PRKN Protein, Mouse (GST)

PRKN functions as a component of a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin to substrate proteins such as SYT11 and VDAC1. Other substrates include BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1, and AIMP2 (by similarity). It mediates monoubiquitination and various polyubiquitination linkages ('Lys-6', 'Lys-11', 'Lys-48', and 'Lys-63') depending on context. PRKN participates in clearing misfolded proteins via 'Lys-63'-linked polyubiquitination, targeting them for aggresome formation and degradation (by similarity). It positively regulates autophagy by monoubiquitinating BCL2 (by similarity). During cellular stress, PRKN acts downstream of PINK1 to maintain mitochondrial health through mechanisms ranging from preventing apoptosis and promoting mitochondrial biogenesis to mediating mitophagy (by similarity). It ubiquitinates mitochondrial proteins like TOMM20, RHOT1/MIRO1, MFN1, and USP30 to facilitate autophagic clearance of damaged mitochondria (by similarity). PRKN also regulates mitochondrial motility by degrading MIRO1/MIRO2 (by similarity) and promotes mitochondrial biogenesis via 'Lys-48'-linked polyubiquitination and degradation of ZNF746/PARIS (by similarity). Independently of its ligase activity, PRKN suppresses apoptosis by transcriptionally repressing p53/TP53 (by similarity).