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Q7Z418

- KCNKI_HUMAN

UniProt

Q7Z418 - KCNKI_HUMAN

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Protein

Potassium channel subfamily K member 18

Gene
KCNK18, TRESK, TRIK
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.2 Publications

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
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_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; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2323Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei24 – 4421Helical; Reviewed predictionAdd
BLAST
Intramembranei103 – 12927Pore-forming; Name=Pore-forming 1; Reviewed predictionAdd
BLAST
Transmembranei130 – 14819Helical; Reviewed predictionAdd
BLAST
Topological domaini149 – 280132Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei281 – 30121Helical; Reviewed predictionAdd
BLAST
Intramembranei314 – 32815Pore-forming; Name=Pore-forming 2; Reviewed predictionAdd
BLAST
Transmembranei335 – 35521Helical; Reviewed predictionAdd
BLAST
Topological domaini356 – 38429Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

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

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.
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.1 Publication

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 – 2521Phosphoserine By 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.
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 By similarity. 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.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni200 – 2056Interaction with calcineurin By similarity
Regioni249 – 2546Interaction with YWHAH By 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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 95 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

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