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Q6VV64

- KCNKI_MOUSE

UniProt

Q6VV64 - KCNKI_MOUSE

Protein

Potassium channel subfamily K member 18

Gene

Kcnk18

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 92 (01 Oct 2014)
      Sequence version 1 (05 Jul 2004)
      Previous versions | rss
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    Functioni

    Outward rectifying potassium channel. Produces rapidly activating outward rectifier K+ currents. May function as background potassium channel that sets the resting membrane potential. Channel activity is directly activated by calcium signal. Activated by the G(q)-protein coupled receptor pathway. The calcium signal robustly activates the channel via calcineurin, whereas the anchoring of 14-3-3/YWHAH interferes with the return of the current to the resting state after activation. Inhibited also by arachidonic acid and other naturally occurring unsaturated free fatty acids. Channel activity is also enhanced by volatile anesthetics, such as isoflurane. Appears to be the primary target of hydroxy-alpha-sanshool, an ingredient of Schezuan pepper. May be involved in the somatosensory function with special respect to pain sensation.3 Publications

    GO - Molecular functioni

    1. calcium-activated potassium channel activity Source: UniProtKB
    2. outward rectifier potassium channel activity Source: Ensembl
    3. protein binding Source: UniProtKB

    GO - Biological processi

    1. cellular response to pH Source: Ensembl
    2. potassium ion export Source: Ensembl
    3. potassium ion transport Source: UniProtKB

    Keywords - Molecular functioni

    Ion channel, Potassium channel

    Keywords - Biological processi

    Ion transport, Potassium transport, Transport

    Keywords - Ligandi

    Potassium

    Enzyme and pathway databases

    ReactomeiREACT_199068. TWIK-related spinal cord K+ channel (TRESK).

    Protein family/group databases

    TCDBi1.A.1.18.1. the voltage-gated ion channel (vic) superfamily.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Potassium channel subfamily K member 18
    Alternative name(s):
    Two-pore-domain potassium channel TRESK
    Gene namesi
    Name:Kcnk18
    Synonyms:Tresk-2, Tresk2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 19

    Organism-specific databases

    MGIiMGI:2685627. Kcnk18.

    Subcellular locationi

    Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi83 – 831N → Q: Strongly reduced current amplitude and localization to cell membrane. 1 Publication
    Mutagenesisi132 – 1321H → N: Insensitive to extracellular protons. 1 Publication
    Mutagenesisi212 – 2121I → A: Loss of interaction with calcineurin and activation by elevated intracellular calcium; when associated with A-214.
    Mutagenesisi214 – 2141I → A: Strongly reduced activation by elevated intracellular calcium. Loss of interaction with calcineurin and activation by elevated intracellular calcium; when associated with A-212.
    Mutagenesisi264 – 2641S → A: Loss of interaction with YWHAH. 1 Publication
    Mutagenesisi276 – 2761S → A: Enhances basal channel activity and abolishes stimulation by calcineurin. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 394394Potassium channel subfamily K member 18PRO_0000312501Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi83 – 831N-linked (GlcNAc...)1 Publication
    Modified residuei264 – 2641Phosphoserine1 Publication
    Modified residuei276 – 2761Phosphoserine1 Publication

    Post-translational modificationi

    Phosphorylation of Ser-264 is required for the binding of 14-3-3eta/YWHAH. Calcineurin-mediated dephosphorylation of Ser-276 enhances channel activity.2 Publications
    N-glycosylated.1 Publication

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PRIDEiQ6VV64.

    PTM databases

    PhosphoSiteiQ6VV64.

    Expressioni

    Tissue specificityi

    Detected in brain cortex, cerebellum, dorsal root ganglion, spinal cord and testis. High expression in trigeminal ganglion, also expressed in autonomic nervous system ganglia such as the stellate ganglion and paravertebral sympathetic ganglia. Expressed in all adult spinal cord and brain regions, with slightly higher expression in thalamus, hypothalamus, hippocampus and posterior corte (at protein level). In non-neuronal tissues, substantial expression found in lung and heart and weal expression in liver, testis, kidney, small intestine and spleen.4 Publications

    Developmental stagei

    Expression appears in trigeminal ganglion and dorsal root ganglia from E15.5 and increased through E18 to reach a peak in newborn mouse postnatal day 1.1 Publication

    Gene expression databases

    BgeeiQ6VV64.
    CleanExiMM_KCNK18.
    GenevestigatoriQ6VV64.

    Interactioni

    Subunit structurei

    Interacts with calcineurin. Interacts with YWHAH, in a phosphorylation-dependent manner.2 Publications

    Protein-protein interaction databases

    IntActiQ6VV64. 1 interaction.
    MINTiMINT-7997383.
    STRINGi10090.ENSMUSP00000065713.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6VV64.
    SMRiQ6VV64. Positions 44-181.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3131CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini163 – 292130CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini368 – 39427CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei114 – 14027Pore-forming; Name=Pore-forming 1Sequence AnalysisAdd
    BLAST
    Intramembranei326 – 34015Pore-forming; Name=Pore-forming 2Sequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei32 – 5221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei142 – 16221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei293 – 31321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei347 – 36721HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni210 – 2156Interaction with calcineurin
    Regioni261 – 2666Interaction with YWHAH

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG311880.
    GeneTreeiENSGT00700000104522.
    HOGENOMiHOG000074045.
    HOVERGENiHBG104673.
    InParanoidiQ6VV64.
    OMAiAFKLVQN.
    OrthoDBiEOG7MPRDX.
    PhylomeDBiQ6VV64.
    TreeFamiTF316115.

    Family and domain databases

    InterProiIPR003280. 2pore_dom_K_chnl.
    IPR013099. 2pore_dom_K_chnl_dom.
    IPR003092. 2pore_dom_K_chnl_TASK.
    [Graphical view]
    PfamiPF07885. Ion_trans_2. 2 hits.
    [Graphical view]
    PRINTSiPR01333. 2POREKCHANEL.
    PR01095. TASKCHANNEL.

    Sequencei

    Sequence statusi: Complete.

    Q6VV64-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEAEEPPEAR RCCPEALGKA RGCCPEALGK LLPGLCFLCC LVTYALVGAA    50
    LFSAVEGRPD PEAEENPELK KFLDDLCNIL KCNLTVVEGS RKNLCEHLQH 100
    LKPQWLKAPQ DWSFLSALFF CCTVFSTVGY GHMYPVTRLG KFLCMLYALF 150
    GIPLMFLVLT DIGDILATIL SRAYSRFQAL LCLPHDIFKW RSLPLCRKQP 200
    DSKPVEEAIP QIVIDAGVDE LLNPQPSKDP PSPSCNVELF ERLVAREKKN 250
    KLQPPTRPVE RSNSCPELVL GRLSCSILSN LDEVGQQVER LDIPLPVIAL 300
    VVFAYISCAA AILPFWETEL GFEDAFYFCF VTLTTIGFGD IVLVHPHFFL 350
    FFSIYIIVGM EILFIAFKLM QNRLLHTYKT LMLFVCQREV SLPW 394
    Length:394
    Mass (Da):44,403
    Last modified:July 5, 2004 - v1
    Checksum:i82D03F7D7F0D5591
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti228 – 2281K → R in AAI15706. (PubMed:15489334)Curated
    Sequence conflicti228 – 2281K → R in AAI04133. (PubMed:15489334)Curated
    Sequence conflicti251 – 2511K → E in AAI15706. (PubMed:15489334)Curated
    Sequence conflicti251 – 2511K → E in AAI04133. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY325301 mRNA. Translation: AAQ91836.1.
    AY542902 mRNA. Translation: AAS48426.1.
    AK139600 mRNA. Translation: BAE24080.1.
    AK162136 mRNA. Translation: BAE36746.1.
    BC104132 mRNA. Translation: AAI04133.1.
    BC104133 mRNA. Translation: AAI04134.1.
    BC115705 mRNA. Translation: AAI15706.1.
    BC115887 mRNA. Translation: AAI15888.1.
    BC127136 mRNA. Translation: AAI27137.1.
    BC127137 mRNA. Translation: AAI27138.1.
    CCDSiCCDS29934.1.
    RefSeqiNP_997144.1. NM_207261.3.
    UniGeneiMm.329947.

    Genome annotation databases

    EnsembliENSMUST00000065204; ENSMUSP00000065713; ENSMUSG00000040901.
    GeneIDi332396.
    KEGGimmu:332396.
    UCSCiuc008ibh.1. mouse.

    Cross-referencesi

    Web resourcesi

    Protein Spotlight

    Throb - Issue 124 of December 2010

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY325301 mRNA. Translation: AAQ91836.1 .
    AY542902 mRNA. Translation: AAS48426.1 .
    AK139600 mRNA. Translation: BAE24080.1 .
    AK162136 mRNA. Translation: BAE36746.1 .
    BC104132 mRNA. Translation: AAI04133.1 .
    BC104133 mRNA. Translation: AAI04134.1 .
    BC115705 mRNA. Translation: AAI15706.1 .
    BC115887 mRNA. Translation: AAI15888.1 .
    BC127136 mRNA. Translation: AAI27137.1 .
    BC127137 mRNA. Translation: AAI27138.1 .
    CCDSi CCDS29934.1.
    RefSeqi NP_997144.1. NM_207261.3.
    UniGenei Mm.329947.

    3D structure databases

    ProteinModelPortali Q6VV64.
    SMRi Q6VV64. Positions 44-181.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q6VV64. 1 interaction.
    MINTi MINT-7997383.
    STRINGi 10090.ENSMUSP00000065713.

    Protein family/group databases

    TCDBi 1.A.1.18.1. the voltage-gated ion channel (vic) superfamily.

    PTM databases

    PhosphoSitei Q6VV64.

    Proteomic databases

    PRIDEi Q6VV64.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000065204 ; ENSMUSP00000065713 ; ENSMUSG00000040901 .
    GeneIDi 332396.
    KEGGi mmu:332396.
    UCSCi uc008ibh.1. mouse.

    Organism-specific databases

    CTDi 338567.
    MGIi MGI:2685627. Kcnk18.

    Phylogenomic databases

    eggNOGi NOG311880.
    GeneTreei ENSGT00700000104522.
    HOGENOMi HOG000074045.
    HOVERGENi HBG104673.
    InParanoidi Q6VV64.
    OMAi AFKLVQN.
    OrthoDBi EOG7MPRDX.
    PhylomeDBi Q6VV64.
    TreeFami TF316115.

    Enzyme and pathway databases

    Reactomei REACT_199068. TWIK-related spinal cord K+ channel (TRESK).

    Miscellaneous databases

    NextBioi 399876.
    PROi Q6VV64.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q6VV64.
    CleanExi MM_KCNK18.
    Genevestigatori Q6VV64.

    Family and domain databases

    InterProi IPR003280. 2pore_dom_K_chnl.
    IPR013099. 2pore_dom_K_chnl_dom.
    IPR003092. 2pore_dom_K_chnl_TASK.
    [Graphical view ]
    Pfami PF07885. Ion_trans_2. 2 hits.
    [Graphical view ]
    PRINTSi PR01333. 2POREKCHANEL.
    PR01095. TASKCHANNEL.
    ProtoNeti Search...

    Publicationsi

    1. "The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin."
      Czirjak G., Toth Z.E., Enyedi P.
      J. Biol. Chem. 279:18550-18558(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, MUTAGENESIS OF SER-276, PHOSPHORYLATION AT SER-276, TISSUE SPECIFICITY.
      Strain: NMRI.
      Tissue: Cerebellum.
    2. "Species-specific differences in response to anesthetics and other modulators by the K2P channel TRESK."
      Keshavaprasad B., Liu C., Au J.D., Kindler C.H., Cotten J.F., Yost C.S.
      Anesth. Analg. 101:1042-1049(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION.
      Strain: BALB/c.
      Tissue: Spinal cord.
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Egg.
    4. "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].
    5. "Targeting of calcineurin to an NFAT-like docking site is required for the calcium-dependent activation of the background K+ channel, TRESK."
      Czirjak G., Enyedi P.
      J. Biol. Chem. 281:14677-14682(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CALCINEURIN.
    6. "TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones."
      Dobler T., Springauf A., Tovornik S., Weber M., Schmitt A., Sedlmeier R., Wischmeyer E., Doring F.
      J. Physiol. (Lond.) 585:867-879(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, MUTAGENESIS OF HIS-132.
    7. "Phosphorylation-dependent binding of 14-3-3 proteins controls TRESK regulation."
      Czirjak G., Vuity D., Enyedi P.
      J. Biol. Chem. 283:15672-15680(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH YWHAH, MUTAGENESIS OF SER-264, PHOSPHORYLATION AT SER-264.
    8. "Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels."
      Bautista D.M., Sigal Y.M., Milstein A.D., Garrison J.L., Zorn J.A., Tsuruda P.R., Nicoll R.A., Julius D.
      Nat. Neurosci. 11:772-779(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    9. "N-linked glycosylation determines cell surface expression of two-pore-domain K+ channel TRESK."
      Egenberger B., Polleichtner G., Wischmeyer E., Doring F.
      Biochem. Biophys. Res. Commun. 391:1262-1267(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-83, MUTAGENESIS OF ASN-83.
    10. Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.

    Entry informationi

    Entry nameiKCNKI_MOUSE
    AccessioniPrimary (citable) accession number: Q6VV64
    Secondary accession number(s): Q1LZJ5
    , Q1LZM8, Q3MI50, Q3MI51
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 4, 2007
    Last sequence update: July 5, 2004
    Last modified: October 1, 2014
    This is version 92 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Regulated by extracellular protons whereas human ortholog is not. His-132 is responsible for proton-dependent specific activity.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Protein Spotlight
      Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3