K2P1.1 channels

Channel name K2P1.1
Description Two-pore domain potassium channel subunit1
Other names KCNK1, TWIK-1, hOHO
Molecular information Human: 336aa, NM_002245, chr. 1q42-43, KCNK1,2,3 GeneID: 3775, PMID: 86058691
Rat: 336aa, AF022819
Mouse: 336aa, NM_008430, chr. 8, kcnk14
Associated subunits Small ubiquitin-related modifier protein (SUMO-1) is covalently attached at lysine 2746; exchange factor (EFA6) for small G protein ADP-ribosylation factor 6 (ARF6) (see “Comments”)7
Functional assays Electrophysiological
Current Open rectifier
Conductance 32pS
Ion selectivity Not established
Activation See “Comments”
Inactivation See “Comments”
Activators Not established
Gating inhibitors None
Blockers External pH (6.7)6
Radioligands None
Channel distribution Brain, heart, lung, kidney, liver, placenta4,5
Physiological functions Not established
Mutations and pathophysiology Not established
Pharmacological significance Not established
Comments Covalent attachment of SUMO to lysine 274 silences K2P1; mutation of lysine 274 or desumoylation of K2P1 by a SUMO-specific protease (SENP) reveals an open rectifier; like K2P3 and K2P9, K2P1 is blocked by extracellular acidification due to titration of a histidine residue in the first pore loop; EFA6 interacts with the C-terminal part of K2P1—this interaction may be important for channel internalization and recycling7
  • aa, amino acid; chr., chromosome; SUMO, small ubiquitin-related modifier protein.

  • 1. Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, and Barhanin J (1996) TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO J 15:1004-1011

  • 2. Orias M, Velazquez H, Tung F, Lee G, and Desir GV (1997) Cloning and localization of a double-pore K channel, KCNK1: exclusive expression in distal nephron segments. Am J Physiol 273: F663-F666

  • 3. Lesage F, Mattei MG, Fink M, Barhanin J, and Lazdunski M (1996) Assignment of the human weak inward rectifier K+ channel TWIK-1 gene to chromosome 1q42-q43. Genomics 34:153-155

  • 4. Lesage F, Lauritzen I, Duprat F, Reyes R, Fink M, Heurteaux C, and Lazdunski M (1997) The structure, function and distribution of the mouse TWIK-1 K+ channel. FEBS Lett 402:28-32

  • 5. Goldstein SAN, Wang KW, Ilan N, and Pausch M (1998) Sequence and function of the two P domain potassium channels: implications of an emerging superfamily. J Mol Med 76:13-20

  • 6. Rajan S, Plant LD, Rabin ML, Butler MH, and Goldstein SAN (2005) Sumoylation silences the plasma membrane leak K+ channel K2P1. Cell 121:37-47

  • 7. Decressac S, Franco M, Bendahhou S, Warth R, Knauer S, Barhanin J, Lazdunski M, and Lesage F (2004) ARF6-dependent interaction of the TWIK1 K + channel with EFA6, GDP/GTP exchange factor for ARF6. EMBO Rep 5:1171-1175