Filter By Product Search for
PARK2
Loading...
PARK2 Full Name
parkin RBR E3 ubiquitin protein ligase
PARK2 Introduction
PARK2, officially designated as "parkin RBR E3 ubiquitin protein ligase," is a key gene encoding the Parkin protein—a conserved E3 ubiquitin ligase with pivotal roles in cellular homeostasis, mitochondrial quality control, and immune regulation. Mutations in PARK2 are strongly associated with early-onset Parkinson's disease (PD) and have been linked to multiple pathological processes, including neurodegeneration, oxidative stress, and tumor progression. This page provides a comprehensive overview of PARK2, covering its genetic and protein structure, physiological functions, disease correlations, and current research directions.
Figure 1.Model for PARK2/Parkin recruitment to damaged mitochondria by phosphorylated polyubiquitin chains.
Protein Structure and Post-Translational Modification
The PARK2 gene encodes the Parkin protein, a 52 kDa E3 ubiquitin ligase primarily localized in the cytoplasm and mitochondria. Structurally, Parkin belongs to the RING-between-RING (RBR) family of E3 ligases, characterized by three core domains: an N-terminal ubiquitin-like (Ubl) domain, a central RBR motif (comprising RING1, in-between-RING (IBR), and RING2 subdomains), and a C-terminal domain. The RBR motif is essential for Parkin's enzymatic activity, mediating the transfer of ubiquitin from E2 ubiquitin-conjugating enzymes to target proteins. Post-translational modifications, particularly phosphorylation by PTEN-induced kinase 1 (PINK1), are critical for Parkin activation. Mitochondrial damage triggers PINK1 accumulation on the outer mitochondrial membrane, which phosphorylates and activates Parkin, initiating its translocation to mitochondria.
Immune Regulation in Tumor Microenvironment
Emerging evidence reveals a novel role of Parkin in tumor immune regulation. In tumor-associated macrophages (TAMs), AMPK-dependent activation of Parkin suppresses macrophage antigen presentation by downregulating MHC-I expression via ATG5-dependent autophagy. This impairment of antigen presentation inhibits T cell activation and infiltration, promoting tumor immune escape. Parkin knockout in mice significantly inhibits tumor growth, highlighting its potential as a therapeutic target for cancer immunotherapy.
Alternate Names for PARK2
PARK2
parkin RBR E3 ubiquitin protein ligase
PDJ
PRKN
AR-JP
LPRS2
E3 ubiquitin-protein ligase parkin
parkinson juvenile disease protein 2
parkinson protein 2, E3 ubiquitin protein ligase (parkin)
Parkinson disease (autosomal recessive, juvenile) 2, parkin
