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Protein

Potassium channel subfamily K member 2

Gene

Kcnk2

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. Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward rectifying potassium channel in a phosphorylation-dependent manner. In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of functional channels containing homodimeric KCNK2 (PubMed:24496152). 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).4 Publications

Enzyme regulationi

Inhibited by barium (PubMed:9003761). Activated by volatile general anesthetics such as chloroform, diethyl ether, halothane and isoflurane (PubMed:10321245).2 Publications

Kineticsi

Channel activation is extremely rapid (PubMed:9003761). Single channel conductance is about 14 pS (PubMed:9003761).1 Publication

      GO - Molecular functioni

      GO - Biological processi

      Complete GO annotation...

      Keywords - Molecular functioni

      Ion channel, Potassium channel

      Keywords - Biological processi

      Ion transport, Potassium transport, Transport

      Keywords - Ligandi

      Potassium

      Enzyme and pathway databases

      ReactomeiR-MMU-1299503. TWIK related potassium channel (TREK).

      Protein family/group databases

      TCDBi1.A.1.9.1. the voltage-gated ion channel (vic) superfamily.

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Potassium channel subfamily K member 2
      Alternative name(s):
      Outward rectifying potassium channel protein TREK-1
      TREK-1 K(+) channel subunit2 Publications
      Two pore potassium channel TPKC1
      Gene namesi
      Name:Kcnk2
      OrganismiMus musculus (Mouse)
      Taxonomic identifieri10090 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
      Proteomesi
      • UP000000589 Componenti: Chromosome 1

      Organism-specific databases

      MGIiMGI:109366. Kcnk2.

      Subcellular locationi

      Isoform 1 :
      Isoform 2 :

      Topology

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Topological domaini1 – 6161CytoplasmicSequence analysisAdd
      BLAST
      Transmembranei62 – 8221HelicalSequence analysisAdd
      BLAST
      Intramembranei144 – 17027Pore-forming; Name=Pore-forming 1Sequence analysisAdd
      BLAST
      Transmembranei172 – 19221HelicalSequence analysisAdd
      BLAST
      Topological domaini193 – 22230CytoplasmicSequence analysisAdd
      BLAST
      Transmembranei223 – 24321HelicalSequence analysisAdd
      BLAST
      Intramembranei253 – 28331Pore-forming; Name=Pore-forming 2Sequence analysisAdd
      BLAST
      Transmembranei288 – 30821HelicalSequence analysisAdd
      BLAST
      Topological domaini309 – 426118CytoplasmicSequence analysisAdd
      BLAST

      GO - Cellular componenti

      Complete GO annotation...

      Keywords - Cellular componenti

      Cell membrane, Membrane

      Pathology & Biotechi

      Mutagenesis

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Mutagenesisi108 – 1081C → S: Abolishes formation of a disulfide-linked heterodimer with KCNK1. 1 Publication

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Chaini1 – 426426Potassium channel subfamily K member 2PRO_0000101743Add
      BLAST

      Amino acid modifications

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Disulfide bondi108 – 108Interchain1 Publication
      Glycosylationi110 – 1101N-linked (GlcNAc...)Sequence analysis
      Glycosylationi134 – 1341N-linked (GlcNAc...)Sequence analysis
      Modified residuei348 – 3481PhosphoserineCombined sources

      Post-translational modificationi

      Phosphorylation at Ser-348 controls the reversible conversion from a leak channel to a voltage-dependent channel.By similarity

      Keywords - PTMi

      Disulfide bond, Glycoprotein, Phosphoprotein

      Proteomic databases

      PaxDbiP97438.
      PRIDEiP97438.

      PTM databases

      PhosphoSiteiP97438.

      Expressioni

      Tissue specificityi

      Detected in hippocampus astrocytes (at protein level) (PubMed:24496152). High expression in brain and lung. Also detected in kidney, heart and skeletal muscle. Not detected in liver. In the brain, highest expression in olfactory bulb, hippocampus and cerebellum.2 Publications

      Gene expression databases

      CleanExiMM_KCNK2.
      ExpressionAtlasiP97438. baseline and differential.
      GenevisibleiP97438. MM.

      Interactioni

      Subunit structurei

      Homodimer; disulfide-linked (PubMed:24496152). Heterodimer with KCNK1; disulfide-linked (PubMed:24496152). Interacts with KCNK2; the interaction enhances KCNK2 surface expression (PubMed:26642364).Curated2 Publications

      Binary interactionsi

      WithEntry#Exp.IntActNotes
      Akap5D3YVF03EBI-7091062,EBI-7091108

      Protein-protein interaction databases

      DIPiDIP-58579N.
      IntActiP97438. 2 interactions.
      STRINGi10090.ENSMUSP00000078416.

      Structurei

      3D structure databases

      ProteinModelPortaliP97438.
      SMRiP97438. Positions 54-317.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Region

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Regioni369 – 42658Required for basal channel activityAdd
      BLAST
      Regioni393 – 42634Essential for chloroform and halothane sensitivityAdd
      BLAST

      Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiKOG1418. Eukaryota.
      COG1226. LUCA.
      GeneTreeiENSGT00760000118858.
      HOGENOMiHOG000013106.
      HOVERGENiHBG052234.
      InParanoidiP97438.
      KOiK04913.
      OMAiAINVMKW.
      PhylomeDBiP97438.

      Family and domain databases

      InterProiIPR003280. 2pore_dom_K_chnl.
      IPR003976. 2pore_dom_K_chnl_TREK.
      IPR013099. K_chnl_dom.
      [Graphical view]
      PfamiPF07885. Ion_trans_2. 2 hits.
      [Graphical view]
      PRINTSiPR01333. 2POREKCHANEL.
      PR01499. TREKCHANNEL.

      Sequences (2)i

      Sequence statusi: Complete.

      This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

      Isoform 1 (identifier: P97438-1) [UniParc]FASTAAdd to basket

      Also known as: TREK-1b

      This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

      « Hide

              10         20         30         40         50
      MLASASRERP GYTAGVAAPD LLDPKSAAQN SKPRLSFSSK PTVLASRVES
      60 70 80 90 100
      DSAINVMKWK TVSTIFLVVV LYLIIGATVF KALEQPQEIS QRTTIVIQKQ
      110 120 130 140 150
      TFIAQHACVN STELDELIQQ IVAAINAGII PLGNSSNQVS HWDLGSSFFF
      160 170 180 190 200
      AGTVITTIGF GNISPRTEGG KIFCIIYALL GIPLFGFLLA GVGDQLGTIF
      210 220 230 240 250
      GKGIAKVEDT FIKWNVSQTK IRIISTIIFI LFGCVLFVAL PAVIFKHIEG
      260 270 280 290 300
      WSALDAIYFV VITLTTIGFG DYVAGGSDIE YLDFYKPVVW FWILVGLAYF
      310 320 330 340 350
      AAVLSMIGDW LRVISKKTKE EVGEFRAHAA EWTANVTAEF KETRRRLSVE
      360 370 380 390 400
      IYDKFQRATS VKRKLSAELA GNHNQELTPC RRTLSVNHLT SEREVLPPLL
      410 420
      KAESIYLNGL TPHCAGEDIA VIENMK
      Length:426
      Mass (Da):46,844
      Last modified:April 16, 2014 - v3
      Checksum:i8C298C01F5BDB61A
      GO
      Isoform 2 (identifier: P97438-2) [UniParc]FASTAAdd to basket

      Also known as: TREK-1a

      The sequence of this isoform differs from the canonical sequence as follows:
           2-16: Missing.

      Show »
      Length:411
      Mass (Da):45,328
      Checksum:iE840B1B17E075435
      GO

      Experimental Info

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Sequence conflicti78 – 781T → A in AAC53005 (Ref. 2) Curated

      Alternative sequence

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Alternative sequencei2 – 1615Missing in isoform 2. 1 PublicationVSP_053951Add
      BLAST

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      U73488 mRNA. Translation: AAC53005.2.
      AY736359 mRNA. Translation: AAV48996.1.
      AC121882 Genomic DNA. No translation available.
      AC124527 Genomic DNA. No translation available.
      CCDSiCCDS48480.1. [P97438-1]
      CCDS48481.1. [P97438-2]
      RefSeqiNP_001153322.1. NM_001159850.1. [P97438-1]
      NP_034737.2. NM_010607.3. [P97438-2]
      UniGeneiMm.33304.
      Mm.387016.

      Genome annotation databases

      EnsembliENSMUST00000110920; ENSMUSP00000106545; ENSMUSG00000037624. [P97438-2]
      ENSMUST00000192723; ENSMUSP00000141849; ENSMUSG00000037624. [P97438-2]
      ENSMUST00000193319; ENSMUSP00000141891; ENSMUSG00000037624. [P97438-1]
      GeneIDi16526.
      KEGGimmu:16526.
      UCSCiuc007eak.2. mouse. [P97438-1]
      uc011wyj.2. mouse. [P97438-2]

      Keywords - Coding sequence diversityi

      Alternative splicing

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      U73488 mRNA. Translation: AAC53005.2.
      AY736359 mRNA. Translation: AAV48996.1.
      AC121882 Genomic DNA. No translation available.
      AC124527 Genomic DNA. No translation available.
      CCDSiCCDS48480.1. [P97438-1]
      CCDS48481.1. [P97438-2]
      RefSeqiNP_001153322.1. NM_001159850.1. [P97438-1]
      NP_034737.2. NM_010607.3. [P97438-2]
      UniGeneiMm.33304.
      Mm.387016.

      3D structure databases

      ProteinModelPortaliP97438.
      SMRiP97438. Positions 54-317.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      DIPiDIP-58579N.
      IntActiP97438. 2 interactions.
      STRINGi10090.ENSMUSP00000078416.

      Protein family/group databases

      TCDBi1.A.1.9.1. the voltage-gated ion channel (vic) superfamily.

      PTM databases

      PhosphoSiteiP97438.

      Proteomic databases

      PaxDbiP97438.
      PRIDEiP97438.

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      EnsembliENSMUST00000110920; ENSMUSP00000106545; ENSMUSG00000037624. [P97438-2]
      ENSMUST00000192723; ENSMUSP00000141849; ENSMUSG00000037624. [P97438-2]
      ENSMUST00000193319; ENSMUSP00000141891; ENSMUSG00000037624. [P97438-1]
      GeneIDi16526.
      KEGGimmu:16526.
      UCSCiuc007eak.2. mouse. [P97438-1]
      uc011wyj.2. mouse. [P97438-2]

      Organism-specific databases

      CTDi3776.
      MGIiMGI:109366. Kcnk2.

      Phylogenomic databases

      eggNOGiKOG1418. Eukaryota.
      COG1226. LUCA.
      GeneTreeiENSGT00760000118858.
      HOGENOMiHOG000013106.
      HOVERGENiHBG052234.
      InParanoidiP97438.
      KOiK04913.
      OMAiAINVMKW.
      PhylomeDBiP97438.

      Enzyme and pathway databases

      ReactomeiR-MMU-1299503. TWIK related potassium channel (TREK).

      Miscellaneous databases

      NextBioi289923.
      PROiP97438.
      SOURCEiSearch...

      Gene expression databases

      CleanExiMM_KCNK2.
      ExpressionAtlasiP97438. baseline and differential.
      GenevisibleiP97438. MM.

      Family and domain databases

      InterProiIPR003280. 2pore_dom_K_chnl.
      IPR003976. 2pore_dom_K_chnl_TREK.
      IPR013099. K_chnl_dom.
      [Graphical view]
      PfamiPF07885. Ion_trans_2. 2 hits.
      [Graphical view]
      PRINTSiPR01333. 2POREKCHANEL.
      PR01499. TREKCHANNEL.
      ProtoNetiSearch...

      Publicationsi

      « Hide 'large scale' publications
      1. "Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel."
        Fink M., Duprat F., Lesage F., Reyes R., Romey G., Heurteaux C., Lazdunski M.
        EMBO J. 15:6854-6862(1996) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
        Tissue: Brain.
      2. Fink M., Duprat F., Lesage F., Reyes R., Romey G., Heurteaux C., Lazdunski M.
        Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases
        Cited for: SEQUENCE REVISION.
      3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION.
        Strain: BALB/cJ.
      4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
        Strain: C57BL/6J.
      5. "Inhalational anesthetics activate two-pore-domain background K+ channels."
        Patel A.J., Honore E., Lesage F., Fink M., Romey G., Lazdunski M.
        Nat. Neurosci. 2:422-426(1999) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
      6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-348, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
        Tissue: Brain.
      7. "A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes."
        Hwang E.M., Kim E., Yarishkin O., Woo D.H., Han K.S., Park N., Bae Y., Woo J., Kim D., Park M., Lee C.J., Park J.Y.
        Nat. Commun. 5:3227-3227(2014) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH KCNK1, TISSUE SPECIFICITY, DISULFIDE BOND, MUTAGENESIS OF CYS-108.
      8. Cited for: INTERACTION WITH BVES.

      Entry informationi

      Entry nameiKCNK2_MOUSE
      AccessioniPrimary (citable) accession number: P97438
      Secondary accession number(s): Q4VQI2
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: February 21, 2001
      Last sequence update: April 16, 2014
      Last modified: March 16, 2016
      This is version 130 of the entry and version 3 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.