KCNKI_MOUSE
ID KCNKI_MOUSE Reviewed; 394 AA.
AC Q6VV64; Q1LZJ5; Q1LZM8; Q3MI50; Q3MI51;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Potassium channel subfamily K member 18;
DE AltName: Full=Two-pore-domain potassium channel TRESK;
GN Name=Kcnk18; Synonyms=Tresk-2, Tresk2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, MUTAGENESIS OF SER-276,
RP PHOSPHORYLATION AT SER-276, AND TISSUE SPECIFICITY.
RC STRAIN=NMRI; TISSUE=Cerebellum;
RX PubMed=14981085; DOI=10.1074/jbc.m312229200;
RA Czirjak G., Toth Z.E., Enyedi P.;
RT "The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic
RT calcium signal through calcineurin.";
RL J. Biol. Chem. 279:18550-18558(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND FUNCTION.
RC STRAIN=BALB/cJ; TISSUE=Spinal cord;
RX PubMed=16192517; DOI=10.1213/01.ane.0000168447.87557.5a;
RA Keshavaprasad B., Liu C., Au J.D., Kindler C.H., Cotten J.F., Yost C.S.;
RT "Species-specific differences in response to anesthetics and other
RT modulators by the K2P channel TRESK.";
RL Anesth. Analg. 101:1042-1049(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Egg;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH CALCINEURIN.
RX PubMed=16569637; DOI=10.1074/jbc.m602495200;
RA Czirjak G., Enyedi P.;
RT "Targeting of calcineurin to an NFAT-like docking site is required for the
RT calcium-dependent activation of the background K+ channel, TRESK.";
RL J. Biol. Chem. 281:14677-14682(2006).
RN [6]
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF HIS-132.
RX PubMed=17962323; DOI=10.1113/jphysiol.2007.145649;
RA Dobler T., Springauf A., Tovornik S., Weber M., Schmitt A., Sedlmeier R.,
RA Wischmeyer E., Doring F.;
RT "TRESK two-pore-domain K+ channels constitute a significant component of
RT background potassium currents in murine dorsal root ganglion neurones.";
RL J. Physiol. (Lond.) 585:867-879(2007).
RN [7]
RP INTERACTION WITH YWHAH, MUTAGENESIS OF SER-264, AND PHOSPHORYLATION AT
RP SER-264.
RX PubMed=18397886; DOI=10.1074/jbc.m800712200;
RA Czirjak G., Vuity D., Enyedi P.;
RT "Phosphorylation-dependent binding of 14-3-3 proteins controls TRESK
RT regulation.";
RL J. Biol. Chem. 283:15672-15680(2008).
RN [8]
RP FUNCTION.
RX PubMed=18568022; DOI=10.1038/nn.2143;
RA Bautista D.M., Sigal Y.M., Milstein A.D., Garrison J.L., Zorn J.A.,
RA Tsuruda P.R., Nicoll R.A., Julius D.;
RT "Pungent agents from Szechuan peppers excite sensory neurons by inhibiting
RT two-pore potassium channels.";
RL Nat. Neurosci. 11:772-779(2008).
RN [9]
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-83, AND MUTAGENESIS OF ASN-83.
RX PubMed=20006580; DOI=10.1016/j.bbrc.2009.12.056;
RA Egenberger B., Polleichtner G., Wischmeyer E., Doring F.;
RT "N-linked glycosylation determines cell surface expression of two-pore-
RT domain K+ channel TRESK.";
RL Biochem. Biophys. Res. Commun. 391:1262-1267(2010).
RN [10]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=20871611; DOI=10.1038/nm.2216;
RA Lafreniere R.G., Cader M.Z., Poulin J.F., Andres-Enguix I., Simoneau M.,
RA Gupta N., Boisvert K., Lafreniere F., McLaughlan S., Dube M.P.,
RA Marcinkiewicz M.M., Ramagopalan S., Ansorge O., Brais B., Sequeiros J.,
RA Pereira-Monteiro J.M., Griffiths L.R., Tucker S.J., Ebers G., Rouleau G.A.;
RT "A dominant-negative mutation in the TRESK potassium channel is linked to
RT familial migraine with aura.";
RL Nat. Med. 16:1157-1160(2010).
CC -!- FUNCTION: Outward rectifying potassium channel. Produces rapidly
CC activating outward rectifier K(+) currents. May function as background
CC potassium channel that sets the resting membrane potential. Channel
CC activity is directly activated by calcium signal. Activated by the
CC G(q)-protein coupled receptor pathway. The calcium signal robustly
CC activates the channel via calcineurin, whereas the anchoring of 14-3-
CC 3/YWHAH interferes with the return of the current to the resting state
CC after activation. Inhibited also by arachidonic acid and other
CC naturally occurring unsaturated free fatty acids. Channel activity is
CC also enhanced by volatile anesthetics, such as isoflurane. Appears to
CC be the primary target of hydroxy-alpha-sanshool, an ingredient of
CC Schezuan pepper. May be involved in the somatosensory function with
CC special respect to pain sensation. {ECO:0000269|PubMed:14981085,
CC ECO:0000269|PubMed:16192517, ECO:0000269|PubMed:18568022}.
CC -!- SUBUNIT: Interacts with calcineurin. Interacts with YWHAH, in a
CC phosphorylation-dependent manner. {ECO:0000269|PubMed:16569637,
CC ECO:0000269|PubMed:18397886}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20006580};
CC Multi-pass membrane protein {ECO:0000269|PubMed:20006580}.
CC -!- TISSUE SPECIFICITY: Detected in brain cortex, cerebellum, dorsal root
CC ganglion, spinal cord and testis. High expression in trigeminal
CC ganglion, also expressed in autonomic nervous system ganglia such as
CC the stellate ganglion and paravertebral sympathetic ganglia. Expressed
CC in all adult spinal cord and brain regions, with slightly higher
CC expression in thalamus, hypothalamus, hippocampus and posterior corte
CC (at protein level). In non-neuronal tissues, substantial expression
CC found in lung and heart and weal expression in liver, testis, kidney,
CC small intestine and spleen. {ECO:0000269|PubMed:14981085,
CC ECO:0000269|PubMed:16192517, ECO:0000269|PubMed:17962323,
CC ECO:0000269|PubMed:20871611}.
CC -!- DEVELOPMENTAL STAGE: Expression appears in trigeminal ganglion and
CC dorsal root ganglia from 15.5 dpc and increased through 18 dpc to reach
CC a peak in newborn mouse postnatal day 1. {ECO:0000269|PubMed:20871611}.
CC -!- PTM: Phosphorylation of Ser-264 is required for the binding of 14-3-
CC 3eta/YWHAH. Calcineurin-mediated dephosphorylation of Ser-276 enhances
CC channel activity. {ECO:0000269|PubMed:14981085,
CC ECO:0000269|PubMed:18397886}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:20006580}.
CC -!- MISCELLANEOUS: Regulated by extracellular protons whereas human
CC ortholog is not. His-132 is responsible for proton-dependent specific
CC activity.
CC -!- SIMILARITY: Belongs to the two pore domain potassium channel (TC
CC 1.A.1.8) family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Throb - Issue 124 of
CC December 2010;
CC URL="https://web.expasy.org/spotlight/back_issues/124";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY325301; AAQ91836.1; -; mRNA.
DR EMBL; AY542902; AAS48426.1; -; mRNA.
DR EMBL; AK139600; BAE24080.1; -; mRNA.
DR EMBL; AK162136; BAE36746.1; -; mRNA.
DR EMBL; BC104132; AAI04133.1; -; mRNA.
DR EMBL; BC104133; AAI04134.1; -; mRNA.
DR EMBL; BC115705; AAI15706.1; -; mRNA.
DR EMBL; BC115887; AAI15888.1; -; mRNA.
DR EMBL; BC127136; AAI27137.1; -; mRNA.
DR EMBL; BC127137; AAI27138.1; -; mRNA.
DR CCDS; CCDS29934.1; -.
DR RefSeq; NP_997144.1; NM_207261.3.
DR AlphaFoldDB; Q6VV64; -.
DR ELM; Q6VV64; -.
DR IntAct; Q6VV64; 1.
DR MINT; Q6VV64; -.
DR STRING; 10090.ENSMUSP00000065713; -.
DR TCDB; 1.A.1.18.1; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q6VV64; 1 site.
DR iPTMnet; Q6VV64; -.
DR PhosphoSitePlus; Q6VV64; -.
DR PaxDb; Q6VV64; -.
DR PRIDE; Q6VV64; -.
DR ABCD; Q6VV64; 1 sequenced antibody.
DR Antibodypedia; 46272; 113 antibodies from 29 providers.
DR DNASU; 332396; -.
DR Ensembl; ENSMUST00000065204; ENSMUSP00000065713; ENSMUSG00000040901.
DR GeneID; 332396; -.
DR KEGG; mmu:332396; -.
DR UCSC; uc008ibh.1; mouse.
DR CTD; 338567; -.
DR MGI; MGI:2685627; Kcnk18.
DR VEuPathDB; HostDB:ENSMUSG00000040901; -.
DR eggNOG; KOG1418; Eukaryota.
DR GeneTree; ENSGT00700000104522; -.
DR HOGENOM; CLU_022504_5_3_1; -.
DR InParanoid; Q6VV64; -.
DR OMA; FCCTVIS; -.
DR OrthoDB; 774951at2759; -.
DR PhylomeDB; Q6VV64; -.
DR TreeFam; TF316115; -.
DR Reactome; R-MMU-1299344; TWIK-related spinal cord K+ channel (TRESK).
DR Reactome; R-MMU-5576886; Phase 4 - resting membrane potential.
DR BioGRID-ORCS; 332396; 2 hits in 70 CRISPR screens.
DR PRO; PR:Q6VV64; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q6VV64; protein.
DR Bgee; ENSMUSG00000040901; Expressed in animal zygote and 3 other tissues.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0015269; F:calcium-activated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; ISO:MGI.
DR GO; GO:0022841; F:potassium ion leak channel activity; IBA:GO_Central.
DR GO; GO:0071467; P:cellular response to pH; ISO:MGI.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; ISO:MGI.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; IDA:UniProtKB.
DR GO; GO:0030322; P:stabilization of membrane potential; IBA:GO_Central.
DR InterPro; IPR003280; 2pore_dom_K_chnl.
DR InterPro; IPR003092; 2pore_dom_K_chnl_TASK.
DR InterPro; IPR013099; K_chnl_dom.
DR PANTHER; PTHR11003; PTHR11003; 1.
DR Pfam; PF07885; Ion_trans_2; 2.
DR PRINTS; PR01333; 2POREKCHANEL.
DR PRINTS; PR01095; TASKCHANNEL.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Potassium; Potassium channel; Potassium transport;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..394
FT /note="Potassium channel subfamily K member 18"
FT /id="PRO_0000312501"
FT TOPO_DOM 1..31
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 114..140
FT /note="Pore-forming; Name=Pore-forming 1"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..292
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 326..340
FT /note="Pore-forming; Name=Pore-forming 2"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..367
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 368..394
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 210..215
FT /note="Interaction with calcineurin"
FT REGION 261..266
FT /note="Interaction with YWHAH"
FT /evidence="ECO:0000269|PubMed:18397886"
FT MOD_RES 264
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18397886"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:14981085"
FT CARBOHYD 83
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20006580"
FT MUTAGEN 83
FT /note="N->Q: Strongly reduced current amplitude and
FT localization to cell membrane."
FT /evidence="ECO:0000269|PubMed:20006580"
FT MUTAGEN 132
FT /note="H->N: Insensitive to extracellular protons."
FT /evidence="ECO:0000269|PubMed:17962323"
FT MUTAGEN 212
FT /note="I->A: Loss of interaction with calcineurin and
FT activation by elevated intracellular calcium; when
FT associated with A-214."
FT MUTAGEN 214
FT /note="I->A: Strongly reduced activation by elevated
FT intracellular calcium. Loss of interaction with calcineurin
FT and activation by elevated intracellular calcium; when
FT associated with A-212."
FT MUTAGEN 264
FT /note="S->A: Loss of interaction with YWHAH."
FT /evidence="ECO:0000269|PubMed:18397886"
FT MUTAGEN 276
FT /note="S->A: Enhances basal channel activity and abolishes
FT stimulation by calcineurin."
FT /evidence="ECO:0000269|PubMed:14981085"
FT CONFLICT 228
FT /note="K -> R (in Ref. 4; AAI15706/AAI04133)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="K -> E (in Ref. 4; AAI15706/AAI04133)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 394 AA; 44403 MW; 82D03F7D7F0D5591 CRC64;
MEAEEPPEAR RCCPEALGKA RGCCPEALGK LLPGLCFLCC LVTYALVGAA LFSAVEGRPD
PEAEENPELK KFLDDLCNIL KCNLTVVEGS RKNLCEHLQH LKPQWLKAPQ DWSFLSALFF
CCTVFSTVGY GHMYPVTRLG KFLCMLYALF GIPLMFLVLT DIGDILATIL SRAYSRFQAL
LCLPHDIFKW RSLPLCRKQP DSKPVEEAIP QIVIDAGVDE LLNPQPSKDP PSPSCNVELF
ERLVAREKKN KLQPPTRPVE RSNSCPELVL GRLSCSILSN LDEVGQQVER LDIPLPVIAL
VVFAYISCAA AILPFWETEL GFEDAFYFCF VTLTTIGFGD IVLVHPHFFL FFSIYIIVGM
EILFIAFKLM QNRLLHTYKT LMLFVCQREV SLPW
