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Target id: 513

Nomenclature: K2P1.1

Abbreviated Name: TWIK1

Family: Two-pore domain potassium channels (K2P)

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 2 336 1q42.2 KCNK1 potassium two pore domain channel subfamily K member 1 4,6-7
Mouse 4 2 336 8 E2 Kcnk1 potassium channel, subfamily K, member 1 5
Rat 4 2 336 19q12 Kcnk1 potassium two pore domain channel subfamily K member 1
Previous and Unofficial Names Click here for help
TWIK-1 | hOHO | DPK | potassium channel, subfamily K, member 1 | potassium channel, two pore domain subfamily K, member 1 | potassium channel
Database Links Click here for help
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
K2P3.1 9
K2P2.1 3
K2P9.1 9
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Not determined
Associated Protein Comments
Heteromultimers shown to form in vivo: K2P1 has been shown to form channels with K2P3 and K2P9 subunits in primary cultures of rat cerebellar granule neurons [9] and binds with K2P2 in cortical astrocytes [3].

Protein-protein interactions: K2P1 channels are modified by the small ubiquitin like modifier protein, SUMO at C-terminal lysine K274. SUMOylation of K2P1 has been demonstrated following heterologous expression of the channel in Xenopus oocytes, COS-7 and CHO cells [8,10]. SUMOylation of native K2P1 homodimeric and K2P1 subunit containing heterodimeric channels has been demonstrated in cerebellar granule neurons [9]. In MDCK cells, K2P1 associates with EFA6, an exchange factor for the small G protein ADP-ribosylation factor 6 (ARF6), an interaction that is important for channel endocytosis [1].
Functional Characteristics Click here for help
Background current
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  K+ [- pS]
References:  10
Species:  Human
Single channel conductance (pS):  32
References:  10
Species:  Human
Single channel current rectification:  Outward
References:  10
Ion Selectivity and Conductance Comments
K2P1 is a K+-selective, pH-sensitive, openly rectifying channel regulated by reversible peptide linkage [10].
Tissue Distribution Click here for help
Brain, heart, lung, kidney, placenta.
Species:  Human
Technique:  In situ hybridisation
References:  2,5
Renal proximal tubules
Species:  Mouse
Technique:  Immunocytochemistry
References:  1
Functional Assays Click here for help
Electrophysiology in experimental cells.
Species:  Human
Tissue:  Cloned gene assessed in Xenopus oocytes and COS-7 cells.
Response measured:  Current levels.
References:  10
General 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 [10]. This interaction may be important for channel internalization and recycling [1].


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1. Decressac S, Franco M, Bendahhou S, Warth R, Knauer S, Barhanin J, Lazdunski M, Lesage F. (2004) ARF6-dependent interaction of the TWIK1 K+ channel with EFA6, a GDP/GTP exchange factor for ARF6. EMBO Rep, 5 (12): 1171-5. [PMID:15540117]

2. Goldstein SA, Wang KW, Ilan N, Pausch MH. (1998) Sequence and function of the two P domain potassium channels: implications of an emerging superfamily. J Mol Med, 76 (1): 13-20. [PMID:9462864]

3. Hwang EM, Kim E, Yarishkin O, Woo DH, Han KS, Park N, Bae Y, Woo J, Kim D, Park M et al.. (2014) A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. Nat Commun, 5: 3227. [PMID:24496152]

4. Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J. (1996) TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO J, 15 (5): 1004-11. [PMID:8605869]

5. Lesage F, Lauritzen I, Duprat F, Reyes R, Fink M, Heurteaux C, Lazdunski M. (1997) The structure, function and distribution of the mouse TWIK-1 K+ channel. FEBS Lett, 402 (1): 28-32. [PMID:9013852]

6. Lesage F, Mattéi M, Fink M, Barhanin J, Lazdunski M. (1996) Assignment of the human weak inward rectifier K+ channel TWIK-1 gene to chromosome 1q42-q43. Genomics, 34 (1): 153-5. [PMID:8661042]

7. Orias M, Velázquez H, Tung F, Lee G, Desir GV. (1997) Cloning and localization of a double-pore K channel, KCNK1: exclusive expression in distal nephron segments. Am J Physiol, 273 (4): F663-6. [PMID:9362344]

8. Plant LD, Dementieva IS, Kollewe A, Olikara S, Marks JD, Goldstein SA. (2010) One SUMO is sufficient to silence the dimeric potassium channel K2P1. Proc Natl Acad Sci USA, 107 (23): 10743-8. [PMID:20498050]

9. Plant LD, Zuniga L, Araki D, Marks JD, Goldstein SA. (2012) SUMOylation silences heterodimeric TASK potassium channels containing K2P1 subunits in cerebellar granule neurons. Sci Signal, 5 (251): ra84. [PMID:23169818]

10. Rajan S, Plant LD, Rabin ML, Butler MH, Goldstein SA. (2005) Sumoylation silences the plasma membrane leak K+ channel K2P1. Cell, 121 (1): 37-47. [PMID:15820677]


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