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Protein

Potassium channel subfamily K member 18

Gene

Kcnk18

Organism
Mus musculus (Mouse)
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.3 Publications

GO - Molecular functioni

GO - Biological processi

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_325523. 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 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:2685627. Kcnk18.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3131CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei32 – 5221HelicalSequence AnalysisAdd
BLAST
Intramembranei114 – 14027Pore-forming; Name=Pore-forming 1Sequence AnalysisAdd
BLAST
Transmembranei142 – 16221HelicalSequence AnalysisAdd
BLAST
Topological domaini163 – 292130CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei293 – 31321HelicalSequence AnalysisAdd
BLAST
Intramembranei326 – 34015Pore-forming; Name=Pore-forming 2Sequence AnalysisAdd
BLAST
Transmembranei347 – 36721HelicalSequence AnalysisAdd
BLAST
Topological domaini368 – 39427CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • integral component of plasma membrane Source: GO_Central
  • plasma membrane Source: UniProtKB
Complete GO annotation...

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.

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...

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

        10         20         30         40         50
MEAEEPPEAR RCCPEALGKA RGCCPEALGK LLPGLCFLCC LVTYALVGAA
60 70 80 90 100
LFSAVEGRPD PEAEENPELK KFLDDLCNIL KCNLTVVEGS RKNLCEHLQH
110 120 130 140 150
LKPQWLKAPQ DWSFLSALFF CCTVFSTVGY GHMYPVTRLG KFLCMLYALF
160 170 180 190 200
GIPLMFLVLT DIGDILATIL SRAYSRFQAL LCLPHDIFKW RSLPLCRKQP
210 220 230 240 250
DSKPVEEAIP QIVIDAGVDE LLNPQPSKDP PSPSCNVELF ERLVAREKKN
260 270 280 290 300
KLQPPTRPVE RSNSCPELVL GRLSCSILSN LDEVGQQVER LDIPLPVIAL
310 320 330 340 350
VVFAYISCAA AILPFWETEL GFEDAFYFCF VTLTTIGFGD IVLVHPHFFL
360 370 380 390
FFSIYIIVGM EILFIAFKLM QNRLLHTYKT LMLFVCQREV SLPW
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

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

Protein family/group databases

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

PTM databases

PhosphoSiteiQ6VV64.

Proteomic databases

PRIDEiQ6VV64.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi338567.
MGIiMGI:2685627. Kcnk18.

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiREACT_325523. TWIK-related spinal cord K+ channel (TRESK).

Miscellaneous databases

NextBioi399876.
PROiQ6VV64.
SOURCEiSearch...

Gene expression databases

BgeeiQ6VV64.
CleanExiMM_KCNK18.

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.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: June 24, 2015
This is version 99 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

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 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.