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 (TC
CC 1.A.1.8) family. {ECO:0000305}.
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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 Genevisible; O00180; HS.
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.
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
//
