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Q7Z418

- KCNKI_HUMAN

UniProt

Q7Z418 - KCNKI_HUMAN

Protein

Potassium channel subfamily K member 18

Gene

KCNK18

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 96 (01 Oct 2014)
      Sequence version 1 (01 Oct 2003)
      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 By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei96 – 961Not glycosylated

    GO - Molecular functioni

    1. calcium-activated potassium channel activity Source: Ensembl
    2. outward rectifier potassium channel activity Source: BHF-UCL
    3. potassium channel activity Source: Reactome

    GO - Biological processi

    1. cellular response to pH Source: BHF-UCL
    2. potassium ion export Source: BHF-UCL
    3. potassium ion transport Source: UniProtKB
    4. synaptic transmission Source: Reactome

    Keywords - Molecular functioni

    Ion channel, Potassium channel

    Keywords - Biological processi

    Ion transport, Potassium transport, Transport

    Keywords - Ligandi

    Potassium

    Enzyme and pathway databases

    ReactomeiREACT_75801. TWIK-related spinal cord K+ channel (TRESK).

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Potassium channel subfamily K member 18
    Alternative name(s):
    TWIK-related individual potassium channel
    TWIK-related spinal cord potassium channel
    Gene namesi
    Name:KCNK18
    Synonyms:TRESK, TRIK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:19439. KCNK18.

    Subcellular locationi

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

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Migraine with or without aura 13 (MGR13) [MIM:613656]: A form of migraine transmitted in an autosomal dominant pattern. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. The two major subtypes are common migraine (migraine without aura) and classic migraine (migraine with aura). Classic migraine is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry. Susceptibility to migraine has been shown to be conferred by a frameshift mutation that segregates with the disorder in a large multigenerational family. Migraine was associated with sensitivity to lights, sounds, and smells, as well as nausea and occasional vomiting. Triggers included fatigue, alcohol and bright lights. Mutations in KCNK18 are a rare cause of migraine.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi70 – 701N → Q: Strongly reduced current amplitude and localization to cell membrane. Strongly reduced current amplitude and localization to cell membrane; when associated with Q-96. 1 Publication
    Mutagenesisi96 – 961N → Q: Strongly reduced current amplitude and localization to cell membrane. Strongly reduced current amplitude and localization to cell membrane; when associated with Q-70. 1 Publication
    Mutagenesisi121 – 1211Y → H: Restores sensitivity to extracellular protons. 1 Publication

    Organism-specific databases

    MIMi613656. phenotype.
    PharmGKBiPA134985465.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 384384Potassium channel subfamily K member 18PRO_0000312500Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi70 – 701N-linked (GlcNAc...)1 Publication
    Modified residuei252 – 2521PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylation of Ser-252 is required for the binding of 14-3-3eta/YWHAH. Calcineurin-mediated dephosphorylation of Ser-264 enhances channel activity By similarity.By similarity
    N-glycosylated.1 Publication

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiQ7Z418.
    PRIDEiQ7Z418.

    PTM databases

    PhosphoSiteiQ7Z418.

    Expressioni

    Tissue specificityi

    Expressed specifically in dorsal root ganglion and trigeminal ganglion neurons. Detected at low levels in spinal cord.3 Publications

    Gene expression databases

    CleanExiHS_KCNK18.
    GenevestigatoriQ7Z418.

    Organism-specific databases

    HPAiHPA044739.

    Interactioni

    Subunit structurei

    Interacts with calcineurin. Interacts with YWHAH, in a phosphorylation-dependent manner.By similarity

    Protein-protein interaction databases

    BioGridi130759. 2 interactions.
    STRINGi9606.ENSP00000334650.

    Structurei

    3D structure databases

    ProteinModelPortaliQ7Z418.
    SMRiQ7Z418. Positions 33-168.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2323CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini149 – 280132CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini356 – 38429CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei103 – 12927Pore-forming; Name=Pore-forming 1Sequence AnalysisAdd
    BLAST
    Intramembranei314 – 32815Pore-forming; Name=Pore-forming 2Sequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei24 – 4421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei130 – 14819HelicalSequence AnalysisAdd
    BLAST
    Transmembranei281 – 30121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei335 – 35521HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni200 – 2056Interaction with calcineurinBy similarity
    Regioni249 – 2546Interaction with YWHAHBy similarity

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG311880.
    HOGENOMiHOG000074045.
    HOVERGENiHBG104673.
    InParanoidiQ7Z418.
    OMAiAFKLVQN.
    OrthoDBiEOG7MPRDX.
    PhylomeDBiQ7Z418.
    TreeFamiTF316115.

    Family and domain databases

    InterProiIPR003280. 2pore_dom_K_chnl.
    IPR013099. 2pore_dom_K_chnl_dom.
    [Graphical view]
    PfamiPF07885. Ion_trans_2. 2 hits.
    [Graphical view]
    PRINTSiPR01333. 2POREKCHANEL.

    Sequencei

    Sequence statusi: Complete.

    Q7Z418-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEVSGHPQAR RCCPEALGKL FPGLCFLCFL VTYALVGAVV FSAIEDGQVL    50
    VAADDGEFEK FLEELCRILN CSETVVEDRK QDLQGHLQKV KPQWFNRTTH 100
    WSFLSSLFFC CTVFSTVGYG YIYPVTRLGK YLCMLYALFG IPLMFLVLTD 150
    TGDILATILS TSYNRFRKFP FFTRPLLSKW CPKSLFKKKP DPKPADEAVP 200
    QIIISAEELP GPKLGTCPSR PSCSMELFER SHALEKQNTL QLPPQAMERS 250
    NSCPELVLGR LSYSIISNLD EVGQQVERLD IPLPIIALIV FAYISCAAAI 300
    LPFWETQLDF ENAFYFCFVT LTTIGFGDTV LEHPNFFLFF SIYIIVGMEI 350
    VFIAFKLVQN RLIDIYKNVM LFFAKGKFYH LVKK 384
    Length:384
    Mass (Da):43,671
    Last modified:October 1, 2003 - v1
    Checksum:i5D0B544F815ACB1C
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti34 – 341A → V.1 Publication
    VAR_064027
    Natural varianti58 – 581F → Y.
    Corresponds to variant rs3909165 [ dbSNP | Ensembl ].
    VAR_037521
    Natural varianti198 – 1981A → G.
    Corresponds to variant rs363359 [ dbSNP | Ensembl ].
    VAR_037522
    Natural varianti231 – 2311S → P.
    Corresponds to variant rs363315 [ dbSNP | Ensembl ].
    VAR_037523
    Natural varianti233 – 2331A → V.1 Publication
    Corresponds to variant rs363360 [ dbSNP | Ensembl ].
    VAR_037524
    Natural varianti255 – 2551E → K.
    Corresponds to variant rs3026042 [ dbSNP | Ensembl ].
    VAR_037525
    Natural varianti346 – 3461V → I.
    Corresponds to variant rs12247136 [ dbSNP | Ensembl ].
    VAR_037526

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB087138 mRNA. Translation: BAC78527.1.
    AL731557 Genomic DNA. Translation: CAI14827.2.
    CCDSiCCDS7598.1.
    RefSeqiNP_862823.1. NM_181840.1.
    UniGeneiHs.449650.

    Genome annotation databases

    EnsembliENST00000334549; ENSP00000334650; ENSG00000186795.
    GeneIDi338567.
    KEGGihsa:338567.
    UCSCiuc010qsr.2. human.

    Polymorphism databases

    DMDMi74750072.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Protein Spotlight

    Throb - Issue 124 of December 2010

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB087138 mRNA. Translation: BAC78527.1 .
    AL731557 Genomic DNA. Translation: CAI14827.2 .
    CCDSi CCDS7598.1.
    RefSeqi NP_862823.1. NM_181840.1.
    UniGenei Hs.449650.

    3D structure databases

    ProteinModelPortali Q7Z418.
    SMRi Q7Z418. Positions 33-168.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 130759. 2 interactions.
    STRINGi 9606.ENSP00000334650.

    Chemistry

    ChEMBLi CHEMBL2331042.
    GuidetoPHARMACOLOGYi 527.

    PTM databases

    PhosphoSitei Q7Z418.

    Polymorphism databases

    DMDMi 74750072.

    Proteomic databases

    PaxDbi Q7Z418.
    PRIDEi Q7Z418.

    Protocols and materials databases

    DNASUi 338567.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000334549 ; ENSP00000334650 ; ENSG00000186795 .
    GeneIDi 338567.
    KEGGi hsa:338567.
    UCSCi uc010qsr.2. human.

    Organism-specific databases

    CTDi 338567.
    GeneCardsi GC10P118947.
    HGNCi HGNC:19439. KCNK18.
    HPAi HPA044739.
    MIMi 613655. gene.
    613656. phenotype.
    neXtProti NX_Q7Z418.
    PharmGKBi PA134985465.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG311880.
    HOGENOMi HOG000074045.
    HOVERGENi HBG104673.
    InParanoidi Q7Z418.
    OMAi AFKLVQN.
    OrthoDBi EOG7MPRDX.
    PhylomeDBi Q7Z418.
    TreeFami TF316115.

    Enzyme and pathway databases

    Reactomei REACT_75801. TWIK-related spinal cord K+ channel (TRESK).

    Miscellaneous databases

    GeneWikii KCNK18.
    GenomeRNAii 338567.
    NextBioi 97036.
    PROi Q7Z418.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_KCNK18.
    Genevestigatori Q7Z418.

    Family and domain databases

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

    Publicationsi

    1. "A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord."
      Sano Y., Inamura K., Miyake A., Mochizuki S., Kitada C., Yokoi H., Nozawa K., Okada H., Matsushime H., Furuichi K.
      J. Biol. Chem. 278:27406-27412(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
      Tissue: Spinal cord.
    2. "The DNA sequence and comparative analysis of human chromosome 10."
      Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
      , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
      Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "Potent activation of the human tandem pore domain K channel TRESK with clinical concentrations of volatile anesthetics."
      Liu C., Au J.D., Zou H.L., Cotten J.F., Yost C.S.
      Anesth. Analg. 99:1715-1722(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    4. "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: MUTAGENESIS OF TYR-121.
    5. "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-70, MUTAGENESIS OF ASN-70 AND ASN-96.
    6. Cited for: TISSUE SPECIFICITY, INVOLVEMENT IN MGR13, VARIANTS VAL-34 AND VAL-233.

    Entry informationi

    Entry nameiKCNKI_HUMAN
    AccessioniPrimary (citable) accession number: Q7Z418
    Secondary accession number(s): Q5SQQ8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 4, 2007
    Last sequence update: October 1, 2003
    Last modified: October 1, 2014
    This is version 96 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

    In contrast to its mouse ortholog, it is not regulated by extracellular protons.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Protein Spotlight
      Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3