| 背景 | E3 ubiquitin-protein ligase parkin (PRKN) is a ~51 kDa protein. Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Substrates include SYT11 and VDAC1. Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. 2. Ham, SJ. et al. (2020) Proceedings of the National Academy of Sciences of the United States of America 117, 4281-4291. PMID: 320470333. Shiba-Fukushima, K. et al. (2014) PLoS genetics 10, e1004861. PMID: 254740074. Kuroda, Y. et al. (2012) Human molecular genetics 21, 991-1003. PMID: 22082830 |
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