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Q7Z418 (KCNKI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Potassium channel subfamily K member 18
Alternative name(s):
TWIK-related individual potassium channel
TWIK-related spinal cord potassium channel
Gene names
Name:KCNK18
Synonyms:TRESK, TRIK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length384 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.3

Subunit structure

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

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.5.

Tissue specificity

Expressed specifically in dorsal root ganglion and trigeminal ganglion neurons. Detected at low levels in spinal cord. Ref.1 Ref.3 Ref.6

Post-translational modification

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. Ref.5

Involvement in disease

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. Ref.6

Miscellaneous

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

Sequence similarities

Belongs to the two pore domain potassium channel (TC 1.A.1.8) family. [View classification]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 384384Potassium channel subfamily K member 18
PRO_0000312500

Regions

Topological domain1 – 2323Cytoplasmic Potential
Transmembrane24 – 4421Helical; Potential
Intramembrane103 – 12927Pore-forming; Name=Pore-forming 1; Potential
Transmembrane130 – 14819Helical; Potential
Topological domain149 – 280132Cytoplasmic Potential
Transmembrane281 – 30121Helical; Potential
Intramembrane314 – 32815Pore-forming; Name=Pore-forming 2; Potential
Transmembrane335 – 35521Helical; Potential
Topological domain356 – 38429Cytoplasmic Potential
Region200 – 2056Interaction with calcineurin By similarity
Region249 – 2546Interaction with YWHAH By similarity

Sites

Site961Not glycosylated

Amino acid modifications

Modified residue2521Phosphoserine By similarity
Glycosylation701N-linked (GlcNAc...) Ref.5

Natural variations

Natural variant341A → V. Ref.6
VAR_064027
Natural variant581F → Y.
Corresponds to variant rs3909165 [ dbSNP | Ensembl ].
VAR_037521
Natural variant1981A → G.
Corresponds to variant rs363359 [ dbSNP | Ensembl ].
VAR_037522
Natural variant2311S → P.
Corresponds to variant rs363315 [ dbSNP | Ensembl ].
VAR_037523
Natural variant2331A → V. Ref.6
Corresponds to variant rs363360 [ dbSNP | Ensembl ].
VAR_037524
Natural variant2551E → K.
Corresponds to variant rs3026042 [ dbSNP | Ensembl ].
VAR_037525
Natural variant3461V → I.
Corresponds to variant rs12247136 [ dbSNP | Ensembl ].
VAR_037526

Experimental info

Mutagenesis701N → Q: Strongly reduced current amplitude and localization to cell membrane. Strongly reduced current amplitude and localization to cell membrane; when associated with Q-96. Ref.5
Mutagenesis961N → Q: Strongly reduced current amplitude and localization to cell membrane. Strongly reduced current amplitude and localization to cell membrane; when associated with Q-70. Ref.5
Mutagenesis1211Y → H: Restores sensitivity to extracellular protons. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q7Z418 [UniParc].

Last modified October 1, 2003. Version 1.
Checksum: 5D0B544F815ACB1C

FASTA38443,671
        10         20         30         40         50         60 
MEVSGHPQAR RCCPEALGKL FPGLCFLCFL VTYALVGAVV FSAIEDGQVL VAADDGEFEK 

        70         80         90        100        110        120 
FLEELCRILN CSETVVEDRK QDLQGHLQKV KPQWFNRTTH WSFLSSLFFC CTVFSTVGYG 

       130        140        150        160        170        180 
YIYPVTRLGK YLCMLYALFG IPLMFLVLTD TGDILATILS TSYNRFRKFP FFTRPLLSKW 

       190        200        210        220        230        240 
CPKSLFKKKP DPKPADEAVP QIIISAEELP GPKLGTCPSR PSCSMELFER SHALEKQNTL 

       250        260        270        280        290        300 
QLPPQAMERS NSCPELVLGR LSYSIISNLD EVGQQVERLD IPLPIIALIV FAYISCAAAI 

       310        320        330        340        350        360 
LPFWETQLDF ENAFYFCFVT LTTIGFGDTV LEHPNFFLFF SIYIIVGMEI VFIAFKLVQN 

       370        380 
RLIDIYKNVM LFFAKGKFYH LVKK 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura."
Lafreniere R.G., Cader M.Z., Poulin J.F., Andres-Enguix I., Simoneau M., Gupta N., Boisvert K., Lafreniere F., McLaughlan S., Dube M.P., Marcinkiewicz M.M., Ramagopalan S., Ansorge O., Brais B., Sequeiros J., Pereira-Monteiro J.M., Griffiths L.R., Tucker S.J., Ebers G., Rouleau G.A.
Nat. Med. 16:1157-1160(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INVOLVEMENT IN MGR13, VARIANTS VAL-34 AND VAL-233.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Throb - Issue 124 of December 2010

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB087138 mRNA. Translation: BAC78527.1.
AL731557 Genomic DNA. Translation: CAI14827.2.
RefSeqNP_862823.1. NM_181840.1.
UniGeneHs.449650.

3D structure databases

ProteinModelPortalQ7Z418.
SMRQ7Z418. Positions 33-168, 307-365.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid130759. 2 interactions.
STRING9606.ENSP00000334650.

Chemistry

ChEMBLCHEMBL2331042.
GuidetoPHARMACOLOGY527.

PTM databases

PhosphoSiteQ7Z418.

Polymorphism databases

DMDM74750072.

Proteomic databases

PaxDbQ7Z418.
PRIDEQ7Z418.

Protocols and materials databases

DNASU338567.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000334549; ENSP00000334650; ENSG00000186795.
GeneID338567.
KEGGhsa:338567.
UCSCuc010qsr.2. human.

Organism-specific databases

CTD338567.
GeneCardsGC10P118947.
HGNCHGNC:19439. KCNK18.
HPAHPA044739.
MIM613655. gene.
613656. phenotype.
neXtProtNX_Q7Z418.
PharmGKBPA134985465.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG311880.
HOGENOMHOG000074045.
HOVERGENHBG104673.
InParanoidQ7Z418.
OMAAFKLVQN.
OrthoDBEOG7MPRDX.
PhylomeDBQ7Z418.
TreeFamTF316115.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

CleanExHS_KCNK18.
GenevestigatorQ7Z418.

Family and domain databases

InterProIPR003280. 2pore_dom_K_chnl.
IPR013099. 2pore_dom_K_chnl_dom.
[Graphical view]
PfamPF07885. Ion_trans_2. 2 hits.
[Graphical view]
PRINTSPR01333. 2POREKCHANEL.
ProtoNetSearch...

Other

GeneWikiKCNK18.
GenomeRNAi338567.
NextBio97036.
PROQ7Z418.
SOURCESearch...

Entry information

Entry nameKCNKI_HUMAN
AccessionPrimary (citable) accession number: Q7Z418
Secondary accession number(s): Q5SQQ8
Entry history
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: October 1, 2003
Last modified: April 16, 2014
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM