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Protein

Potassium channel subfamily K member 1

Gene

KCNK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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: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

Miscellaneous

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

Activity 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

Kineticsi

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

      Sites

      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

      • identical protein binding Source: IntAct
      • 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

      Keywordsi

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

      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
      Name:KCNK1
      Synonyms:HOHO11 Publication, KCNO1, TWIK1
      OrganismiHomo sapiens (Human)
      Taxonomic identifieri9606 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
      Proteomesi
      • UP000005640 Componenti: Chromosome 1

      Organism-specific databases

      EuPathDBiHostDB:ENSG00000135750.14
      HGNCiHGNC:6272 KCNK1
      MIMi601745 gene
      neXtProtiNX_O00180

      Subcellular locationi

      Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

      Topology

      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

      Keywords - Cellular componenti

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

      Pathology & Biotechi

      Mutagenesis

      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

      DisGeNETi3775
      OpenTargetsiENSG00000135750
      PharmGKBiPA219

      Chemistry databases

      DrugBankiDB00308 Ibutilide
      DB00908 Quinidine
      DB01346 Quinidine barbiturate

      Polymorphism and mutation databases

      BioMutaiKCNK1

      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

      EPDiO00180
      MaxQBiO00180
      PaxDbiO00180
      PeptideAtlasiO00180
      PRIDEiO00180
      ProteomicsDBi47763

      PTM databases

      iPTMnetiO00180
      PhosphoSitePlusiO00180

      Expressioni

      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

      BgeeiENSG00000135750 Expressed in 221 organ(s), highest expression level in cerebellum
      CleanExiHS_KCNK1
      ExpressionAtlasiO00180 baseline and differential
      GenevisibleiO00180 HS

      Organism-specific databases

      HPAiCAB022588
      HPA016049

      Interactioni

      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

      Binary interactionsi

      GO - Molecular functioni

      Protein-protein interaction databases

      BioGridi109976, 6 interactors
      DIPiDIP-59532N
      IntActiO00180, 10 interactors
      STRINGi9606.ENSP00000355580

      Structurei

      Secondary structure

      1336
      Legend: HelixTurnBeta strandPDB Structure known for this area
      Show more details

      3D structure databases

      ProteinModelPortaliO00180
      SMRiO00180
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Region

      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
      GeneTreeiENSGT00760000118858
      HOGENOMiHOG000286014
      HOVERGENiHBG052237
      InParanoidiO00180
      KOiK04912
      OMAiVQRVTIH
      OrthoDBiEOG091G0DIX
      PhylomeDBiO00180
      TreeFamiTF313947

      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
      PRINTSiPR01333 2POREKCHANEL
      PR01096 TWIK1CHANNEL
      PR01586 TWIKCHANNEL

      Sequence (1+)i

      Sequence statusi: Complete.

      This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

      O00180-1 [UniParc]FASTAAdd to basket
      « Hide
              10         20         30         40         50
      MLQSLAGSSC VRLVERHRSA WCFGFLVLGY LLYLVFGAVV FSSVELPYED
      60 70 80 90 100
      LLRQELRKLK RRFLEEHECL SEQQLEQFLG RVLEASNYGV SVLSNASGNW
      110 120 130 140 150
      NWDFTSALFF ASTVLSTTGY GHTVPLSDGG KAFCIIYSVI GIPFTLLFLT
      160 170 180 190 200
      AVVQRITVHV TRRPVLYFHI RWGFSKQVVA IVHAVLLGFV TVSCFFFIPA
      210 220 230 240 250
      AVFSVLEDDW NFLESFYFCF ISLSTIGLGD YVPGEGYNQK FRELYKIGIT
      260 270 280 290 300
      CYLLLGLIAM LVVLETFCEL HELKKFRKMF YVKKDKDEDQ VHIIEHDQLS
      310 320 330
      FSSITDQAAG MKEDQKQNEP FVATQSSACV DGPANH
      Length:336
      Mass (Da):38,143
      Last modified:July 1, 1997 - v1
      Checksum:i2A41D9501323215D
      GO

      Computationally mapped potential isoform sequencesi

      There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
      EntryEntry nameProtein names
      Gene namesLengthAnnotation
      Q5T5E6Q5T5E6_HUMAN
      Potassium channel subfamily K membe...
      KCNK1
      242Annotation score:

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      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
      CCDSiCCDS1599.1
      PIRiS65566
      RefSeqiNP_002236.1, NM_002245.3
      UniGeneiHs.208544

      Genome annotation databases

      EnsembliENST00000366621; ENSP00000355580; ENSG00000135750
      GeneIDi3775
      KEGGihsa:3775
      UCSCiuc010pxo.1 human

      Similar proteinsi

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      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
      CCDSiCCDS1599.1
      PIRiS65566
      RefSeqiNP_002236.1, NM_002245.3
      UniGeneiHs.208544

      3D structure databases

      Select the link destinations:
      PDBei
      RCSB PDBi
      PDBji
      Links Updated
      PDB entryMethodResolution (Å)ChainPositionsPDBsum
      3UKMX-ray3.40A/B/C/D19-288[»]
      ProteinModelPortaliO00180
      SMRiO00180
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi109976, 6 interactors
      DIPiDIP-59532N
      IntActiO00180, 10 interactors
      STRINGi9606.ENSP00000355580

      Chemistry databases

      DrugBankiDB00308 Ibutilide
      DB00908 Quinidine
      DB01346 Quinidine barbiturate

      PTM databases

      iPTMnetiO00180
      PhosphoSitePlusiO00180

      Polymorphism and mutation databases

      BioMutaiKCNK1

      Proteomic databases

      EPDiO00180
      MaxQBiO00180
      PaxDbiO00180
      PeptideAtlasiO00180
      PRIDEiO00180
      ProteomicsDBi47763

      Protocols and materials databases

      DNASUi3775
      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      EnsembliENST00000366621; ENSP00000355580; ENSG00000135750
      GeneIDi3775
      KEGGihsa:3775
      UCSCiuc010pxo.1 human

      Organism-specific databases

      CTDi3775
      DisGeNETi3775
      EuPathDBiHostDB:ENSG00000135750.14
      GeneCardsiKCNK1
      HGNCiHGNC:6272 KCNK1
      HPAiCAB022588
      HPA016049
      MIMi601745 gene
      neXtProtiNX_O00180
      OpenTargetsiENSG00000135750
      PharmGKBiPA219
      GenAtlasiSearch...

      Phylogenomic databases

      eggNOGiKOG1418 Eukaryota
      COG1226 LUCA
      GeneTreeiENSGT00760000118858
      HOGENOMiHOG000286014
      HOVERGENiHBG052237
      InParanoidiO00180
      KOiK04912
      OMAiVQRVTIH
      OrthoDBiEOG091G0DIX
      PhylomeDBiO00180
      TreeFamiTF313947

      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

      Miscellaneous databases

      ChiTaRSiKCNK1 human
      GeneWikiiKCNK1
      GenomeRNAii3775
      PROiPR:O00180
      SOURCEiSearch...

      Gene expression databases

      BgeeiENSG00000135750 Expressed in 221 organ(s), highest expression level in cerebellum
      CleanExiHS_KCNK1
      ExpressionAtlasiO00180 baseline and differential
      GenevisibleiO00180 HS

      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
      PRINTSiPR01333 2POREKCHANEL
      PR01096 TWIK1CHANNEL
      PR01586 TWIKCHANNEL
      ProtoNetiSearch...

      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: November 7, 2018
      This is version 169 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.

      Miscellaneousi

      Keywords - Technical termi

      3D-structure, Complete proteome, Reference proteome

      Documents

      1. SIMILARITY comments
        Index of protein domains and families
      2. Human chromosome 1
        Human chromosome 1: entries, gene names and cross-references to MIM
      3. MIM cross-references
        Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
      4. PDB cross-references
        Index of Protein Data Bank (PDB) cross-references
      UniProt is an ELIXIR core data resource
      Main funding by: National Institutes of Health

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