Potassium channel subfamily K member 1

Details

Name
Potassium channel subfamily K member 1
Synonyms
  • HOHO1
  • Inward rectifying potassium channel protein TWIK-1
  • KCNO1
  • Potassium channel K2P1
  • Potassium channel KCNO1
  • TWIK1
Gene Name
KCNK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009972|Potassium channel subfamily K member 1
MLQSLAGSSCVRLVERHRSAWCFGFLVLGYLLYLVFGAVVFSSVELPYEDLLRQELRKLK
RRFLEEHECLSEQQLEQFLGRVLEASNYGVSVLSNASGNWNWDFTSALFFASTVLSTTGY
GHTVPLSDGGKAFCIIYSVIGIPFTLLFLTAVVQRITVHVTRRPVLYFHIRWGFSKQVVA
IVHAVLLGFVTVSCFFFIPAAVFSVLEDDWNFLESFYFCFISLSTIGLGDYVPGEGYNQK
FRELYKIGITCYLLLGLIAMLVVLETFCELHELKKFRKMFYVKKDKDEDQVHIIEHDQLS
FSSITDQAAGMKEDQKQNEPFVATQSSACVDGPANH
Number of residues
336
Molecular Weight
38142.775
Theoretical pI
6.34
GO Classification
Functions
inward rectifier potassium channel activity / potassium channel activity / potassium ion leak channel activity / sodium channel activity
Processes
potassium ion transmembrane transport / potassium ion transport / regulation of resting membrane potential / sodium ion transmembrane transport / stabilization of membrane potential / synaptic transmission
Components
apical plasma membrane / cell junction / cytoplasmic membrane-bounded vesicle / dendrite / integral component of membrane / integral component of plasma membrane / inward rectifier potassium channel complex / perikaryon / plasma membrane / potassium channel complex / recycling endosome / synapse / voltage-gated potassium channel complex
General Function
Sodium channel activity
Specific Function
Ion channel that contributes to passive transmembrane potassium transport and to the regulation of the resting membrane potential in brain astrocytes, but also in kidney and in other tissues (PubMed:15820677, PubMed:21653227). Forms dimeric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel is selective for K(+) ions at physiological potassium concentrations and at neutral pH, but becomes permeable to Na(+) at subphysiological K(+) levels and upon acidification of the extracellular medium (PubMed:21653227, PubMed:22431633). The homodimer has very low potassium channel activity, when expressed in heterologous systems, and can function as weakly inward rectifying potassium channel (PubMed:8605869, PubMed:8978667, PubMed:15820677, PubMed:21653227, PubMed:22431633, PubMed:23169818, PubMed:25001086). Channel activity is modulated by activation of serotonin receptors (By similarity). Heterodimeric channels containing KCNK1 and KCNK2 have much higher activity, and may represent the predominant form in astrocytes (By similarity). Heterodimeric channels containing KCNK1 and KCNK3 or KCNK9 have much higher activity (PubMed:23169818). Heterodimeric channels formed by KCNK1 and KCNK9 may contribute to halothane-sensitive currents (PubMed:23169818). Mediates outward rectifying potassium currents in dentate gyrus granule cells and contributes to the regulation of their resting membrane potential (By similarity). Contributes to the regulation of action potential firing in dentate gyrus granule cells and down-regulates their intrinsic excitability (By similarity). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (By similarity). Required for normal ion and water transport in the kidney (By similarity). Contributes to the regulation of the resting membrane potential of pancreatic beta cells (By similarity). The low channel activity of homodimeric KCNK1 may be due to sumoylation (PubMed:15820677, PubMed:20498050, PubMed:23169818). The low channel activity may be due to rapid internalization from the cell membrane and retention in recycling endosomes (PubMed:19959478).
Pfam Domain Function
Transmembrane Regions
21-41 133-156 182-202 244-267
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0009973|Potassium channel subfamily K member 1 (KCNK1)
ATGCTGCAGTCCCTGGCCGGCAGCTCGTGCGTGCGCCTGGTGGAGCGGCACCGCTCGGCC
TGGTGCTTCGGCTTCCTGGTGCTGGGCTACTTGCTCTACCTGGTCTTCGGCGCAGTGGTC
TTCTCCTCGGTGGAGCTGCCCTATGAGGACCTGCTGCGCCAGGAGCTGCGCAAGCTGAAG
CGACGCTTCTTGGAGGAGCACGAGTGCCTGTCTGAGCAGCAGCTGGAGCAGTTCCTGGGC
CGGGTGCTGGAGGCCAGCAACTACGGCGTGTCGGTGCTCAGCAACGCCTCGGGCAACTGG
AACTGGGACTTCACCTCCGCGCTCTTCTTCGCCAGCACCGTGCTCTCCACCACAGGTTAT
GGCCACACCGTGCCCTTGTCAGATGGAGGTAAGGCCTTCTGCATCATCTACTCCGTCATT
GGCATTCCCTTCACCCTCCTGTTCCTGACGGCTGTGGTCCAGCGCATCACCGTGCACGTC
ACCCGCAGGCCGGTCCTCTACTTCCACATCCGCTGGGGCTTCTCCAAGCAGGTGGTGGCC
ATCGTCCATGCCGTGCTCCTTGGGTTTGTCACTGTGTCCTGCTTCTTCTTCATCCCGGCC
GCTGTCTTCTCAGTCCTGGAGGATGACTGGAACTTCCTGGAATCCTTTTATTTTTGTTTT
ATTTCCCTGAGCACCATTGGCCTGGGGGATTATGTGCCTGGGGAAGGCTACAATCAAAAA
TTCAGAGAGCTCTATAAGATTGGGATCACGTGTTACCTGCTACTTGGCCTTATTGCCATG
TTGGTAGTTCTGGAAACCTTCTGTGAACTCCATGAGCTGAAAAAATTCAGAAAAATGTTC
TATGTGAAGAAGGACAAGGACGAGGATCAGGTGCACATCATAGAGCATGACCAACTGTCC
TTCTCCTCGATCACAGACCAGGCAGCTGGCATGAAAGAGGACCAGAAGCAAAATGAGCCT
TTTGTGGCCACCCAGTCATCTGCCTGCGTGGATGGCCCTGCAAACCATTGA
Chromosome Location
1
Locus
1q42-q43
External Identifiers
ResourceLink
UniProtKB IDO00180
UniProtKB Entry NameKCNK1_HUMAN
GenBank Protein ID1086491
GenBank Gene IDU33632
GenAtlas IDKCNK1
HGNC IDHGNC:6272
General References
  1. Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J: TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO J. 1996 Mar 1;15(5):1004-11. [PubMed:8605869]
  2. Goldstein SA, Wang KW, Ilan N, Pausch MH: Sequence and function of the two P domain potassium channels: implications of an emerging superfamily. J Mol Med (Berl). 1998 Jan;76(1):13-20. [PubMed:9462864]
  3. Orias M, Velazquez H, Tung F, Lee G, Desir GV: Cloning and localization of a double-pore K channel, KCNK1: exclusive expression in distal nephron segments. Am J Physiol. 1997 Oct;273(4 Pt 2):F663-6. [PubMed:9362344]
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  6. Lesage F, Reyes R, Fink M, Duprat F, Guillemare E, Lazdunski M: Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge. EMBO J. 1996 Dec 2;15(23):6400-7. [PubMed:8978667]
  7. Medhurst AD, Rennie G, Chapman CG, Meadows H, Duckworth MD, Kelsell RE, Gloger II, Pangalos MN: Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery. Brain Res Mol Brain Res. 2001 Jan 31;86(1-2):101-14. [PubMed:11165377]
  8. Rajan S, Plant LD, Rabin ML, Butler MH, Goldstein SA: Sumoylation silences the plasma membrane leak K+ channel K2P1. Cell. 2005 Apr 8;121(1):37-47. [PubMed:15820677]
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  11. Feliciangeli S, Tardy MP, Sandoz G, Chatelain FC, Warth R, Barhanin J, Bendahhou S, Lesage F: Potassium channel silencing by constitutive endocytosis and intracellular sequestration. J Biol Chem. 2010 Feb 12;285(7):4798-805. doi: 10.1074/jbc.M109.078535. Epub 2009 Dec 3. [PubMed:19959478]
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  13. Ma L, Zhang X, Chen H: TWIK-1 two-pore domain potassium channels change ion selectivity and conduct inward leak sodium currents in hypokalemia. Sci Signal. 2011 Jun 7;4(176):ra37. doi: 10.1126/scisignal.2001726. [PubMed:21653227]
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  16. Chatelain FC, Bichet D, Douguet D, Feliciangeli S, Bendahhou S, Reichold M, Warth R, Barhanin J, Lesage F: TWIK1, a unique background channel with variable ion selectivity. Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5499-504. doi: 10.1073/pnas.1201132109. Epub 2012 Mar 19. [PubMed:22431633]
  17. Plant LD, Zuniga L, Araki D, Marks JD, Goldstein SA: SUMOylation silences heterodimeric TASK potassium channels containing K2P1 subunits in cerebellar granule neurons. Sci Signal. 2012 Nov 20;5(251):ra84. doi: 10.1126/scisignal.2003431. [PubMed:23169818]
  18. Feliciangeli S, Chatelain FC, Bichet D, Lesage F: The family of K2P channels: salient structural and functional properties. J Physiol. 2015 Jun 15;593(12):2587-603. doi: 10.1113/jphysiol.2014.287268. Epub 2015 Jan 22. [PubMed:25530075]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00308IbutilideapprovedunknowninhibitorDetails
DB00908Quinidineapproved, investigationalunknowninhibitorDetails
DB01346Quinidine barbiturateapprovedunknowninhibitorDetails