| 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. 1. Shimura, H. et al. (2000) Nature genetics 25, 302-5. PMID: 108888782. Imai, Y. et al. (2000) The Journal of biological chemistry 275, 35661-4. PMID: 109739423. Shimura, H. et al. (2001) Science (New York, N.Y.) 293, 263-9. PMID: 114315336. Chung, KK. et al. (2004) Science (New York, N.Y.) 304, 1328-31. PMID: 151054607. Ko, HS. et al. (2005) The Journal of neuroscience : the official journal of the Society for Neuroscience 25, 7968-78. PMID: 16135753 |
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