      GenevisibleiO00180. HS.

      Organism-specific databases



      Subunit structurei

      Homodimer; disulfide-linked (PubMed:8978667, PubMed:22282804). 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 (PubMed:23169818). 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 (PubMed:15820677).By similarity4 Publications

      Protein-protein interaction databases

      BioGridi109976. 5 interactors.
      IntActiO00180. 3 interactors.


      Secondary structure

      Legend: HelixTurnBeta strandPDB Structure known for this area
      Show more details
      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Helixi19 – 66Combined sources48
      Helixi72 – 86Combined sources15
      Turni87 – 89Combined sources3
      Helixi104 – 115Combined sources12
      Helixi128 – 160Combined sources33
      Turni163 – 167Combined sources5
      Helixi177 – 195Combined sources19
      Helixi197 – 206Combined sources10
      Beta strandi207 – 209Combined sources3
      Helixi212 – 223Combined sources12
      Beta strandi236 – 238Combined sources3
      Helixi242 – 268Combined sources27
      Helixi271 – 278Combined sources8

      3D structure databases

      Select the link destinations:
      RCSB PDBi
      Links Updated
      PDB entryMethodResolution (Å)ChainPositionsPDBsum

      Family & Domainsi


      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Regioni117 – 122Selectivity filter 11 Publication1 Publication6
      Regioni225 – 230Selectivity filter 21 Publication6
      Regioni293 – 299Important for intracellular retention in recycling endosomes1 Publication7

      Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiKOG1418. Eukaryota.
      COG1226. LUCA.

      Family and domain databases

      InterProiView protein in InterPro
      IPR003280. 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.
      PfamiView protein in Pfam
      PF07885. Ion_trans_2. 2 hits.
      PIRSFiPIRSF038061. K_channel_subfamily_K_type. 1 hit.
      PR01096. TWIK1CHANNEL.
      PR01586. TWIKCHANNEL.


      Sequence statusi: Complete.

      O00180-1 [UniParc]FASTAAdd to basket

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      Mass (Da):38,143
      Last modified:July 1, 1997 - v1

      Sequence databases

      Select the link destinations:
      Links Updated
      U33632 mRNA. Translation: AAB01688.1.
      U76996 mRNA. Translation: AAB97878.1.
      U90065 mRNA. Translation: AAB51147.1.
      AL356357 Genomic DNA. No translation available.
      CH471098 Genomic DNA. Translation: EAW69989.1.
      BC018051 mRNA. Translation: AAH18051.1.
      RefSeqiNP_002236.1. NM_002245.3.

      Genome annotation databases

      EnsembliENST00000366621; ENSP00000355580; ENSG00000135750.
      UCSCiuc010pxo.1. human.

      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.

      Entry informationi

      Entry nameiKCNK1_HUMAN
      AccessioniPrimary (citable) accession number: O00180
      Secondary accession number(s): Q13307, Q5T5E8
      Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
      Last sequence update: July 1, 1997
      Last modified: July 5, 2017
      This is version 161 of the entry and version 1 of the sequence. See complete history.
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program
      DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.


      Keywords - Technical termi

      3D-structure, Complete proteome, Reference proteome


      1. Human chromosome 1
        Human chromosome 1: entries, gene names and cross-references to MIM
      2. MIM cross-references
        Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
      3. PDB cross-references
        Index of Protein Data Bank (PDB) cross-references
      4. SIMILARITY comments
        Index of protein domains and families