PRKN Protein, Human (sf9, His, Myc)

Parkin is a component of a multiprotein E3 ubiquitin ligase complex that catalyzes the covalent attachment of ubiquitin moieties to substrate proteins, including SYT11, VDAC1, BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1, and AIMP2. It mediates monoubiquitination as well as context-dependent 'Lys-6'-, 'Lys-11'-, 'Lys-48'-, and 'Lys-63'-linked polyubiquitination. Parkin participates in the removal or detoxification of misfolded or damaged proteins by mediating 'Lys-63'-linked polyubiquitination, leading to their recruitment to aggresomes and subsequent degradation. It also plays a role in Lewy-body formation through 'Lys-63'-linked polyubiquitination of SNCAIP. During cellular stress, Parkin acts downstream of PINK1 to protect mitochondrial function by coordinating quality control mechanisms, ranging from preventing apoptosis and stimulating mitochondrial biogenesis to regulating dynamics and eliminating damaged mitochondria via mitophagy. Together with PINK1, Parkin mediates the decision between mitophagy and apoptosis inhibition by ubiquitinating VDAC1. It regulates mitochondrial motility by ubiquitinating and degrading MIRO1 and MIRO2 and promotes mitochondrial biogenesis by degrading the transcriptional repressor ZNF746/PARIS via 'Lys-48'-linked polyubiquitination. Parkin also limits reactive oxygen species (ROS) production, regulates cyclin-E during neuronal apoptosis, and independently of its ubiquitin ligase activity, protects against apoptosis by transcriptionally repressing p53/TP53.