Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Potassium channel subfamily K member 1

Gene

KCNK1

Organism
Homo sapiens (Human)
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: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

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

Kineticsi

Has a unit conductance of 34 pS. Both activation and channel closure are very rapid. Is not voltage-gated. The relationship betweeen 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)LengthDescriptionGraphical viewFeature identifierActions
      Sitei118 – 1181Important for increased permeability to Na(+) when K(+) levels are subphysiological1 Publication
      Sitei146 – 1461Part of a hydrophobic barrier that is stochastically dewetted and limits ion permeability2 Publications
      Sitei261 – 2611Part of a hydrophobic barrier that is stochastically dewetted and limits ion permeability1 Publication

      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

      • potassium ion transmembrane transport Source: UniProtKB
      • potassium ion transport Source: ProtInc
      • regulation of resting membrane potential Source: UniProtKB
      • sodium ion transmembrane transport Source: UniProtKB
      • stabilization of membrane potential Source: GO_Central
      • synaptic transmission Source: Reactome
      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

      ReactomeiREACT_75779. Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK).

      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
      ProteomesiUP000005640 Componenti: Chromosome 1

      Organism-specific databases

      HGNCiHGNC:6272. KCNK1.

      Subcellular locationi

      Topology

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Topological domaini1 – 2020Cytoplasmic1 PublicationAdd
      BLAST
      Transmembranei21 – 4121Helical1 PublicationAdd
      BLAST
      Topological domaini42 – 10362Extracellular1 Publication1 PublicationAdd
      BLAST
      Intramembranei104 – 11613Helical; Name=Pore helix 11 PublicationAdd
      BLAST
      Intramembranei117 – 12261 Publication
      Topological domaini123 – 13210Extracellular1 Publication
      Transmembranei133 – 15624Helical1 PublicationAdd
      BLAST
      Topological domaini157 – 18125Cytoplasmic1 PublicationAdd
      BLAST
      Transmembranei182 – 20221Helical1 PublicationAdd
      BLAST
      Topological domaini203 – 2119Extracellular1 Publication
      Intramembranei212 – 22413Helical; Name=Pore helix 21 PublicationAdd
      BLAST
      Intramembranei225 – 23171 Publication
      Topological domaini232 – 24312Extracellular1 PublicationAdd
      BLAST
      Transmembranei244 – 26724Helical1 PublicationAdd
      BLAST
      Topological domaini268 – 33669Cytoplasmic1 PublicationAdd
      BLAST

      GO - Cellular componenti

      • endosome Source: Ensembl
      • integral component of membrane Source: UniProtKB
      • integral component of plasma membrane Source: UniProtKB
      • inward rectifier potassium channel complex Source: Ensembl
      • plasma membrane Source: Reactome
      • potassium channel complex Source: UniProtKB
      • voltage-gated potassium channel complex Source: ProtInc
      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
      Mutagenesisi69 – 691C → A: Abolishes channel activity and formation of disulfide-linked homodimers. 1 Publication
      Mutagenesisi95 – 951N → A: Abolishes N-glycosylation. 1 Publication
      Mutagenesisi108 – 1092LF → FY: Impairs selectivity for K(+) ions and increases permeability to Na(+) ions, both at pH 7.4 and at pH 6. 1 Publication
      Mutagenesisi118 – 1181T → I: Abolishes change in ion selectivity in the presence of subphysiological K(+) levels. 1 Publication
      Mutagenesisi122 – 1221H → K: Increases channel activity, and has only a minor effect on the inhibition by acidification of the extracellular medium. 1 Publication
      Mutagenesisi122 – 1221H → N: Decreases channel activity and abolishes inhibition by acidification of the extracellular medium. 3 Publications
      Mutagenesisi146 – 1461L → A or V: Does not increase the low intrinsic channel activity. 1 Publication
      Mutagenesisi146 – 1461L → D: Increases channel activity. 2 Publications
      Mutagenesisi146 – 1461L → N or T: Increases channel activity. 1 Publication
      Mutagenesisi146 – 1461L → S: Increases channel activity. Strongly increases channel activity; when associated with S-261. 1 Publication
      Mutagenesisi161 – 1611T → A: No effect on channel activity. 1 Publication
      Mutagenesisi228 – 2281L → F: No effect on selectivity for K(+) ions. 1 Publication
      Mutagenesisi231 – 2311Y → F: Strongly decreases activity of homodimeric channels and of heterodimeric channels formed with KCNK3 and with KCNK9. No effect on location at the cell mebrane. 1 Publication
      Mutagenesisi250 – 2501T → L: Slighly decreases the increased permeability to Na(+) ions at pH 6. 1 Publication
      Mutagenesisi261 – 2611L → D or N: Increases channel activity. 1 Publication
      Mutagenesisi261 – 2611L → S: Increases channel activity. Strongly increases channel activity; when associated with S-146. 1 Publication
      Mutagenesisi274 – 2741K → A, C, D, Q or R: Converts the electrically silent channel that is present at the cell membrane to an active channel. 1 Publication
      Mutagenesisi274 – 2741K → 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 Publications
      Mutagenesisi293 – 2942II → AA: Strongly increases location at the cell membrane. 1 Publication
      Mutagenesisi299 – 33638Missing : No effect on intracellular retention in recycling endosomes. 1 PublicationAdd
      BLAST

      Organism-specific databases

      PharmGKBiPA219.

      Chemistry

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

      Polymorphism and mutation databases

      BioMutaiKCNK1.

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Chaini1 – 336336Potassium channel subfamily K member 1PRO_0000101740Add
      BLAST

      Amino acid modifications

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Disulfide bondi69 – 69Interchain2 Publications
      Glycosylationi95 – 951N-linked (GlcNAc...)1 Publication
      Cross-linki274 – 274Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication

      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 c 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, Ubl conjugation

      Proteomic databases

      MaxQBiO00180.
      PaxDbiO00180.
      PRIDEiO00180.

      PTM databases

      PhosphoSiteiO00180.

      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

      BgeeiO00180.
      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

      Protein-protein interaction databases

      BioGridi109976. 4 interactions.
      DIPiDIP-59532N.
      IntActiO00180. 1 interaction.
      STRINGi9606.ENSP00000355580.

      Structurei

      Secondary structure

      1
      336
      Legend: HelixTurnBeta strand
      Show more details
      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Helixi19 – 6648Combined sources
      Helixi72 – 8615Combined sources
      Turni87 – 893Combined sources
      Helixi104 – 11512Combined sources
      Helixi128 – 16033Combined sources
      Turni163 – 1675Combined sources
      Helixi177 – 19519Combined sources
      Helixi197 – 20610Combined sources
      Beta strandi207 – 2093Combined sources
      Helixi212 – 22312Combined sources
      Beta strandi236 – 2383Combined sources
      Helixi242 – 26827Combined sources
      Helixi271 – 2788Combined sources

      3D structure databases

      Select the link destinations:
      PDBei
      RCSB PDBi
      PDBji
      Links Updated
      EntryMethodResolution (Å)ChainPositionsPDBsum
      3UKMX-ray3.40A/B/C/D19-288[»]
      ProteinModelPortaliO00180.
      SMRiO00180. Positions 19-281.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Region

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Regioni117 – 1226Selectivity filter 11 Publication1 Publication
      Regioni225 – 2306Selectivity filter 21 Publication
      Regioni293 – 2997Important for intracellular retention in recycling endosomes1 Publication

      Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiCOG1226.
      GeneTreeiENSGT00760000118858.
      HOGENOMiHOG000286014.
      HOVERGENiHBG052237.
      InParanoidiO00180.
      KOiK04912.
      OMAiKQLRKMF.
      OrthoDBiEOG7TTQ85.
      PhylomeDBiO00180.
      TreeFamiTF313947.

      Family and domain databases

      InterProiIPR003280. 2pore_dom_K_chnl.
      IPR013099. 2pore_dom_K_chnl_dom.
      IPR003092. 2pore_dom_K_chnl_TASK.
      IPR005408. 2pore_dom_K_chnl_TWIK.
      IPR001779. 2pore_dom_K_chnl_TWIK1.
      [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.

      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

      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. Translation: CAI21792.1.
      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.

      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. Translation: CAI21792.1.
      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
      EntryMethodResolution (Å)ChainPositionsPDBsum
      3UKMX-ray3.40A/B/C/D19-288[»]
      ProteinModelPortaliO00180.
      SMRiO00180. Positions 19-281.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi109976. 4 interactions.
      DIPiDIP-59532N.
      IntActiO00180. 1 interaction.
      STRINGi9606.ENSP00000355580.

      Chemistry

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

      PTM databases

      PhosphoSiteiO00180.

      Polymorphism and mutation databases

      BioMutaiKCNK1.

      Proteomic databases

      MaxQBiO00180.
      PaxDbiO00180.
      PRIDEiO00180.

      Protocols and materials databases

      DNASUi3775.
      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

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

      Organism-specific databases

      CTDi3775.
      GeneCardsiGC01P233750.
      HGNCiHGNC:6272. KCNK1.
      HPAiCAB022588.
      HPA016049.
      MIMi601745. gene.
      neXtProtiNX_O00180.
      PharmGKBiPA219.
      GenAtlasiSearch...

      Phylogenomic databases

      eggNOGiCOG1226.
      GeneTreeiENSGT00760000118858.
      HOGENOMiHOG000286014.
      HOVERGENiHBG052237.
      InParanoidiO00180.
      KOiK04912.
      OMAiKQLRKMF.
      OrthoDBiEOG7TTQ85.
      PhylomeDBiO00180.
      TreeFamiTF313947.

      Enzyme and pathway databases

      ReactomeiREACT_75779. Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK).

      Miscellaneous databases

      ChiTaRSiKCNK1. human.
      GeneWikiiKCNK1.
      GenomeRNAii3775.
      NextBioi14807.
      PROiO00180.
      SOURCEiSearch...

      Gene expression databases

      BgeeiO00180.
      CleanExiHS_KCNK1.
      ExpressionAtlasiO00180. baseline and differential.
      GenevisibleiO00180. HS.

      Family and domain databases

      InterProiIPR003280. 2pore_dom_K_chnl.
      IPR013099. 2pore_dom_K_chnl_dom.
      IPR003092. 2pore_dom_K_chnl_TASK.
      IPR005408. 2pore_dom_K_chnl_TWIK.
      IPR001779. 2pore_dom_K_chnl_TWIK1.
      [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...

      Publicationsi

      « Hide 'large scale' publications
      1. "TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure."
        Lesage F., Guillemare E., Fink M., Duprat F., Lazdunski M., Romey G., Barhanin J.
        EMBO J. 15:1004-1011(1996) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-161, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
        Tissue: Kidney.
      2. "Sequence and function of the two P domain potassium channels: implications of an emerging superfamily."
        Goldstein S.A.N., Wang K.-W., Ilan N., Pausch M.H.
        J. Mol. Med. 76:13-20(1998) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [MRNA], REVIEW.
        Tissue: Brain.
      3. "Cloning and localization of a double-pore K channel, KCNK1: exclusive expression in distal nephron segments."
        Orias M., Velazquez H., Tung F., Lee G., Desir G.V.
        Am. J. Physiol. 273:F663-F666(1997) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      4. "The DNA sequence and biological annotation of human chromosome 1."
        Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
        , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
        Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
        The MGC Project Team
        Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
        Tissue: Brain.
      7. "Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge."
        Lesage F., Reyes R., Fink M., Duprat F., Guillemare E., Lazdunski M.
        EMBO J. 15:6400-6407(1996) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, DISULFIDE BOND, GLYCOSYLATION AT ASN-95, MUTAGENESIS OF CYS-69 AND ASN-95, SUBCELLULAR LOCATION, TOPOLOGY.
      8. "Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery."
        Medhurst A.D., Rennie G., Chapman C.G., Meadows H., Duckworth M.D., Kelsell R.E., Gloger I.I., Pangalos M.N.
        Brain Res. Mol. Brain Res. 86:101-114(2001) [PubMed] [Europe PMC] [Abstract]
        Cited for: TISSUE SPECIFICITY.
      9. "Sumoylation silences the plasma membrane leak K+ channel K2P1."
        Rajan S., Plant L.D., Rabin M.L., Butler M.H., Goldstein S.A.
        Cell 121:37-47(2005) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, SUMOYLATION AT LYS-274, MUTAGENESIS OF HIS-122 AND LYS-274, INTERACTION WITH UBE2I.
      10. Cited for: LACK OF SUMOYLATION AT LYS-274, MUTAGENESIS OF LYS-274, FUNCTION, SUBCELLULAR LOCATION.
      11. "Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart."
        Gaborit N., Le Bouter S., Szuts V., Varro A., Escande D., Nattel S., Demolombe S.
        J. Physiol. (Lond.) 582:675-693(2007) [PubMed] [Europe PMC] [Abstract]
        Cited for: TISSUE SPECIFICITY.
      12. "Potassium channel silencing by constitutive endocytosis and intracellular sequestration."
        Feliciangeli S., Tardy M.P., Sandoz G., Chatelain F.C., Warth R., Barhanin J., Bendahhou S., Lesage F.
        J. Biol. Chem. 285:4798-4805(2010) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-274; 293-ILE-ILE-294 AND 299-LEU--HIS-336.
      13. Cited for: SUMOYLATION AT LYS-274, MUTAGENESIS OF HIS-122 AND LYS-274, FUNCTION, SUBCELLULAR LOCATION.
      14. "TWIK-1 two-pore domain potassium channels change ion selectivity and conduct inward leak sodium currents in hypokalemia."
        Ma L., Zhang X., Chen H.
        Sci. Signal. 4:RA37-RA37(2011) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-118 AND LYS-274, TISSUE SPECIFICITY, ENZYME REGULATION.
      15. "A role for two-pore K? channels in modulating Na? absorption and Cl? secretion in normal human bronchial epithelial cells."
        Zhao K.Q., Xiong G., Wilber M., Cohen N.A., Kreindler J.L.
        Am. J. Physiol. 302:L4-L12(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
      16. Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF 108-LEU-PHE-109; THR-118; HIS-122; LEU-146; LEU-228; THR-250 AND LYS-274.
      17. "SUMOylation silences heterodimeric TASK potassium channels containing K2P1 subunits in cerebellar granule neurons."
        Plant L.D., Zuniga L., Araki D., Marks J.D., Goldstein S.A.
        Sci. Signal. 5:RA84-RA84(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, FUNCTION, SUMOYLATION, INTERACTION WITH KCNK3 AND KCNK9, MUTAGENESIS OF TYR-231.
      18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      19. "The family of K2P channels: salient structural and functional properties."
        Feliciangeli S., Chatelain F.C., Bichet D., Lesage F.
        J. Physiol. (Lond.) 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
        Cited for: REVIEW.
      20. "A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P potassium channel."
        Aryal P., Abd-Wahab F., Bucci G., Sansom M.S., Tucker S.J.
        Nat. Commun. 5:4377-4377(2014) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-146 AND LEU-261, SITE.
      21. "Silent but not dumb: how cellular trafficking and pore gating modulate expression of TWIK1 and THIK2."
        Bichet D., Blin S., Feliciangeli S., Chatelain F.C., Bobak N., Lesage F.
        Pflugers Arch. 467:1121-1131(2015) [PubMed] [Europe PMC] [Abstract]
        Cited for: REVIEW.
      22. "Crystal structure of the human two-pore domain potassium channel K2P1."
        Miller A.N., Long S.B.
        Science 335:432-436(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 23-288 IN COMPLEX WITH POTASSIUM IONS, FUNCTION, SUBUNIT, DISULFIDE BOND, TOPOLOGY, SUBCELLULAR LOCATION.

      Entry informationi

      Entry nameiKCNK1_HUMAN
      AccessioniPrimary (citable) accession number: O00180
      Secondary accession number(s): Q13307, Q5T5E8
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: February 21, 2001
      Last sequence update: July 1, 1997
      Last modified: July 22, 2015
      This is version 141 of the entry and version 1 of the sequence. [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

      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 5mM, 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

      Keywords - Technical termi

      3D-structure, Complete proteome, Reference proteome

      Documents

      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

      External Data

      Dasty 3

      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 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.