KCNK5_HUMAN
ID KCNK5_HUMAN Reviewed; 499 AA.
AC O95279; B2RAQ6; B5TJL2; Q5VV76;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Potassium channel subfamily K member 5 {ECO:0000305};
DE AltName: Full=Acid-sensitive potassium channel protein TASK-2;
DE AltName: Full=TWIK-related acid-sensitive K(+) channel 2;
GN Name=KCNK5 {ECO:0000312|HGNC:HGNC:6280}; Synonyms=TASK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=9812978; DOI=10.1074/jbc.273.47.30863;
RA Reyes R., Duprat F., Lesage F., Fink M., Salinas M., Farman N.,
RA Lazdunski M.;
RT "Cloning and expression of a novel pH-sensitive two pore domain K+ channel
RT from human kidney.";
RL J. Biol. Chem. 273:30863-30869(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=18516069; DOI=10.1038/bjp.2008.213;
RA Gierten J., Ficker E., Bloehs R., Schlomer K., Kathofer S., Scholz E.,
RA Zitron E., Kiesecker C., Bauer A., Becker R., Katus H.A., Karle C.A.,
RA Thomas D.;
RT "Regulation of two-pore-domain (K2P) potassium leak channels by the
RT tyrosine kinase inhibitor genistein.";
RL Br. J. Pharmacol. 154:1680-1690(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [7]
RP INTERCHAIN DISULFIDE BOND.
RX PubMed=12851074; DOI=10.1080/0968768031000084181;
RA Niemeyer M.I., Cid L.P., Valenzuela X., Paeile V., Sepulveda F.V.;
RT "Extracellular conserved cysteine forms an intersubunit disulphide bridge
RT in the KCNK5 (TASK-2) K+ channel without having an essential effect upon
RT activity.";
RL Mol. Membr. Biol. 20:185-191(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
CC -!- FUNCTION: pH-dependent, outwardly rectifying potassium channel
CC (PubMed:9812978). Outward rectification is lost at high external K(+)
CC concentrations (PubMed:9812978). {ECO:0000269|PubMed:9812978}.
CC -!- SUBUNIT: Homodimer; disulfide-linked.
CC -!- INTERACTION:
CC O95279; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-3934936, EBI-10827839;
CC O95279; Q6RW13-2: AGTRAP; NbExp=3; IntAct=EBI-3934936, EBI-11522760;
CC O95279; P29972: AQP1; NbExp=3; IntAct=EBI-3934936, EBI-745213;
CC O95279; P18859: ATP5PF; NbExp=3; IntAct=EBI-3934936, EBI-2606700;
CC O95279; Q12982: BNIP2; NbExp=3; IntAct=EBI-3934936, EBI-752094;
CC O95279; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-3934936, EBI-11522780;
CC O95279; P21964: COMT; NbExp=3; IntAct=EBI-3934936, EBI-372265;
CC O95279; O43169: CYB5B; NbExp=3; IntAct=EBI-3934936, EBI-1058710;
CC O95279; P29033: GJB2; NbExp=3; IntAct=EBI-3934936, EBI-3905204;
CC O95279; P24593: IGFBP5; NbExp=3; IntAct=EBI-3934936, EBI-720480;
CC O95279; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-3934936, EBI-2820517;
CC O95279; Q9Y2E5: MAN2B2; NbExp=3; IntAct=EBI-3934936, EBI-12243024;
CC O95279; Q8N138: ORMDL3; NbExp=3; IntAct=EBI-3934936, EBI-721750;
CC O95279; Q8N2U9: SLC66A2; NbExp=3; IntAct=EBI-3934936, EBI-3907610;
CC O95279; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-3934936, EBI-8640191;
CC O95279; P0DN84: STRIT1; NbExp=3; IntAct=EBI-3934936, EBI-12200293;
CC O95279; P48230: TM4SF4; NbExp=3; IntAct=EBI-3934936, EBI-8650934;
CC O95279; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-3934936, EBI-10694905;
CC O95279; Q9Y6G1: TMEM14A; NbExp=3; IntAct=EBI-3934936, EBI-2800360;
CC O95279; Q96HP8: TMEM176A; NbExp=3; IntAct=EBI-3934936, EBI-2800645;
CC O95279; A2RU14: TMEM218; NbExp=3; IntAct=EBI-3934936, EBI-10173151;
CC O95279; Q969K7: TMEM54; NbExp=3; IntAct=EBI-3934936, EBI-3922833;
CC O95279; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-3934936, EBI-2852148;
CC O95279; O14798: TNFRSF10C; NbExp=3; IntAct=EBI-3934936, EBI-717441;
CC O95279; Q86UF1: TSPAN33; NbExp=3; IntAct=EBI-3934936, EBI-12045841;
CC O95279; Q15836: VAMP3; NbExp=3; IntAct=EBI-3934936, EBI-722343;
CC O95279; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-3934936, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Abundant expression in kidney, also detected in
CC liver, placenta and small intestine. In the kidney, expression is
CC restricted to the distal tubules and collecting ducts (PubMed:9812978).
CC Not expressed in proximal tubules or glomeruli (PubMed:9812978).
CC {ECO:0000269|PubMed:9812978}.
CC -!- MISCELLANEOUS: Inhibited by quinine, quinidine and external
CC acidification. {ECO:0000269|PubMed:9812978}.
CC -!- SIMILARITY: Belongs to the two pore domain potassium channel (TC
CC 1.A.1.8) family. {ECO:0000305}.
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DR EMBL; AF084830; AAC79458.1; -; mRNA.
DR EMBL; EU978936; ACH86095.1; -; mRNA.
DR EMBL; AK314298; BAG36953.1; -; mRNA.
DR EMBL; AL451185; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03979.1; -; Genomic_DNA.
DR EMBL; BC060793; AAH60793.1; -; mRNA.
DR EMBL; BC069573; AAH69573.1; -; mRNA.
DR CCDS; CCDS4841.1; -.
DR RefSeq; NP_003731.1; NM_003740.3.
DR AlphaFoldDB; O95279; -.
DR SMR; O95279; -.
DR BioGRID; 114197; 31.
DR IntAct; O95279; 29.
DR STRING; 9606.ENSP00000352527; -.
DR BindingDB; O95279; -.
DR ChEMBL; CHEMBL4523157; -.
DR GuidetoPHARMACOLOGY; 517; -.
DR TCDB; 1.A.1.8.2; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; O95279; 1 site.
DR iPTMnet; O95279; -.
DR PhosphoSitePlus; O95279; -.
DR BioMuta; KCNK5; -.
DR EPD; O95279; -.
DR jPOST; O95279; -.
DR MassIVE; O95279; -.
DR MaxQB; O95279; -.
DR PaxDb; O95279; -.
DR PeptideAtlas; O95279; -.
DR PRIDE; O95279; -.
DR ProteomicsDB; 50787; -.
DR Antibodypedia; 15697; 110 antibodies from 29 providers.
DR DNASU; 8645; -.
DR Ensembl; ENST00000359534.4; ENSP00000352527.3; ENSG00000164626.9.
DR GeneID; 8645; -.
DR KEGG; hsa:8645; -.
DR MANE-Select; ENST00000359534.4; ENSP00000352527.3; NM_003740.4; NP_003731.1.
DR UCSC; uc003oon.4; human.
DR CTD; 8645; -.
DR DisGeNET; 8645; -.
DR GeneCards; KCNK5; -.
DR HGNC; HGNC:6280; KCNK5.
DR HPA; ENSG00000164626; Tissue enhanced (intestine, kidney).
DR MIM; 603493; gene.
DR neXtProt; NX_O95279; -.
DR OpenTargets; ENSG00000164626; -.
DR PharmGKB; PA30062; -.
DR VEuPathDB; HostDB:ENSG00000164626; -.
DR eggNOG; KOG1418; Eukaryota.
DR GeneTree; ENSGT00940000156775; -.
DR HOGENOM; CLU_040658_0_0_1; -.
DR InParanoid; O95279; -.
DR OMA; TEEWNYI; -.
DR OrthoDB; 1211599at2759; -.
DR PhylomeDB; O95279; -.
DR TreeFam; TF313947; -.
DR PathwayCommons; O95279; -.
DR Reactome; R-HSA-5576886; Phase 4 - resting membrane potential.
DR SignaLink; O95279; -.
DR BioGRID-ORCS; 8645; 22 hits in 1081 CRISPR screens.
DR ChiTaRS; KCNK5; human.
DR GeneWiki; KCNK5; -.
DR GenomeRNAi; 8645; -.
DR Pharos; O95279; Tchem.
DR PRO; PR:O95279; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O95279; protein.
DR Bgee; ENSG00000164626; Expressed in pancreatic ductal cell and 153 other tissues.
DR ExpressionAtlas; O95279; baseline and differential.
DR Genevisible; O95279; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0005267; F:potassium channel activity; IDA:GO_Central.
DR GO; GO:0022841; F:potassium ion leak channel activity; IBA:GO_Central.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; IDA:GO_Central.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0060075; P:regulation of resting membrane potential; ISS:ARUK-UCL.
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 Disulfide bond; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Potassium; Potassium channel; Potassium transport;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..499
FT /note="Potassium channel subfamily K member 5"
FT /id="PRO_0000101749"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 85..112
FT /note="Pore-forming; Name=Pore-forming 1"
FT /evidence="ECO:0000255"
FT TRANSMEM 113..133
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134..157
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 190..215
FT /note="Pore-forming; Name=Pore-forming 2"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..325
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 312..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..499
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51
FT /note="Interchain"
FT VARIANT 465
FT /note="P -> T (in dbSNP:rs9462487)"
FT /id="VAR_052425"
FT CONFLICT 423
FT /note="V -> A (in Ref. 3; BAG36953)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 499 AA; 55130 MW; E871A7A4823DDA00 CRC64;
MVDRGPLLTS AIIFYLAIGA AIFEVLEEPH WKEAKKNYYT QKLHLLKEFP CLGQEGLDKI
LEVVSDAAGQ GVAITGNQTF NNWNWPNAMI FAATVITTIG YGNVAPKTPA GRLFCVFYGL
FGVPLCLTWI SALGKFFGGR AKRLGQFLTK RGVSLRKAQI TCTVIFIVWG VLVHLVIPPF
VFMVTEGWNY IEGLYYSFIT ISTIGFGDFV AGVNPSANYH ALYRYFVELW IYLGLAWLSL
FVNWKVSMFV EVHKAIKKRR RRRKESFESS PHSRKALQVK GSTASKDVNI FSFLSKKEET
YNDLIKQIGK KAMKTSGGGE TGPGPGLGPQ GGGLPALPPS LVPLVVYSKN RVPTLEEVSQ
TLRSKGHVSR SPDEEAVARA PEDSSPAPEV FMNQLDRISE ECEPWDAQDY HPLIFQDASI
TFVNTEAGLS DEETSKSSLE DNLAGEESPQ QGAEAKAPLN MGEFPSSSES TFTSTESELS
VPYEQLMNEY NKANSPKGT
