6wcc

Structural highlights

Disease

TM175_HUMAN Disease susceptibility may be associated with variations affecting the gene represented in this entry. TMEM175 defects result in unstable lysosomal pH, leading to decreased lysosomal catalytic activity, decreased glucocerebrosidase activity, impaired autophagosome clearance by the lysosome and decreased mitochondrial respiration (PubMed:28193887).^[1]

Function

TM175_HUMAN Organelle-specific potassium channel specifically responsible for potassium conductance in endosomes and lysosomes. Forms a potassium-permeable leak-like channel, which regulates lumenal pH stability and is required for autophagosome-lysosome fusion. Constitutes the major lysosomal potassium channel.^{[2] [3]}

References

1. ↑ Jinn S, Drolet RE, Cramer PE, Wong AH, Toolan DM, Gretzula CA, Voleti B, Vassileva G, Disa J, Tadin-Strapps M, Stone DJ. TMEM175 deficiency impairs lysosomal and mitochondrial function and increases alpha-synuclein aggregation. Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2389-2394. doi:, 10.1073/pnas.1616332114. Epub 2017 Feb 13. PMID:28193887 doi:http://dx.doi.org/10.1073/pnas.1616332114
2. ↑ Cang C, Aranda K, Seo YJ, Gasnier B, Ren D. TMEM175 Is an Organelle K(+) Channel Regulating Lysosomal Function. Cell. 2015 Aug 27;162(5):1101-12. doi: 10.1016/j.cell.2015.08.002. PMID:26317472 doi:http://dx.doi.org/10.1016/j.cell.2015.08.002
3. ↑ Lee C, Guo J, Zeng W, Kim S, She J, Cang C, Ren D, Jiang Y. The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture. Nature. 2017 Jul 27;547(7664):472-475. doi: 10.1038/nature23269. Epub 2017 Jul, 19. PMID:28723891 doi:http://dx.doi.org/10.1038/nature23269