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Protein

Potassium channel subfamily K member 18

Gene

KCNK18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • cellular response to pH Source: BHF-UCL
  • potassium ion export Source: BHF-UCL
  • potassium ion transport Source: UniProtKB
  • stabilization of membrane potential Source: GO_Central
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

BioCyciZFISH:G66-33339-MONOMER.
ReactomeiR-HSA-1299344. TWIK-related spinal cord K+ channel (TRESK).
R-HSA-5576886. Phase 4 - resting membrane potential.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:19439. KCNK18.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 23CytoplasmicSequence analysisAdd BLAST23
Transmembranei24 – 44HelicalSequence analysisAdd BLAST21
Intramembranei103 – 129Pore-forming; Name=Pore-forming 1Sequence analysisAdd BLAST27
Transmembranei130 – 148HelicalSequence analysisAdd BLAST19
Topological domaini149 – 280CytoplasmicSequence analysisAdd BLAST132
Transmembranei281 – 301HelicalSequence analysisAdd BLAST21
Intramembranei314 – 328Pore-forming; Name=Pore-forming 2Sequence analysisAdd BLAST15
Transmembranei335 – 355HelicalSequence analysisAdd BLAST21
Topological domaini356 – 384CytoplasmicSequence analysisAdd BLAST29

GO - Cellular componenti

  • integral component of plasma membrane Source: BHF-UCL
  • 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)1 Publication
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.
Disease descriptionA 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.
See also OMIM:613656

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi70N → 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 Publication1
Mutagenesisi96N → 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 Publication1
Mutagenesisi121Y → H: Restores sensitivity to extracellular protons. 1 Publication1

Organism-specific databases

DisGeNETi338567.
MalaCardsiKCNK18.
MIMi613656. phenotype.
OpenTargetsiENSG00000186795.
PharmGKBiPA134985465.

Chemistry databases

ChEMBLiCHEMBL2331042.

Polymorphism and mutation databases

BioMutaiKCNK18.
DMDMi74750072.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003125001 – 384Potassium channel subfamily K member 18Add BLAST384

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi70N-linked (GlcNAc...)1 Publication1
Modified residuei252PhosphoserineBy similarity1

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei96Not glycosylated1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ7Z418.
PeptideAtlasiQ7Z418.
PRIDEiQ7Z418.

PTM databases

iPTMnetiQ7Z418.
PhosphoSitePlusiQ7Z418.

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.

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 interactors.
STRINGi9606.ENSP00000334650.

Structurei

3D structure databases

ProteinModelPortaliQ7Z418.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni200 – 205Interaction with calcineurinBy similarity6
Regioni249 – 254Interaction with YWHAHBy similarity6

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1418. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00700000104522.
HOGENOMiHOG000074045.
HOVERGENiHBG104673.
InParanoidiQ7Z418.
KOiK20007.
OMAiAFKLVQN.
OrthoDBiEOG091G0B4G.
PhylomeDBiQ7Z418.
TreeFamiTF316115.

Family and domain databases

InterProiIPR003280. 2pore_dom_K_chnl.
IPR013099. 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

        10         20         30         40         50
MEVSGHPQAR RCCPEALGKL FPGLCFLCFL VTYALVGAVV FSAIEDGQVL
60 70 80 90 100
VAADDGEFEK FLEELCRILN CSETVVEDRK QDLQGHLQKV KPQWFNRTTH
110 120 130 140 150
WSFLSSLFFC CTVFSTVGYG YIYPVTRLGK YLCMLYALFG IPLMFLVLTD
160 170 180 190 200
TGDILATILS TSYNRFRKFP FFTRPLLSKW CPKSLFKKKP DPKPADEAVP
210 220 230 240 250
QIIISAEELP GPKLGTCPSR PSCSMELFER SHALEKQNTL QLPPQAMERS
260 270 280 290 300
NSCPELVLGR LSYSIISNLD EVGQQVERLD IPLPIIALIV FAYISCAAAI
310 320 330 340 350
LPFWETQLDF ENAFYFCFVT LTTIGFGDTV LEHPNFFLFF SIYIIVGMEI
360 370 380
VFIAFKLVQN RLIDIYKNVM LFFAKGKFYH LVKK
Length:384
Mass (Da):43,671
Last modified:October 1, 2003 - v1
Checksum:i5D0B544F815ACB1C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06402734A → V.1 Publication1
Natural variantiVAR_03752158F → Y.Corresponds to variant rs3909165dbSNPEnsembl.1
Natural variantiVAR_037522198A → G.Corresponds to variant rs363359dbSNPEnsembl.1
Natural variantiVAR_037523231S → P.Corresponds to variant rs363315dbSNPEnsembl.1
Natural variantiVAR_037524233A → V.1 PublicationCorresponds to variant rs363360dbSNPEnsembl.1
Natural variantiVAR_037525255E → K.Corresponds to variant rs3026042dbSNPEnsembl.1
Natural variantiVAR_037526346V → I.Corresponds to variant rs12247136dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Protein Spotlight

Throb - Issue 124 of December 2010

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB087138 mRNA. Translation: BAC78527.1.
AL731557 Genomic DNA. Translation: CAI14827.2.
CCDSiCCDS7598.1.
RefSeqiNP_862823.1. NM_181840.1.
UniGeneiHs.449650.

3D structure databases

ProteinModelPortaliQ7Z418.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi130759. 2 interactors.
STRINGi9606.ENSP00000334650.

Chemistry databases

ChEMBLiCHEMBL2331042.

PTM databases

iPTMnetiQ7Z418.
PhosphoSitePlusiQ7Z418.

Polymorphism and mutation databases

BioMutaiKCNK18.
DMDMi74750072.

Proteomic databases

PaxDbiQ7Z418.
PeptideAtlasiQ7Z418.
PRIDEiQ7Z418.

Protocols and materials databases

DNASUi338567.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi338567.
DisGeNETi338567.
GeneCardsiKCNK18.
HGNCiHGNC:19439. KCNK18.
HPAiHPA044739.
MalaCardsiKCNK18.
MIMi613655. gene.
613656. phenotype.
neXtProtiNX_Q7Z418.
OpenTargetsiENSG00000186795.
PharmGKBiPA134985465.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1418. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00700000104522.
HOGENOMiHOG000074045.
HOVERGENiHBG104673.
InParanoidiQ7Z418.
KOiK20007.
OMAiAFKLVQN.
OrthoDBiEOG091G0B4G.
PhylomeDBiQ7Z418.
TreeFamiTF316115.

Enzyme and pathway databases

BioCyciZFISH:G66-33339-MONOMER.
ReactomeiR-HSA-1299344. TWIK-related spinal cord K+ channel (TRESK).
R-HSA-5576886. Phase 4 - resting membrane potential.

Miscellaneous databases

GeneWikiiKCNK18.
GenomeRNAii338567.
PROiQ7Z418.
SOURCEiSearch...

Gene expression databases

CleanExiHS_KCNK18.

Family and domain databases

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

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: November 2, 2016
This is version 113 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

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.