Top ▲
Target not currently curated in GtoImmuPdb
Target id: 527
Nomenclature: K2P18.1
Abbreviated Name: TRESK
Gene and Protein Information  |
|||||||
| Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 4 | 2 | 384 | 10q25.3 | KCNK18 | potassium two pore domain channel subfamily K member 18 | 8 |
| Mouse | 4 | 2 | 394 | 19 D3 | Kcnk18 | potassium channel, subfamily K, member 18 | |
| Rat | 4 | 2 | 405 | 1q55 | Kcnk18 | potassium two pore domain channel subfamily K member 18 | |
| Previous and Unofficial Names |
| TRESK-1/TRESK-2 | TRIK | TWIK related spinal cord K+ channel | tandem-pore K+ (K(2P)) channel | two-pore-domain potassium channel TRESK | potassium channel, two pore domain subfamily K, member 18 | potassium channel |
| Database Links |
|
| Alphafold | Q7Z418 (Hs), Q6VV64 (Mm), Q6Q1P3 (Rn) |
| ChEMBL Target | CHEMBL2331042 (Hs) |
| Ensembl Gene | ENSG00000186795 (Hs), ENSMUSG00000040901 (Mm), ENSRNOG00000032706 (Rn) |
| Entrez Gene | 338567 (Hs), 332396 (Mm), 445371 (Rn) |
| Human Protein Atlas | ENSG00000186795 (Hs) |
| KEGG Gene | hsa:338567 (Hs), mmu:332396 (Mm), rno:445371 (Rn) |
| OMIM | 613655 (Hs) |
| Pharos | Q7Z418 (Hs) |
| RefSeq Nucleotide | NM_181840 (Hs), NM_207261 (Mm), NM_001003820 (Rn) |
| RefSeq Protein | NP_862823 (Hs), NP_997144 (Mm), NP_001003820 (Rn) |
| UniProtKB | Q7Z418 (Hs), Q6VV64 (Mm), Q6Q1P3 (Rn) |
| Wikipedia | KCNK18 (Hs) |
| Associated Proteins |
||||||||||||||||||||||||
|
|
|
||||||||||||||||||||||
| Associated Protein Comments | ||||||||||||||||||||||||
| Protein-protein interactions: Calcineurin binds to the intracellular loop of human K2P18 at two non-catalytic interacting motifs (PQIIIS and LQLP). The binding is necessary for the phosphatase to dephosphorylate and activate the channel [2-3]. 14-3-3 proteins bind to the RSNpSCP mode I motif of the intracellular loop of human K2P18. The binding is phosphorylation dependent and contributes to the inhibition of the channel after phosphorylation [5]. Tubulin binds in vitro to the intracellular loop of TRESK. The significance of this interaction is unknown [6]. | ||||||||||||||||||||||||
| Functional Characteristics |
|
| Background current | |
Download all structure-activity data for this target as a CSV file 
| Activator Comments | ||
| The Two-pore Domain K+ Channel, K2P18.1, is activated by cytoplasmic calcium via calcineurin [4] and some volatile anasthetics. |
| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Channel Blocker Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Free fatty acids and external acidic pH have been demonstrated to act as K2p18.1 pore blockers. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tissue Distribution
|
||||||||
|
| Clinically-Relevant Mutations and Pathophysiology
|
||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||
| General Comments |
| Activation is instantaneous, single channel currents are non-inactivating and time dependent. TRESK2 was cloned from mouse testis and shares 65% homology with human K2P18. As study continues it will become clear if this is the true correlate of the human channel or a distinct gene (K2P19). It is suspected that distinct cDNAs for both TRESK-1 and TRESK-2 are present in human tissues. |
1. Andres-Enguix I, Shang L, Stansfeld PJ, Morahan JM, Sansom MS, Lafrenière RG, Roy B, Griffiths LR, Rouleau GA, Ebers GC et al.. (2012) Functional analysis of missense variants in the TRESK (KCNK18) K channel. Sci Rep, 2: 237. [PMID:22355750]
2. Czirják G, Enyedi P. (2006) Targeting of calcineurin to an NFAT-like docking site is required for the calcium-dependent activation of the background K+ channel, TRESK. J Biol Chem, 281 (21): 14677-82. [PMID:16569637]
3. Czirják G, Enyedi P. (2014) The LQLP calcineurin docking site is a major determinant of the calcium-dependent activation of human TRESK background K+ channel. J Biol Chem, 289 (43): 29506-18. [PMID:25202008]
4. Czirják G, Tóth ZE, Enyedi P. (2004) The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin. J Biol Chem, 279 (18): 18550-8. [PMID:14981085]
5. Czirják G, Vuity D, Enyedi P. (2008) Phosphorylation-dependent binding of 14-3-3 proteins controls TRESK regulation. J Biol Chem, 283 (23): 15672-80. [PMID:18397886]
6. Enyedi P, Veres I, Braun G, Czirják G. (2014) Tubulin binds to the cytoplasmic loop of TRESK background K⁺ channel in vitro. PLoS ONE, 9 (5): e97854. [PMID:24830385]
7. Lafrenière RG, Cader MZ, Poulin JF, Andres-Enguix I, Simoneau M, Gupta N, Boisvert K, Lafrenière F, McLaughlan S, Dubé MP et al.. (2010) A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura. Nat Med, 16 (10): 1157-60. [PMID:20871611]
8. Sano Y, Inamura K, Miyake A, Mochizuki S, Kitada C, Yokoi H, Nozawa K, Okada H, Matsushime H, Furuichi K. (2003) A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord. J Biol Chem, 278 (30): 27406-12. [PMID:12754259]
