KCNK4
| Potassium channel, subfamily K, member 4 | |||||||||||||
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 Crystallographic structure of TRAAK. The gray boxes indicate approximate location of the lipid bilayer.[1] | |||||||||||||
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| Identifiers | |||||||||||||
| Symbols | KCNK4; K2p4.1; TRAAK; TRAAK1 | ||||||||||||
| External IDs | OMIM: 605720 MGI: 1298234 HomoloGene: 7391 IUPHAR: K2P4.1 GeneCards: KCNK4 Gene | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 50801 | 16528 | |||||||||||
| Ensembl | ENSG00000182450 | ENSMUSG00000024957 | |||||||||||
| UniProt | Q9NYG8 | O88454 | |||||||||||
| RefSeq (mRNA) | NM_016611 | NM_008431 | |||||||||||
| RefSeq (protein) | NP_201567 | NP_032457 | |||||||||||
| Location (UCSC) | Chr 11: 64.06 – 64.07 Mb | Chr 19: 6.93 – 6.93 Mb | |||||||||||
| PubMed search | |||||||||||||
Potassium channel subfamily K member 4 is a protein that in humans is encoded by the KCNK4 gene.[2][3][4]
Function
Potassium channels play a role in many cellular processes including maintenance of the action potential, muscle contraction, hormone secretion, osmotic regulation, and ion flow. This gene encodes the K2P4.1 protein, one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. K2P4.1 homodimerizes and functions as an outwardly rectifying channel. It is expressed primarily in neural tissues and is stimulated by membrane stretch and polyunsaturated fatty acids.[4]
KCNK4 protein channels are also called TRAAK channels. TRAAK channels are found in mammalian neurons and are part of a protein family of weakly inward rectifying potassium channels. This subfamily of potassium channels is mechanically gated. The C-terminal of TRAAK has a charged cluster that is important in maintaining the mechanosensitive properties of the channel.[5]
TRAAK is only expressed in neuronal tissue, and can be found in the brain, spinal cord, and retina, which suggests that it has a function beyond mechanotransduction in terms of neuronal excitability.[6] The highest levels of TRAAK expression are in the olfactory system, cerebral cortex, hippocampal formation, habenula, basal ganglia, and cerebellum.[6] TRAAK channels are mechanically activated when there is a convex curvature in the membrane that alters the channel’s activity. TRAAK channels are thought to have a role in axonal pathfinding, growth cone motility, and neurite elongation, as well as possibly having a role in touch or pain detection.[7][8]
See also
References
- ↑ PDB 3UM7; Brohawn SG, del Mármol J, MacKinnon R (27 January 2012). "Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel". Science 335 (6067): 436–41. doi:10.1126/science.1213808. PMID 22282805.
- ↑ Lesage F, Maingret F, Lazdunski M (May 2000). "Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel". FEBS Lett 471 (2–3): 137–40. doi:10.1016/S0014-5793(00)01388-0. PMID 10767409.
- ↑ Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S (Dec 2005). "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacol Rev 57 (4): 527–40. doi:10.1124/pr.57.4.12. PMID 16382106.
- ↑ 4.0 4.1 "Entrez Gene: KCNK4 potassium channel, subfamily K, member 4".
- ↑ Patel AJ, Honoré E, Lesage F, Fink M, Romey G, Lazdunski M (1999). "Inhalational anesthetics activate two-pore-domain background K+ channels". Nature Neuroscience 2 (5): 422–426. doi:10.1038/8084. PMID 10321245.
- ↑ 6.0 6.1 Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M (1998). "A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids". The EMBO Journal 17 (12): 3297–3308. doi:10.1093/emboj/17.12.3297. PMC 1170668. PMID 9628867.
- ↑ Vandorpe DH, Morris CE (1992). "Stretch activation of the Aplysia S-channel". The Journal of membrane biology 127 (3): 205–214. PMID 1495087.
- ↑ Maingret F, Fosset M, Lesage F, Lazdunski M, Honoré E (1999). "TRAAK is a mammalian neuronal mechano-gated K+ channel". The Journal of Biological Chemistry 274 (3): 1381–1387. PMID 9880510.
Further reading
- Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N (2001). "Potassium leak channels and the KCNK family of two-P-domain subunits". Nat. Rev. Neurosci. 2 (3): 175–84. doi:10.1038/35058574. PMID 11256078.
- Chapman CG, Meadows HJ, Godden RJ et al. (2001). "Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel". Brain Res. Mol. Brain Res. 82 (1–2): 74–83. doi:10.1016/S0169-328X(00)00183-2. PMID 11042359.
- Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- Meadows HJ, Chapman CG, Duckworth DM et al. (2001). "The neuroprotective agent sipatrigine (BW619C89) potently inhibits the human tandem pore-domain K(+) channels TREK-1 and TRAAK". Brain Res. 892 (1): 94–101. doi:10.1016/S0006-8993(00)03239-X. PMID 11172753.
- Wiemann S, Weil B, Wellenreuther R et al. (2001). "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
- Simpson JC, Wellenreuther R, Poustka A et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
- Ozaita A, Vega-Saenz de Miera E (2003). "Cloning of two transcripts, HKT4.1a and HKT4.1b, from the human two-pore K+ channel gene KCNK4. Chromosomal localization, tissue distribution and functional expression". Brain Res. Mol. Brain Res. 102 (1–2): 18–27. doi:10.1016/S0169-328X(02)00157-2. PMID 12191490.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Hillman RT, Green RE, Brenner SE (2005). "An unappreciated role for RNA surveillance". Genome Biol. 5 (2): R8. doi:10.1186/gb-2004-5-2-r8. PMC 395752. PMID 14759258.
- Harinath S, Sikdar SK (2004). "Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels". Neuropharmacology 46 (5): 750–60. doi:10.1016/j.neuropharm.2003.11.023. PMID 14996553.
- Wiemann S, Arlt D, Huber W et al. (2004). "From ORFeome to Biology: A Functional Genomics Pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
- Kimura K, Wakamatsu A, Suzuki Y et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Mehrle A, Rosenfelder H, Schupp I et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
External links
- KCNK4 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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