K2P3.1
Target not currently curated in GtoImmuPdb
Target id: 515
Nomenclature: K2P3.1
Abbreviated Name: TASK1
Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Associated Proteins
- Functional Characteristics
- Ion Selectivity and Conductance
- Activators
- Channel Blockers
- Tissue Distribution
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- General Comments
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 4 | 2 | 394 | 2p23.3 | KCNK3 | potassium two pore domain channel subfamily K member 3 | 16 |
| Mouse | 4 | 2 | 409 | 5 16.68 cM | Kcnk3 | potassium channel, subfamily K, member 3 | 16 |
| Rat | 4 | 2 | 411 | 6q14 | Kcnk3 | potassium two pore domain channel subfamily K member 3 | 12 |
| Previous and Unofficial Names |
| TASK-1 | OAT-1 | TWIK-related acid-sensitive K+ channel | two pore potassium channel KT3.1 | potassium channel, two pore domain subfamily K, member 3 | potassium channel |
| Database Links |
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| Alphafold | O14649 (Hs), O35111 (Mm), O54912 (Rn) |
| ChEMBL Target | CHEMBL2321613 (Hs), CHEMBL4294 (Rn) |
| DrugBank Target | O14649 (Hs) |
| Ensembl Gene | ENSG00000171303 (Hs), ENSMUSG00000049265 (Mm), ENSRNOG00000009790 (Rn) |
| Entrez Gene | 3777 (Hs), 16527 (Mm), 29553 (Rn) |
| Human Protein Atlas | ENSG00000171303 (Hs) |
| KEGG Gene | hsa:3777 (Hs), mmu:16527 (Mm), rno:29553 (Rn) |
| OMIM | 603220 (Hs) |
| Orphanet | ORPHA360868 (Hs) |
| Pharos | O14649 (Hs) |
| RefSeq Nucleotide | NM_002246 (Hs), NM_010608 (Mm), NM_033376 (Rn) |
| RefSeq Protein | NP_002237 (Hs), NP_034738 (Mm), NP_203694 (Rn) |
| UniProtKB | O14649 (Hs), O35111 (Mm), O54912 (Rn) |
| Wikipedia | KCNK3 (Hs) |
| Associated Proteins |
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| Associated Protein Comments | ||||||||||||||||||||||||||||
| Heteromultimers shown to form in vivo: K2P3 has been shown to form heterodimers with K2P9 in rat cerebellar granule neurons [6], in rat carotid body glomus cells [7] and in motoneurons [1] and with K2P1 in rat cerebellar granule neurons [21]. Protein-protein interactions: K2P3 has been found to associate with syntaxin-8 [22]; 14-3-3 [18] and the coatomer coat protein 1 (COP1) [18] and Vpu1 [5]. Binding of 14-3-3 and COP1 control forward trafficking of K2P3 from the ER [18]. Forward trafficking is modulated by the binding of p11 to K2P3 in a 14-3-3 dependent manner [19]. The electrical activity of K2P3-K2P1 heterodimers at the plasma membrane is controlled by SUMOylation of the K2P1 subunit [21]. |
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| Functional Characteristics |
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| Background current | |
| Ion Selectivity and Conductance Comments |
| K2P3.1 or TASK-1 channels generate instantaneous, open-rectifier K+ currents (showing the Goldman-Hodgkin-Katz (GHK) rectifier behaviour) [12]. |
Download all structure-activity data for this target as a CSV file 
| Activators | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific activator tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Activator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Volatile anesthetics are known activators of the K2P3.1 channels [2,8,24]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific channel blocker tables | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Channel Blocker Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proton block and voltage gating are potassium-dependent in K2P3.1. The channels are modulated by external pH [4,13-14]. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| Other reports have suggested expression in pancreas, prostate, uterus and placenta. | ||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| General Comments |
| ‘Activation’ and ‘deactivation’ with voltage steps appears to be instantaneous but there is also a small, time-dependent change in Po. Current is half-blocked at pH 7.3 at physiological external conditions; increasing external potassium decreases proton blockade. Pharmacology studies of the rat variant reveal blockade also by zinc, TEA and quinidine [10,23]. K2P3 like currents are reported in cerebellar granular neurons and motor-neurons [10,17]. Interaction with 14-3-3 protein is essential for forward trafficking. K2P3 can form heterodimers with K2P9.1 in heterologous expression systems consistent with electrophysiological studies that suggest heterodimerzation. K2P3 is also suggested to be a target for transmitter modulation of neuronal excitability [10,17]. |
References
1. Berg AP, Talley EM, Manger JP, Bayliss DA. (2004) Motoneurons express heteromeric TWIK-related acid-sensitive K+ (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits. J Neurosci, 24 (30): 6693-702. [PMID:15282272]
2. Buckler KJ, Williams BA, Honore E. (2000) An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells. J Physiol (Lond.), 525 Pt 1: 135-42. [PMID:10811732]
3. Czirják G, Fischer T, Spät A, Lesage F, Enyedi P. (2000) TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II. Mol Endocrinol, 14 (6): 863-74. [PMID:10847588]
4. Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M. (1997) TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J, 16 (17): 5464-71. [PMID:9312005]
5. Hsu K, Seharaseyon J, Dong P, Bour S, Marbán E. (2004) Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Mol Cell, 14 (2): 259-67. [PMID:15099524]
6. Kang D, Han J, Talley EM, Bayliss DA, Kim D. (2004) Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells. J Physiol (Lond.), 554 (Pt 1): 64-77. [PMID:14678492]
7. Kim D, Cavanaugh EJ, Kim I, Carroll JL. (2009) Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells. J Physiol (Lond.), 587 (Pt 12): 2963-75. [PMID:19403596]
8. Kim D, Fujita A, Horio Y, Kurachi Y. (1998) Cloning and functional expression of a novel cardiac two-pore background K+ channel (cTBAK-1). Circ Res, 82 (4): 513-8. [PMID:9506712]
9. Kim Y, Bang H, Kim D. (1999) TBAK-1 and TASK-1, two-pore K(+) channel subunits: kinetic properties and expression in rat heart. Am J Physiol, 277 (5): H1669-78. [PMID:10564119]
10. Kindler CH, Yost CS, Gray AT. (1999) Local anesthetic inhibition of baseline potassium channels with two pore domains in tandem. Anesthesiology, 90 (4): 1092-102. [PMID:10201682]
11. Lazarenko RM, Willcox SC, Shu S, Berg AP, Jevtovic-Todorovic V, Talley EM, Chen X, Bayliss DA. (2010) Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics. J Neurosci, 30 (22): 7691-704. [PMID:20519544]
12. Leonoudakis D, Gray AT, Winegar BD, Kindler CH, Harada M, Taylor DM, Chavez RA, Forsayeth JR, Yost CS. (1998) An open rectifier potassium channel with two pore domains in tandem cloned from rat cerebellum. J Neurosci, 18 (3): 868-77. [PMID:9437008]
13. Lopes CM, Gallagher PG, Buck ME, Butler MH, Goldstein SA. (2000) Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. J Biol Chem, 275 (22): 16969-78. [PMID:10748056]
14. Lopes CM, Zilberberg N, Goldstein SA. (2001) Block of Kcnk3 by protons. Evidence that 2-P-domain potassium channel subunits function as homodimers. J Biol Chem, 276 (27): 24449-52. [PMID:11358956]
15. Maingret F, Patel AJ, Lazdunski M, Honoré E. (2001) The endocannabinoid anandamide is a direct and selective blocker of the background K(+) channel TASK-1. EMBO J, 20 (1-2): 47-54. [PMID:11226154]
16. Manjunath NA, Bray-Ward P, Goldstein SA, Gallagher PG. (1999) Assignment of the 2P domain, acid-sensitive potassium channel OAT1 gene KCNK3 to human chromosome bands 2p24.1-->p23.3 and murine 5B by in situ hybridization. Cytogenet Cell Genet, 86 (3-4): 242-3. [PMID:10575216]
17. Millar JA, Barratt L, Southan AP, Page KM, Fyffe RE, Robertson B, Mathie A. (2000) A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons. Proc Natl Acad Sci USA, 97 (7): 3614-8. [PMID:10725353]
18. O'Kelly I, Butler MH, Zilberberg N, Goldstein SA. (2002) Forward transport. 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals. Cell, 111 (4): 577-88. [PMID:12437930]
19. O'Kelly I, Goldstein SA. (2008) Forward Transport of K2p3.1: mediation by 14-3-3 and COPI, modulation by p11. Traffic, 9 (1): 72-8. [PMID:17908283]
20. Patel AJ, Honoré E, Maingret F, Lesage F, Fink M, Duprat F, Lazdunski M. (1998) A mammalian two pore domain mechano-gated S-like K+ channel. EMBO J, 17 (15): 4283-90. [PMID:9687497]
21. 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]
22. Renigunta V, Fischer T, Zuzarte M, Kling S, Zou X, Siebert K, Limberg MM, Rinné S, Decher N, Schlichthörl G et al.. (2014) Cooperative endocytosis of the endosomal SNARE protein syntaxin-8 and the potassium channel TASK-1. Mol Biol Cell, 25 (12): 1877-91. [PMID:24743596]
23. Talley EM, Lei Q, Sirois JE, Bayliss DA. (2000) TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons. Neuron, 25 (2): 399-410. [PMID:10719894]
24. Washburn CP, Sirois JE, Talley EM, Guyenet PG, Bayliss DA. (2002) Serotonergic raphe neurons express TASK channel transcripts and a TASK-like pH- and halothane-sensitive K+ conductance. J Neurosci, 22 (4): 1256-65. [PMID:11850453]
25. Wiedmann F, Kiper AK, Bedoya M, Ratte A, Rinné S, Kraft M, Waibel M, Anad P, Wenzel W, González W et al.. (2019) Identification of the A293 (AVE1231) Binding Site in the Cardiac Two-Pore-Domain Potassium Channel TASK-1: a Common Low Affinity Antiarrhythmic Drug Binding Site. Cell Physiol Biochem, 52 (5): 1223-1235. [PMID:31001961]
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