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