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Target not currently curated in GtoImmuPdb
Target id: 513
Nomenclature: K2P1.1
Abbreviated Name: TWIK1
Gene and Protein Information  |
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| 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 |
| TWIK-1 | hOHO | DPK | potassium channel, subfamily K, member 1 | potassium channel, two pore domain subfamily K, member 1 | potassium channel |
| Database Links |
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| Alphafold | O00180 (Hs), O08581 (Mm), Q9Z2T2 (Rn) |
| Ensembl Gene | ENSG00000135750 (Hs), ENSMUSG00000033998 (Mm), ENSRNOG00000019937 (Rn) |
| Entrez Gene | 3775 (Hs), 16525 (Mm), 59324 (Rn) |
| Human Protein Atlas | ENSG00000135750 (Hs) |
| KEGG Gene | hsa:3775 (Hs), mmu:16525 (Mm), rno:59324 (Rn) |
| OMIM | 601745 (Hs) |
| Pharos | O00180 (Hs) |
| RefSeq Nucleotide | NM_002245 (Hs), NM_008430 (Mm), NM_021688 (Rn) |
| RefSeq Protein | NP_002236 (Hs), NP_032456 (Mm), NP_067720 (Rn) |
| UniProtKB | O00180 (Hs), O08581 (Mm), Q9Z2T2 (Rn) |
| Wikipedia | KCNK1 (Hs) |
| Associated Proteins |
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| 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]. |
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| Functional Characteristics |
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| Background current | |
| Ion Selectivity and Conductance |
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| Ion Selectivity and Conductance Comments | ||||||
| K2P1 is a K+-selective, pH-sensitive, openly rectifying channel regulated by reversible peptide linkage [10]. |
| Tissue Distribution
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| Functional Assays
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| 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]. |
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]
