E3 ubiquitin-protein ligase parkin (PRKN)

Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2 (PubMed:10973942, PubMed:10888878, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:16135753, PubMed:21376232, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536).

Mediates monoubiquitination and'Lys-6','Lys-11','Lys-48'-connected and'Lys-63'-linked polyubiquitination of substrates depending on the circumstance (PubMed:19229105, PubMed:20889974, PubMed:25621951).

Participates in the elimination and/or detox of abnormally folded or damaged protein by mediating'Lys-63'-linked polyubiquitination of misfolded proteins like PARK7:'Lys-63'- linked polyubiquitinated misfolded proteins are then recognized by HDAC6, resulting in their recruitment to aggresomes, followed by degradation (PubMed:17846173, PubMed:19229105). Mediates'Lys-63'- linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (PubMed:11590439, PubMed:11431533, PubMed:19229105, PubMed:11590439, PubMed:15728840).