KCNK13

KCNK13
Identifiers
Aliases	KCNK13 , K2p13.1, THIK-1, THIK1, potassium two pore domain channel subfamily K member 13
External IDs	OMIM: 607367; MGI: 2384976; HomoloGene: 69351; GeneCards: KCNK13; OMA:KCNK13 - orthologs
Gene location (Human) Chr. Chromosome 14 (human) [1] Band 14q32.11 Start 90,061,994 bp [1] End 90,185,853 bp [1]
Gene location (Mouse) Chr. Chromosome 12 (mouse) [2] Band 12|12 E Start 99,930,758 bp [2] End 100,028,941 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right testis left testis monocyte granulocyte appendix human kidney right auricle of heart left lobe of thyroid gland prefrontal cortex right lobe of thyroid gland Top expressed in secondary oocyte stroma of bone marrow primary oocyte zygote embryo left lung lobe superior frontal gyrus deep cerebellar nuclei dentate gyrus of hippocampal formation granule cell primary visual cortex More reference expression data BioGPS n/a
Gene ontology Molecular function potassium channel activity voltage-gated ion channel activity potassium ion leak channel activity Cellular component integral component of membrane plasma membrane membrane integral component of plasma membrane Biological process potassium ion transport regulation of ion transmembrane transport ion transport stabilization of membrane potential potassium ion transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 56659 217826 Ensembl ENSG00000152315 ENSMUSG00000045404 UniProt Q9HB14 Q8R1P5 RefSeq (mRNA) NM_022054 NM_001164426 NM_001164427 NM_146037 RefSeq (protein) NP_071337 NP_001157898 NP_001157899 NP_666149 Location (UCSC) Chr 14: 90.06 – 90.19 Mb Chr 12: 99.93 – 100.03 Mb PubMed search [3] [4]
Wikidata
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Potassium channel, subfamily K, member 13 (KCNK13), also known as K_2P13.1 or THIK-1, is a protein that in humans is encoded by the KCNK13 gene. It is a potassium channel containing two pore-forming P domains. ^{[5] [6]}

Function

Ribbon structure of homodimeric two-pore potassium channel K2P13 (THIK-1).

K_2P13.1 was first discovered in 2000 from a rat cDNA library, along with the closely related protein K_2P12.1 ^[5] The two channels were named tandem pore domain halothane-inhibited K⁺ channel 1 and 2 (THIK-1 and THIK-2) because the anesthetic halothane inhibited the potassium current. THIK-1 was also shown to be activated by arachidonic acid and displayed mild voltage dependence, with moderate outward rectification at low external K⁺ and weak inward rectification with nearly symmetrical K⁺ concentrations. ^{[5] [8]} Later research showed that THIK-1 can be activated by G-protein-coupled receptor pathways ^[9] and by polyanionic lipids such as PIP₂ and oleoyl-CoA. ^[10]

In humans, THIK-1 expression is almost exclusively restricted to microglia, where it functions as the main potassium channel and is responsible for maintaining their resting membrane potential through tonic background potassium conductance. ^[11] THIK-1 activity can regulate microglial ramification, surveillance, NLRP3 inflammasome activation, and subsequent release of pro-inflammatory cytokine interleukin-1β (IL-1β). ^{[12] [13] [14]} It also plays a role in cell shrinkage during apoptosis via caspase-8 cleavage. ^[15]

See also

• Tandem pore domain potassium channel

References

1. GRCh38: Ensembl release 89: ENSG00000152315 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000045404 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Rajan S, Wischmeyer E, Karschin C, Preisig-Müller R, Grzeschik KH, Daut J, et al. (March 2001). "THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels". The Journal of Biological Chemistry. 276 (10): 7302–7311. doi: 10.1074/jbc.M008985200 . PMID   11060316.
6. Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S (December 2005). "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacological Reviews. 57 (4): 527–540. doi:10.1124/pr.57.4.12. PMID   16382106. S2CID   7356601.
7. Rödström KE, Eymsh B, Proks P, Hayre MS, Madry C, Rowland A, et al. (2024-06-27). "CryoEM Structure of the human THIK-1 K2P K+ Channel Reveals a Lower 'Y-gate' Regulated by Lipids and Anaesthetics". bioRxiv   10.1101/2024.06.26.600475 .
8. Aggarwal P, Singh S, Ravichandiran V (2021-08-01). "Two-Pore Domain Potassium Channel in Neurological Disorders" . The Journal of Membrane Biology. 254 (4): 367–380. doi:10.1007/s00232-021-00189-8. ISSN   1432-1424. PMID   34169340.
9. Tateyama M, Kubo Y (2023-04-26). "Regulation of the two-pore domain potassium channel, THIK-1 and THIK-2, by G protein coupled receptors". PLOS ONE. 18 (4) e0284962. Bibcode:2023PLoSO..1884962T. doi: 10.1371/journal.pone.0284962 . ISSN   1932-6203. PMC   10132538 . PMID   37099539.
10. Riel EB, Jurs BC, Cordeiro S, Musinszki M, Schewe M, Baukrowitz T (2022-02-07). "The versatile regulation of K2P channels by polyanionic lipids of the phosphoinositide and fatty acid metabolism". The Journal of General Physiology. 154 (2) e202112989. doi:10.1085/jgp.202112989. ISSN   0022-1295. PMC   8693234 . PMID   34928298.
11. Rifat A, Ossola B, Burli RW, Dawson LA, Brice NL, Rowland A, et al. (2024-02-26). "Differential contribution of THIK-1 K+ channels and P2X7 receptors to ATP-mediated neuroinflammation by human microglia". Journal of Neuroinflammation. 21 (1) 58. doi: 10.1186/s12974-024-03042-6 . ISSN   1742-2094. PMC   10895799 . PMID   38409076.
12. Madry C, Kyrargyri V, Arancibia-Carcamo IL, Jolivet R, Kohsaka S, Bryan RM, et al. (January 2018). "Microglial Ramification, Surveillance, and Interleukin-1β Release Are Regulated by the Two-Pore Domain K+ Channel THIK-1". Neuron. 97 (2): 299–312.e6. doi:10.1016/j.neuron.2017.12.002. PMC   5783715 . PMID   29290552.
13. Xu Z, Chen ZM, Wu X, Zhang L, Cao Y, Zhou P (2020-12-07). "Distinct Molecular Mechanisms Underlying Potassium Efflux for NLRP3 Inflammasome Activation". Frontiers in Immunology. 11 609441. doi: 10.3389/fimmu.2020.609441 . ISSN   1664-3224. PMC   7793832 . PMID   33424864.
14. Drinkall S, Lawrence CB, Ossola B, Russell S, Bender C, Brice NB, et al. (2022). "The two pore potassium channel THIK-1 regulates NLRP3 inflammasome activation". Glia. 70 (7): 1301–1316. doi:10.1002/glia.24174. ISSN   1098-1136. PMC   9314991 . PMID   35353387.
15. Sakamaki K, Ishii TM, Sakata T, Takemoto K, Takagi C, Takeuchi A, et al. (2016-11-01). "Dysregulation of a potassium channel, THIK-1, targeted by caspase-8 accelerates cell shrinkage" . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1863 (11): 2766–2783. doi:10.1016/j.bbamcr.2016.08.010. ISSN   0167-4889. PMID   27566292.

Further reading

• Fearon IM, Campanucci VA, Brown ST, Hudasek K, O'Kelly IM, Nurse CA (2006). "Acute hypoxic regulation of recombinant THIK-1 stably expressed in HEK293 cells". The Arterial Chemoreceptors. Advances in Experimental Medicine and Biology. Vol. 580. pp. 203–8, discussion 351–9. doi:10.1007/0-387-31311-7_31. ISBN   978-0-387-31310-8. PMID   16683720.
• Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N (Mar 2001). "Potassium leak channels and the KCNK family of two-P-domain subunits". Nature Reviews. Neuroscience. 2 (3): 175–184. doi:10.1038/35058574. PMID   11256078. S2CID   9682396.
• Theilig F, Goranova I, Hirsch JR, Wieske M, Unsal S, Bachmann S, et al. (2008). "Cellular localization of THIK-1 (K(2P)13.1) and THIK-2 (K(2P)12.1) K channels in the mammalian kidney". Cellular Physiology and Biochemistry. 21 (1–3): 63–74. doi: 10.1159/000113748 . PMID   18209473.
• Gierten J, Ficker E, Bloehs R, Schlomer K, Kathofer S, Scholz E, et al. (Aug 2008). "Regulation of two-pore-domain (K2P) potassium leak channels by the tyrosine kinase inhibitor genistein". British Journal of Pharmacology. 154 (8): 1680–1690. doi:10.1038/bjp.2008.213. PMC   2518462 . PMID   18516069.

External links

• KCNK13+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)