Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q6VV64 (KCNKI_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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):
Two-pore-domain potassium channel TRESK
Gene names
Name:Kcnk18
Synonyms:Tresk-2, Tresk2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length394 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. Ref.1 Ref.2 Ref.8

Subunit structure

Interacts with calcineurin. Interacts with YWHAH, in a phosphorylation-dependent manner. Ref.5 Ref.7

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.9.

Tissue specificity

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. Ref.1 Ref.2 Ref.6 Ref.10

Developmental stage

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. Ref.10

Post-translational modification

Phosphorylation of Ser-264 is required for the binding of 14-3-3eta/YWHAH. Calcineurin-mediated dephosphorylation of Ser-276 enhances channel activity.

N-glycosylated. Ref.9

Miscellaneous

Regulated by extracellular protons whereas human ortholog is not. His-132 is responsible for proton-dependent specific activity.

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 – 394394Potassium channel subfamily K member 18
PRO_0000312501

Regions

Topological domain1 – 3131Cytoplasmic Potential
Transmembrane32 – 5221Helical; Potential
Intramembrane114 – 14027Pore-forming; Name=Pore-forming 1; Potential
Transmembrane142 – 16221Helical; Potential
Topological domain163 – 292130Cytoplasmic Potential
Transmembrane293 – 31321Helical; Potential
Intramembrane326 – 34015Pore-forming; Name=Pore-forming 2; Potential
Transmembrane347 – 36721Helical; Potential
Topological domain368 – 39427Cytoplasmic Potential
Region210 – 2156Interaction with calcineurin
Region261 – 2666Interaction with YWHAH

Amino acid modifications

Modified residue2641Phosphoserine Ref.7
Modified residue2761Phosphoserine Probable
Glycosylation831N-linked (GlcNAc...) Ref.9

Experimental info

Mutagenesis831N → Q: Strongly reduced current amplitude and localization to cell membrane. Ref.9
Mutagenesis1321H → N: Insensitive to extracellular protons. Ref.6
Mutagenesis2121I → A: Loss of interaction with calcineurin and activation by elevated intracellular calcium; when associated with A-214.
Mutagenesis2141I → A: Strongly reduced activation by elevated intracellular calcium. Loss of interaction with calcineurin and activation by elevated intracellular calcium; when associated with A-212.
Mutagenesis2641S → A: Loss of interaction with YWHAH. Ref.7
Mutagenesis2761S → A: Enhances basal channel activity and abolishes stimulation by calcineurin. Ref.1
Sequence conflict2281K → R in AAI15706. Ref.4
Sequence conflict2281K → R in AAI04133. Ref.4
Sequence conflict2511K → E in AAI15706. Ref.4
Sequence conflict2511K → E in AAI04133. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q6VV64 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 82D03F7D7F0D5591

FASTA39444,403
        10         20         30         40         50         60 
MEAEEPPEAR RCCPEALGKA RGCCPEALGK LLPGLCFLCC LVTYALVGAA LFSAVEGRPD 

        70         80         90        100        110        120 
PEAEENPELK KFLDDLCNIL KCNLTVVEGS RKNLCEHLQH LKPQWLKAPQ DWSFLSALFF 

       130        140        150        160        170        180 
CCTVFSTVGY GHMYPVTRLG KFLCMLYALF GIPLMFLVLT DIGDILATIL SRAYSRFQAL 

       190        200        210        220        230        240 
LCLPHDIFKW RSLPLCRKQP DSKPVEEAIP QIVIDAGVDE LLNPQPSKDP PSPSCNVELF 

       250        260        270        280        290        300 
ERLVAREKKN KLQPPTRPVE RSNSCPELVL GRLSCSILSN LDEVGQQVER LDIPLPVIAL 

       310        320        330        340        350        360 
VVFAYISCAA AILPFWETEL GFEDAFYFCF VTLTTIGFGD IVLVHPHFFL FFSIYIIVGM 

       370        380        390 
EILFIAFKLM QNRLLHTYKT LMLFVCQREV SLPW 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"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, DEVELOPMENTAL STAGE.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Throb - Issue 124 of December 2010

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS29934.1.
RefSeqNP_997144.1. NM_207261.3.
UniGeneMm.329947.

3D structure databases

ProteinModelPortalQ6VV64.
SMRQ6VV64. Positions 44-181.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ6VV64. 1 interaction.
MINTMINT-7997383.
STRING10090.ENSMUSP00000065713.

Protein family/group databases

TCDB1.A.1.18.1. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteQ6VV64.

Proteomic databases

PRIDEQ6VV64.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000065204; ENSMUSP00000065713; ENSMUSG00000040901.
GeneID332396.
KEGGmmu:332396.
UCSCuc008ibh.1. mouse.

Organism-specific databases

CTD338567.
MGIMGI:2685627. Kcnk18.

Phylogenomic databases

eggNOGNOG311880.
GeneTreeENSGT00700000104522.
HOGENOMHOG000074045.
HOVERGENHBG104673.
InParanoidQ6VV64.
OMAAFKLVQN.
OrthoDBEOG7MPRDX.
PhylomeDBQ6VV64.
TreeFamTF316115.

Gene expression databases

BgeeQ6VV64.
CleanExMM_KCNK18.
GenevestigatorQ6VV64.

Family and domain databases

InterProIPR003280. 2pore_dom_K_chnl.
IPR013099. 2pore_dom_K_chnl_dom.
IPR003092. 2pore_dom_K_chnl_TASK.
[Graphical view]
PfamPF07885. Ion_trans_2. 2 hits.
[Graphical view]
PRINTSPR01333. 2POREKCHANEL.
PR01095. TASKCHANNEL.
ProtoNetSearch...

Other

NextBio399876.
PROQ6VV64.
SOURCESearch...

Entry information

Entry nameKCNKI_MOUSE
AccessionPrimary (citable) accession number: Q6VV64
Secondary accession number(s): Q1LZJ5 expand/collapse secondary AC list , Q1LZM8, Q3MI50, Q3MI51
Entry history
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot