ID KCNK1_HUMAN Reviewed; 336 AA. AC O00180; Q13307; Q5T5E8; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1997, sequence version 1. DT 27-MAR-2024, entry version 199. DE RecName: Full=Potassium channel subfamily K member 1; DE AltName: Full=Inward rectifying potassium channel protein TWIK-1 {ECO:0000303|PubMed:8605869}; DE AltName: Full=Potassium channel K2P1 {ECO:0000303|PubMed:15820677}; DE AltName: Full=Potassium channel KCNO1; GN Name=KCNK1; Synonyms=HOHO1 {ECO:0000303|PubMed:9462864}, KCNO1, TWIK1; 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, SUBCELLULAR LOCATION, MUTAGENESIS OF RP THR-161, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE RP SPECIFICITY. RC TISSUE=Kidney; RX PubMed=8605869; DOI=10.1002/j.1460-2075.1996.tb00437.x; RA Lesage F., Guillemare E., Fink M., Duprat F., Lazdunski M., Romey G., RA Barhanin J.; RT "TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a RT novel structure."; RL EMBO J. 15:1004-1011(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND REVIEW. RC TISSUE=Brain; RX PubMed=9462864; DOI=10.1007/s001090050186; RA Goldstein S.A.N., Wang K.-W., Ilan N., Pausch M.H.; RT "Sequence and function of the two P domain potassium channels: implications RT of an emerging superfamily."; RL J. Mol. Med. 76:13-20(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=9362344; DOI=10.1152/ajprenal.1997.273.4.f663; RA Orias M., Velazquez H., Tung F., Lee G., Desir G.V.; RT "Cloning and localization of a double-pore K channel, KCNK1: exclusive RT expression in distal nephron segments."; RL Am. J. Physiol. 273:F663-F666(1997). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). 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=Brain; 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 FUNCTION, SUBUNIT, DISULFIDE BOND, GLYCOSYLATION AT ASN-95, MUTAGENESIS OF RP CYS-69 AND ASN-95, SUBCELLULAR LOCATION, AND TOPOLOGY. RX PubMed=8978667; DOI=10.1002/j.1460-2075.1996.tb01031.x; RA Lesage F., Reyes R., Fink M., Duprat F., Guillemare E., Lazdunski M.; RT "Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge."; RL EMBO J. 15:6400-6407(1996). RN [8] RP TISSUE SPECIFICITY. RX PubMed=11165377; DOI=10.1016/s0169-328x(00)00263-1; RA Medhurst A.D., Rennie G., Chapman C.G., Meadows H., Duckworth M.D., RA Kelsell R.E., Gloger I.I., Pangalos M.N.; RT "Distribution analysis of human two pore domain potassium channels in RT tissues of the central nervous system and periphery."; RL Brain Res. Mol. Brain Res. 86:101-114(2001). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, SUMOYLATION AT LYS-274, MUTAGENESIS OF RP HIS-122 AND LYS-274, AND INTERACTION WITH UBE2I. RX PubMed=15820677; DOI=10.1016/j.cell.2005.01.019; RA Rajan S., Plant L.D., Rabin M.L., Butler M.H., Goldstein S.A.; RT "Sumoylation silences the plasma membrane leak K+ channel K2P1."; RL Cell 121:37-47(2005). RN [10] RP LACK OF SUMOYLATION AT LYS-274, MUTAGENESIS OF LYS-274, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=17693262; DOI=10.1016/j.cell.2007.06.012; RA Feliciangeli S., Bendahhou S., Sandoz G., Gounon P., Reichold M., Warth R., RA Lazdunski M., Barhanin J., Lesage F.; RT "Does sumoylation control K2P1/TWIK1 background K+ channels?"; RL Cell 130:563-569(2007). RN [11] RP TISSUE SPECIFICITY. RX PubMed=17478540; DOI=10.1113/jphysiol.2006.126714; RA Gaborit N., Le Bouter S., Szuts V., Varro A., Escande D., Nattel S., RA Demolombe S.; RT "Regional and tissue specific transcript signatures of ion channel genes in RT the non-diseased human heart."; RL J. Physiol. (Lond.) 582:675-693(2007). RN [12] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF LYS-274; 293-ILE-ILE-294 AND 299-LEU--HIS-336. RX PubMed=19959478; DOI=10.1074/jbc.m109.078535; RA Feliciangeli S., Tardy M.P., Sandoz G., Chatelain F.C., Warth R., RA Barhanin J., Bendahhou S., Lesage F.; RT "Potassium channel silencing by constitutive endocytosis and intracellular RT sequestration."; RL J. Biol. Chem. 285:4798-4805(2010). RN [13] RP SUMOYLATION AT LYS-274, MUTAGENESIS OF HIS-122 AND LYS-274, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=20498050; DOI=10.1073/pnas.1004712107; RA Plant L.D., Dementieva I.S., Kollewe A., Olikara S., Marks J.D., RA Goldstein S.A.; RT "One SUMO is sufficient to silence the dimeric potassium channel K2P1."; RL Proc. Natl. Acad. Sci. U.S.A. 107:10743-10748(2010). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-118 AND LYS-274, TISSUE RP SPECIFICITY, AND ACTIVITY REGULATION. RX PubMed=21653227; DOI=10.1126/scisignal.2001726; RA Ma L., Zhang X., Chen H.; RT "TWIK-1 two-pore domain potassium channels change ion selectivity and RT conduct inward leak sodium currents in hypokalemia."; RL Sci. Signal. 4:RA37-RA37(2011). RN [15] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=21964404; DOI=10.1152/ajplung.00102.2011; RA Zhao K.Q., Xiong G., Wilber M., Cohen N.A., Kreindler J.L.; RT "A role for two-pore K? channels in modulating Na? absorption and Cl? RT secretion in normal human bronchial epithelial cells."; RL Am. J. Physiol. 302:L4-L12(2012). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [17] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 108-LEU-PHE-109; RP THR-118; HIS-122; LEU-146; LEU-228; THR-250 AND LYS-274. RX PubMed=22431633; DOI=10.1073/pnas.1201132109; RA Chatelain F.C., Bichet D., Douguet D., Feliciangeli S., Bendahhou S., RA Reichold M., Warth R., Barhanin J., Lesage F.; RT "TWIK1, a unique background channel with variable ion selectivity."; RL Proc. Natl. Acad. Sci. U.S.A. 109:5499-5504(2012). RN [18] RP SUBCELLULAR LOCATION, FUNCTION, SUMOYLATION, INTERACTION WITH KCNK3 AND RP KCNK9, AND MUTAGENESIS OF TYR-231. RX PubMed=23169818; DOI=10.1126/scisignal.2003431; RA Plant L.D., Zuniga L., Araki D., Marks J.D., Goldstein S.A.; RT "SUMOylation silences heterodimeric TASK potassium channels containing K2P1 RT subunits in cerebellar granule neurons."; RL Sci. Signal. 5:RA84-RA84(2012). RN [19] RP REVIEW. RX PubMed=25530075; DOI=10.1113/jphysiol.2014.287268; RA Feliciangeli S., Chatelain F.C., Bichet D., Lesage F.; RT "The family of K2P channels: salient structural and functional RT properties."; RL J. Physiol. (Lond.) 593:2587-2603(2015). RN [20] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-146 AND LEU-261, AND RP SITE. RX PubMed=25001086; DOI=10.1038/ncomms5377; RA Aryal P., Abd-Wahab F., Bucci G., Sansom M.S., Tucker S.J.; RT "A hydrophobic barrier deep within the inner pore of the TWIK-1 K2P RT potassium channel."; RL Nat. Commun. 5:4377-4377(2014). RN [21] RP REVIEW. RX PubMed=25339226; DOI=10.1007/s00424-014-1631-y; RA Bichet D., Blin S., Feliciangeli S., Chatelain F.C., Bobak N., Lesage F.; RT "Silent but not dumb: how cellular trafficking and pore gating modulate RT expression of TWIK1 and THIK2."; RL Pflugers Arch. 467:1121-1131(2015). RN [22] RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 23-288 IN COMPLEX WITH POTASSIUM RP IONS, FUNCTION, SUBUNIT, DISULFIDE BOND, TOPOLOGY, AND SUBCELLULAR RP LOCATION. RX PubMed=22282804; DOI=10.1126/science.1213274; RA Miller A.N., Long S.B.; RT "Crystal structure of the human two-pore domain potassium channel K2P1."; RL Science 335:432-436(2012). CC -!- FUNCTION: Ion channel that contributes to passive transmembrane CC potassium transport and to the regulation of the resting membrane CC potential in brain astrocytes, but also in kidney and in other tissues CC (PubMed:15820677, PubMed:21653227). Forms dimeric channels through CC which potassium ions pass in accordance with their electrochemical CC gradient. The channel is selective for K(+) ions at physiological CC potassium concentrations and at neutral pH, but becomes permeable to CC Na(+) at subphysiological K(+) levels and upon acidification of the CC extracellular medium (PubMed:21653227, PubMed:22431633). The homodimer CC has very low potassium channel activity, when expressed in heterologous CC systems, and can function as weakly inward rectifying potassium channel CC (PubMed:8605869, PubMed:8978667, PubMed:15820677, PubMed:21653227, CC PubMed:22431633, PubMed:23169818, PubMed:25001086). Channel activity is CC modulated by activation of serotonin receptors (By similarity). CC Heterodimeric channels containing KCNK1 and KCNK2 have much higher CC activity, and may represent the predominant form in astrocytes (By CC similarity). Heterodimeric channels containing KCNK1 and KCNK3 or KCNK9 CC have much higher activity (PubMed:23169818). Heterodimeric channels CC formed by KCNK1 and KCNK9 may contribute to halothane-sensitive CC currents (PubMed:23169818). Mediates outward rectifying potassium CC currents in dentate gyrus granule cells and contributes to the CC regulation of their resting membrane potential (By similarity). CC Contributes to the regulation of action potential firing in dentate CC gyrus granule cells and down-regulates their intrinsic excitability (By CC similarity). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 CC is required for rapid glutamate release in response to activation of G- CC protein coupled receptors, such as F2R and CNR1 (By similarity). CC Required for normal ion and water transport in the kidney (By CC similarity). Contributes to the regulation of the resting membrane CC potential of pancreatic beta cells (By similarity). The low channel CC activity of homodimeric KCNK1 may be due to sumoylation CC (PubMed:15820677, PubMed:20498050, PubMed:23169818). The low channel CC activity may be due to rapid internalization from the cell membrane and CC retention in recycling endosomes (PubMed:19959478). CC {ECO:0000250|UniProtKB:O08581, ECO:0000250|UniProtKB:Q9Z2T2, CC ECO:0000269|PubMed:15820677, ECO:0000269|PubMed:17693262, CC ECO:0000269|PubMed:19959478, ECO:0000269|PubMed:20498050, CC ECO:0000269|PubMed:21653227, ECO:0000269|PubMed:22282804, CC ECO:0000269|PubMed:22431633, ECO:0000269|PubMed:23169818, CC ECO:0000269|PubMed:25001086, ECO:0000269|PubMed:8605869, CC ECO:0000269|PubMed:8978667}. CC -!- ACTIVITY REGULATION: Inhibited by Ba(2+) ions and quinidine CC (PubMed:8605869). Inhibited by quinine (PubMed:8605869, CC PubMed:21653227). Is slightly inhibited by 10 mM tetraethylammonium CC (TEA), and only marginally inhibited by 4-aminopyridine, charybdotoxin CC and dendrotoxin (PubMed:8605869). Lowering the extracellular pH to CC below 6.5 transiently activates the channel, and then inhibits channel CC activity (PubMed:15820677, PubMed:22431633). Inhibited when the CC intracellular pH is decreased down to pH 6.0, but this may be due to CC indirect effects (PubMed:8605869). {ECO:0000269|PubMed:15820677, CC ECO:0000269|PubMed:21653227, ECO:0000269|PubMed:22431633, CC ECO:0000269|PubMed:8605869}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC Note=Has a unit conductance of 34 pS. Both activation and channel CC closure are very rapid. Is not voltage-gated. The relationship CC between voltage and current is nearly linear. Has a mean open time of CC 0.3 msec at a membrane potential of -80 mV, and 1.9 msec at +80 mV CC (PubMed:8605869). {ECO:0000269|PubMed:19959478, CC ECO:0000269|PubMed:8605869}; CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:8978667, PubMed:22282804). CC Heterodimer with KCNK2; disulfide-linked (By similarity). In CC astrocytes, forms mostly heterodimeric potassium channels with KCNK2, CC with only a minor proportion of functional channels containing CC homodimeric KCNK1 (By similarity). Interacts with KCNK3 and KCNK9, CC forming functional heterodimeric channels (PubMed:23169818). Interacts CC with GNG4 (By similarity). Identified in a complex with PSD and ARF6; CC interacts only with PSD that is bound to ARF6 (By similarity). CC Interacts with UBE2I (PubMed:15820677). {ECO:0000250|UniProtKB:O08581, CC ECO:0000269|PubMed:15820677, ECO:0000269|PubMed:22282804, CC ECO:0000269|PubMed:23169818, ECO:0000269|PubMed:8978667}. CC -!- INTERACTION: CC O00180; Q13520: AQP6; NbExp=3; IntAct=EBI-3914675, EBI-13059134; CC O00180; O14735: CDIPT; NbExp=3; IntAct=EBI-3914675, EBI-358858; CC O00180; Q96BA8: CREB3L1; NbExp=5; IntAct=EBI-3914675, EBI-6942903; CC O00180; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-3914675, EBI-781551; CC O00180; O00180: KCNK1; NbExp=2; IntAct=EBI-3914675, EBI-3914675; CC O00180; P27105: STOM; NbExp=3; IntAct=EBI-3914675, EBI-1211440; CC O00180; P63165: SUMO1; NbExp=3; IntAct=EBI-3914675, EBI-80140; CC O00180; Q8IV31: TMEM139; NbExp=3; IntAct=EBI-3914675, EBI-7238458; CC O00180; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-3914675, EBI-8638294; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15820677, CC ECO:0000269|PubMed:17693262, ECO:0000269|PubMed:20498050, CC ECO:0000269|PubMed:21653227, ECO:0000269|PubMed:22282804, CC ECO:0000269|PubMed:22431633, ECO:0000269|PubMed:23169818, CC ECO:0000269|PubMed:25001086, ECO:0000269|PubMed:8605869, CC ECO:0000269|PubMed:8978667}; Multi-pass membrane protein CC {ECO:0000269|PubMed:22282804, ECO:0000269|PubMed:8978667, ECO:0000305}. CC Recycling endosome {ECO:0000269|PubMed:19959478}. Synaptic cell CC membrane {ECO:0000250|UniProtKB:Q9Z2T2}. Cytoplasmic vesicle CC {ECO:0000250|UniProtKB:O08581}. Perikaryon CC {ECO:0000250|UniProtKB:O08581}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:O08581}. Cell projection CC {ECO:0000250|UniProtKB:O08581}. Apical cell membrane CC {ECO:0000269|PubMed:21964404}; Multi-pass membrane protein CC {ECO:0000305}. Note=The heterodimer with KCNK2 is detected at the CC astrocyte cell membrane. Not detected at the astrocyte cell membrane CC when KCNK2 is absent. Detected on neuronal cell bodies, and to a lesser CC degree on neuronal cell projections. Detected on hippocampus dentate CC gyrus granule cell bodies and to a lesser degree on proximal dendrites. CC Detected at the apical cell membrane in stria vascularis in the CC cochlea. Detected at the apical cell membrane of vestibular dark cells CC situated between the crista and the utricle in the inner ear. Detected CC at the apical cell membrane in kidney proximal tubule segment S1 and in CC subapical compartments in segments S1, S2 and S3. Predominantly in CC cytoplasmic structures in kidney distal convoluted tubules and CC collecting ducts (By similarity). Detected at the apical cell membrane CC of bronchial epithelial cells (PubMed:21964404). CC {ECO:0000250|UniProtKB:O08581, ECO:0000250|UniProtKB:Q9Z2T2, CC ECO:0000269|PubMed:21964404}. CC -!- TISSUE SPECIFICITY: Detected in bronchial epithelial cells CC (PubMed:21964404). Detected in heart left atrium and left ventricle CC (PubMed:17478540). Detected in cardiac myocytes (at protein level) CC (PubMed:21653227). Widely expressed with high levels in heart, brain CC and kidney, and lower levels in colon, ovary, placenta, lung and liver CC (PubMed:8605869, PubMed:9362344). Highly expressed in cerebellum, and CC detected at lower levels in amygdala, caudate nucleus, brain cortex, CC hippocampus, putamen, substantia nigra, thalamus, dorsal root ganglion, CC spinal cord, pituitary, heart, kidney, lung, placenta, pancreas, CC stomach, small intestine, uterus and prostate (PubMed:11165377). CC Detected in right and left heart ventricle and atrium, and in heart CC Purkinje fibers (PubMed:17478540). {ECO:0000269|PubMed:11165377, CC ECO:0000269|PubMed:17478540, ECO:0000269|PubMed:21653227, CC ECO:0000269|PubMed:21964404, ECO:0000269|PubMed:8605869, CC ECO:0000269|PubMed:9362344}. CC -!- PTM: Sumoylation is controversial. Sumoylated by UBE2I CC (PubMed:15820677). Not sumoylated when expressed in xenopus oocytes or CC mammalian cells (PubMed:17693262). Sumoylation inactivates the channel, CC but does not interfere with expression at the cell membrane CC (PubMed:15820677). Sumoylation of a single subunit is sufficient to CC silence the dimeric channel (PubMed:20498050, PubMed:23169818). CC Sumoylation of KCNK1 is sufficient to silence heterodimeric channels CC formed by KCNK1 and KCNK3 or KCNK9 (PubMed:23169818). Desumoylated by CC SENP1; this activates the channel (PubMed:15820677, PubMed:20498050, CC PubMed:23169818). Desumoylated by SENP1; this strongly increases CC halothane-mediated activation of heterodimeric channels formed with CC KCNK9 (PubMed:23169818). SENP1 treatment has no effect CC (PubMed:17693262). {ECO:0000269|PubMed:15820677, CC ECO:0000269|PubMed:17693262, ECO:0000269|PubMed:20498050, CC ECO:0000269|PubMed:23169818}. CC -!- MISCELLANEOUS: When the external K(+) concentration is lowered to CC subphysiological levels, it takes several minutes till the channel has CC reached a new, stable state characterized by increased Na(+) CC permeability (PubMed:21653227). Likewise, when the external pH is CC lowered to values below 6.5, it takes several minutes till the channel CC has reached a new, stable state characterized by increased Na(+) CC permeability (PubMed:22431633). When raising the K(+) concentration CC back to 5 mM, it takes 40 to 70 minutes for the channel to regain its CC original selectivity for K(+) (PubMed:21653227). Likewise, it takes CC more that 25 minutes for the channel to regain its original K(+) CC selectivity when the pH is raised back to 7.4 (PubMed:22431633). CC {ECO:0000269|PubMed:21653227, ECO:0000269|PubMed:22431633}. CC -!- SIMILARITY: Belongs to the two pore domain potassium channel CC (TC 1.A.1.8) family. {ECO:0000305}. 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; U33632; AAB01688.1; -; mRNA. DR EMBL; U76996; AAB97878.1; -; mRNA. DR EMBL; U90065; AAB51147.1; -; mRNA. DR EMBL; AL356357; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471098; EAW69989.1; -; Genomic_DNA. DR EMBL; BC018051; AAH18051.1; -; mRNA. DR CCDS; CCDS1599.1; -. DR PIR; S65566; S65566. DR RefSeq; NP_002236.1; NM_002245.3. DR PDB; 3UKM; X-ray; 3.40 A; A/B/C/D=19-288. DR PDBsum; 3UKM; -. DR AlphaFoldDB; O00180; -. DR SMR; O00180; -. DR BioGRID; 109976; 83. DR DIP; DIP-59532N; -. DR IntAct; O00180; 11. DR STRING; 9606.ENSP00000355580; -. DR DrugBank; DB00308; Ibutilide. DR DrugBank; DB00908; Quinidine. DR DrugBank; DB01346; Quinidine barbiturate. DR GlyCosmos; O00180; 1 site, No reported glycans. DR GlyGen; O00180; 1 site. DR iPTMnet; O00180; -. DR PhosphoSitePlus; O00180; -. DR SwissPalm; O00180; -. DR BioMuta; KCNK1; -. DR EPD; O00180; -. DR jPOST; O00180; -. DR MassIVE; O00180; -. DR MaxQB; O00180; -. DR PaxDb; 9606-ENSP00000355580; -. DR PeptideAtlas; O00180; -. DR ProteomicsDB; 47763; -. DR Pumba; O00180; -. DR Antibodypedia; 20802; 335 antibodies from 32 providers. DR DNASU; 3775; -. DR Ensembl; ENST00000366621.8; ENSP00000355580.3; ENSG00000135750.15. DR GeneID; 3775; -. DR KEGG; hsa:3775; -. DR MANE-Select; ENST00000366621.8; ENSP00000355580.3; NM_002245.4; NP_002236.1. DR UCSC; uc010pxo.1; human. DR AGR; HGNC:6272; -. DR CTD; 3775; -. DR DisGeNET; 3775; -. DR GeneCards; KCNK1; -. DR HGNC; HGNC:6272; KCNK1. DR HPA; ENSG00000135750; Tissue enhanced (brain, choroid plexus). DR MIM; 601745; gene. DR neXtProt; NX_O00180; -. DR OpenTargets; ENSG00000135750; -. DR PharmGKB; PA219; -. DR VEuPathDB; HostDB:ENSG00000135750; -. DR eggNOG; KOG1418; Eukaryota. DR GeneTree; ENSGT00940000155293; -. DR HOGENOM; CLU_022504_6_0_1; -. DR InParanoid; O00180; -. DR OMA; SAWCFGL; -. DR OrthoDB; 600333at2759; -. DR PhylomeDB; O00180; -. DR TreeFam; TF313947; -. DR PathwayCommons; O00180; -. DR Reactome; R-HSA-1299308; Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK). DR Reactome; R-HSA-5576886; Phase 4 - resting membrane potential. DR SignaLink; O00180; -. DR BioGRID-ORCS; 3775; 13 hits in 1154 CRISPR screens. DR ChiTaRS; KCNK1; human. DR GeneWiki; KCNK1; -. DR GenomeRNAi; 3775; -. DR Pharos; O00180; Tbio. DR PRO; PR:O00180; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O00180; Protein. DR Bgee; ENSG00000135750; Expressed in cerebellar vermis and 195 other cell types or tissues. DR ExpressionAtlas; O00180; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:1902937; C:inward rectifier potassium channel complex; IEA:Ensembl. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0034705; C:potassium channel complex; IDA:UniProtKB. DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell. DR GO; GO:0097060; C:synaptic membrane; IEA:UniProtKB-SubCell. DR GO; GO:0008076; C:voltage-gated potassium channel complex; TAS:ProtInc. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005242; F:inward rectifier potassium channel activity; TAS:ProtInc. DR GO; GO:0015271; F:outward rectifier potassium channel activity; IBA:GO_Central. DR GO; GO:0005267; F:potassium channel activity; IDA:UniProtKB. DR GO; GO:0022841; F:potassium ion leak channel activity; IDA:UniProtKB. DR GO; GO:0005272; F:sodium channel activity; IDA:UniProtKB. DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc. DR GO; GO:0060075; P:regulation of resting membrane potential; IMP:UniProtKB. DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl. DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0030322; P:stabilization of membrane potential; IBA:GO_Central. DR Gene3D; 1.10.287.70; -; 1. DR InterPro; IPR003280; 2pore_dom_K_chnl. DR InterPro; IPR003092; 2pore_dom_K_chnl_TASK. DR InterPro; IPR005408; 2pore_dom_K_chnl_TWIK. DR InterPro; IPR001779; 2pore_dom_K_chnl_TWIK1. DR InterPro; IPR013099; K_chnl_dom. DR PANTHER; PTHR11003:SF59; POTASSIUM CHANNEL SUBFAMILY K MEMBER 1; 1. DR PANTHER; PTHR11003; POTASSIUM CHANNEL, SUBFAMILY K; 1. DR Pfam; PF07885; Ion_trans_2; 2. DR PIRSF; PIRSF038061; K_channel_subfamily_K_type; 1. DR PRINTS; PR01333; 2POREKCHANEL. DR PRINTS; PR01096; TWIK1CHANNEL. DR PRINTS; PR01586; TWIKCHANNEL. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 2. DR Genevisible; O00180; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Cell projection; Cytoplasmic vesicle; KW Disulfide bond; Endosome; Glycoprotein; Ion channel; Ion transport; KW Isopeptide bond; Membrane; Phosphoprotein; Potassium; Potassium channel; KW Potassium transport; Reference proteome; Synapse; Transmembrane; KW Transmembrane helix; Transport; Ubl conjugation. FT CHAIN 1..336 FT /note="Potassium channel subfamily K member 1" FT /id="PRO_0000101740" FT TOPO_DOM 1..20 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:22282804" FT TRANSMEM 21..41 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:22282804" FT TOPO_DOM 42..103 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:22282804, FT ECO:0000305|PubMed:8978667" FT INTRAMEM 104..116 FT /note="Helical; Name=Pore helix 1" FT /evidence="ECO:0000269|PubMed:22282804" FT INTRAMEM 117..122 FT /evidence="ECO:0000269|PubMed:22282804" FT TOPO_DOM 123..132 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:22282804" FT TRANSMEM 133..156 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:22282804" FT TOPO_DOM 157..181 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:22282804" FT TRANSMEM 182..202 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:22282804" FT TOPO_DOM 203..211 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:22282804" FT INTRAMEM 212..224 FT /note="Helical; Name=Pore helix 2" FT /evidence="ECO:0000269|PubMed:22282804" FT INTRAMEM 225..231 FT /evidence="ECO:0000269|PubMed:22282804" FT TOPO_DOM 232..243 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:22282804" FT TRANSMEM 244..267 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:22282804" FT TOPO_DOM 268..336 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:22282804" FT REGION 117..122 FT /note="Selectivity filter 1" FT /evidence="ECO:0000269|PubMed:22282804, FT ECO:0000305|PubMed:21653227" FT REGION 225..230 FT /note="Selectivity filter 2" FT /evidence="ECO:0000269|PubMed:22282804" FT REGION 293..299 FT /note="Important for intracellular retention in recycling FT endosomes" FT /evidence="ECO:0000269|PubMed:19959478" FT SITE 118 FT /note="Important for increased permeability to Na(+) when FT K(+) levels are subphysiological" FT /evidence="ECO:0000269|PubMed:21653227" FT SITE 146 FT /note="Part of a hydrophobic barrier that is stochastically FT dewetted and limits ion permeability" FT /evidence="ECO:0000269|PubMed:22431633, FT ECO:0000269|PubMed:25001086" FT SITE 261 FT /note="Part of a hydrophobic barrier that is stochastically FT dewetted and limits ion permeability" FT /evidence="ECO:0000269|PubMed:25001086" FT MOD_RES 326 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z2T2" FT CARBOHYD 95 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:8978667" FT DISULFID 69 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:22282804, FT ECO:0000269|PubMed:8978667" FT CROSSLNK 274 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:15820677, FT ECO:0000269|PubMed:20498050" FT MUTAGEN 69 FT /note="C->A: Abolishes channel activity and formation of FT disulfide-linked homodimers." FT /evidence="ECO:0000269|PubMed:8978667" FT MUTAGEN 95 FT /note="N->A: Abolishes N-glycosylation." FT /evidence="ECO:0000269|PubMed:8978667" FT MUTAGEN 108..109 FT /note="LF->FY: Impairs selectivity for K(+) ions and FT increases permeability to Na(+) ions, both at pH 7.4 and at FT pH 6." FT /evidence="ECO:0000269|PubMed:22431633" FT MUTAGEN 118 FT /note="T->I: Abolishes change in ion selectivity in the FT presence of subphysiological K(+) levels." FT /evidence="ECO:0000269|PubMed:21653227" FT MUTAGEN 122 FT /note="H->K: Increases channel activity, and has only a FT minor effect on the inhibition by acidification of the FT extracellular medium." FT /evidence="ECO:0000269|PubMed:22431633" FT MUTAGEN 122 FT /note="H->N: Decreases channel activity and abolishes FT inhibition by acidification of the extracellular medium." FT /evidence="ECO:0000269|PubMed:15820677, FT ECO:0000269|PubMed:20498050, ECO:0000269|PubMed:22431633" FT MUTAGEN 146 FT /note="L->A,V: Does not increase the low intrinsic channel FT activity." FT /evidence="ECO:0000269|PubMed:25001086" FT MUTAGEN 146 FT /note="L->D: Increases channel activity." FT /evidence="ECO:0000269|PubMed:22431633, FT ECO:0000269|PubMed:25001086" FT MUTAGEN 146 FT /note="L->N,T: Increases channel activity." FT /evidence="ECO:0000269|PubMed:25001086" FT MUTAGEN 146 FT /note="L->S: Increases channel activity. Strongly increases FT channel activity; when associated with S-261." FT /evidence="ECO:0000269|PubMed:25001086" FT MUTAGEN 161 FT /note="T->A: No effect on channel activity." FT /evidence="ECO:0000269|PubMed:8605869" FT MUTAGEN 228 FT /note="L->F: No effect on selectivity for K(+) ions." FT /evidence="ECO:0000269|PubMed:22431633" FT MUTAGEN 231 FT /note="Y->F: Strongly decreases activity of homodimeric FT channels and of heterodimeric channels formed with KCNK3 FT and with KCNK9. No effect on location at the cell FT membrane." FT /evidence="ECO:0000269|PubMed:23169818" FT MUTAGEN 250 FT /note="T->L: Slightly decreases the increased permeability FT to Na(+) ions at pH 6." FT /evidence="ECO:0000269|PubMed:22431633" FT MUTAGEN 261 FT /note="L->D,N: Increases channel activity." FT /evidence="ECO:0000269|PubMed:25001086" FT MUTAGEN 261 FT /note="L->S: Increases channel activity. Strongly increases FT channel activity; when associated with S-146." FT /evidence="ECO:0000269|PubMed:25001086" FT MUTAGEN 274 FT /note="K->A,C,D,Q,R: Converts the electrically silent FT channel that is present at the cell membrane to an active FT channel." FT /evidence="ECO:0000269|PubMed:20498050" FT MUTAGEN 274 FT /note="K->E: Converts the electrically silent channel that FT is present at the cell membrane to an active channel. No FT effect on retention in recycling endosomes." FT /evidence="ECO:0000269|PubMed:15820677, FT ECO:0000269|PubMed:17693262, ECO:0000269|PubMed:19959478, FT ECO:0000269|PubMed:20498050, ECO:0000269|PubMed:21653227, FT ECO:0000269|PubMed:22431633" FT MUTAGEN 293..294 FT /note="II->AA: Strongly increases location at the cell FT membrane." FT /evidence="ECO:0000269|PubMed:19959478" FT MUTAGEN 299..336 FT /note="Missing: No effect on intracellular retention in FT recycling endosomes." FT /evidence="ECO:0000269|PubMed:19959478" FT HELIX 19..66 FT /evidence="ECO:0007829|PDB:3UKM" FT HELIX 72..86 FT /evidence="ECO:0007829|PDB:3UKM" FT TURN 87..89 FT /evidence="ECO:0007829|PDB:3UKM" FT HELIX 104..115 FT /evidence="ECO:0007829|PDB:3UKM" FT HELIX 128..160 FT /evidence="ECO:0007829|PDB:3UKM" FT TURN 163..167 FT /evidence="ECO:0007829|PDB:3UKM" FT HELIX 177..195 FT /evidence="ECO:0007829|PDB:3UKM" FT HELIX 197..206 FT /evidence="ECO:0007829|PDB:3UKM" FT STRAND 207..209 FT /evidence="ECO:0007829|PDB:3UKM" FT HELIX 212..223 FT /evidence="ECO:0007829|PDB:3UKM" FT STRAND 236..238 FT /evidence="ECO:0007829|PDB:3UKM" FT HELIX 242..268 FT /evidence="ECO:0007829|PDB:3UKM" FT HELIX 271..278 FT /evidence="ECO:0007829|PDB:3UKM" SQ SEQUENCE 336 AA; 38143 MW; 2A41D9501323215D CRC64; MLQSLAGSSC VRLVERHRSA WCFGFLVLGY LLYLVFGAVV FSSVELPYED LLRQELRKLK RRFLEEHECL SEQQLEQFLG RVLEASNYGV SVLSNASGNW NWDFTSALFF ASTVLSTTGY GHTVPLSDGG KAFCIIYSVI GIPFTLLFLT AVVQRITVHV TRRPVLYFHI RWGFSKQVVA IVHAVLLGFV TVSCFFFIPA AVFSVLEDDW NFLESFYFCF ISLSTIGLGD YVPGEGYNQK FRELYKIGIT CYLLLGLIAM LVVLETFCEL HELKKFRKMF YVKKDKDEDQ VHIIEHDQLS FSSITDQAAG MKEDQKQNEP FVATQSSACV DGPANH //