PARK7 : Parkinsonism associated deglycase
Description
The PARK7 (Parkinsonism associated deglycase) is a protein-coding gene located on chromosome 1.
The PARK7 gene provides instructions for making the DJ-1 protein. This protein is found in many tissues and organs, including the brain. Studies indicate that the DJ-1 protein has several functions, although none are fully understood. One of the protein's functions may be to help protect cells, particularly brain cells, from oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to levels that can damage or kill cells. Additionally, the DJ-1 protein may serve as a chaperone molecule that helps fold newly produced proteins into the proper 3-dimensional shape and helps refold damaged proteins. Like other chaperone molecules, the DJ-1 protein may assist in delivering selected proteins to proteasomes, which are structures within cells that break down unneeded molecules. Researchers suggest that the DJ-1 protein may also play a role in activities that produce and process RNA, a chemical cousin of DNA.
The PARK7 gene encodes the DJ-1 protein, which is involved in a variety of cellular processes, particularly those related to cellular protection from oxidative stress and cell death. DJ-1 acts as an oxidative stress sensor, a redox-sensitive chaperone, and a protease. It is known to stabilize proteins like NFE2L2 and PINK1, involved in neuroprotection. DJ-1 also plays a role in male fertility by regulating androgen signaling, and promotes cell growth and transformation through modulation of the NF-kappa-B pathway. There has been debate regarding DJ-1's function as a deglycase, with some studies suggesting it removes glycations from proteins and nucleotides, while others refute this claim. However, its ability to repair methylglyoxal- and glyoxal-glycated proteins, acting on early glycation intermediates to prevent the formation of damaging advanced glycation endproducts (AGEs), has been established. Additionally, DJ-1 has a role in nucleotide deglycation, particularly in repairing glycated guanine in DNA and RNA, contributing to a major nucleotide repair system called guanine glycation repair (GG repair). Further, DJ-1 protects histones from methylglyoxal adduction, controls the levels of methylglyoxal-derived arginine modifications on chromatin, and removes glycations to restore histone 3, which is important for chromatin structure. Despite having a very low glyoxalase activity, DJ-1 effectively eliminates hydrogen peroxide and protects cells against its toxic effects. DJ-1 is also crucial for maintaining mitochondrial morphology and function, facilitating the autophagy of dysfunctional mitochondria. It regulates the expression or stability of mitochondrial uncoupling proteins, attenuates oxidative stress in dopaminergic neurons, and regulates astrocyte inflammatory responses. DJ-1 is further implicated in maintaining mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in pancreatic islets, protecting pancreatic beta cells from cell death. It interacts with mRNA containing GG or CC motifs, partially inhibiting their translation, and binds to copper and mercury ions, enhancing cell protection against metal toxicity. In macrophages, DJ-1 interacts with NCF1 to direct NADPH oxidase-dependent ROS production and provides protection against sepsis. DJ-1 exists as a homodimer, interacts with various proteins like EFCAB6/DJBP, PIAS2, OTUD7B, BBS1, HIPK1, CLCF1, MTERF, PINK1, PRKN, and NCF1, and forms complexes with EFCAB6/DJBP and AR, as well as with PINK1 and PRKN. Its interaction with NCF1 is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation.
PARK7 is also known as DJ-1, DJ1, GATD2, HEL-S-67p.
