Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease (PubMed:15784737, PubMed:17015834, PubMed:20800516, PubMed:21068725). It is involved in neuroprotective mechanisms like the stabilization of NFE2L2 and PINK1 proteins, male fertility as a positive regulator of androgen signaling pathway as well as cell growth and transformation through, for instance, the modulation of NF-kappa-B signaling pathway (PubMed:17015834, PubMed:21097510). Has been described as a protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals. But this function is rebuted by other works. As a protein deglycase, repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) that cause irreversible damage. Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair. Protects histones from adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin. Able to remove the glycations and restore histone 3, histone glycation disrupts both local and global chromatin architecture by altering histone-DNA interactions as well as histone acetylation and ubiquitination levels. Displays a very low glyoxalase activity that may reflect its deglycase activity (PubMed:22523093). Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death (PubMed:17766438). Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria (PubMed:20186336). Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking (PubMed:21068725). Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells (PubMed:23847046, PubMed:19276172). In pancreatic islets, involved in the maintenance of mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in an age- and diet dependent manner. Protects pancreatic beta cells from cell death induced by inflammatory and cytotoxic setting (PubMed:26422139). Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress (By similarity). Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (PubMed:23792957). In macrophages, interacts with the NADPH oxidase subunit NCF1 to direct NADPH oxidase-dependent ROS production, and protects against sepsis (PubMed:26021615). H2O + N(omega)-(1-hydroxy-2-oxopropyl)-L-arginyl-[protein] = H(+) + L-arginyl-[protein] + lactate H2O + N(6)-(1-hydroxy-2-oxopropyl)-L-lysyl-[protein] = H(+) + L-lysyl-[protein] + lactate H2O + S-(1-hydroxy-2-oxopropyl)-L-cysteinyl-[protein] = H(+) + L-cysteinyl-[protein] + lactate H2O + N(omega)-(1-hydroxy-2-oxoethyl)-L-arginyl-[protein] = glycolate + H(+) + L-arginyl-[protein] H2O + N(6)-(1-hydroxy-2-oxoethyl)-L-lysyl-[protein] = glycolate + H(+) + L-lysyl-[protein] H2O + S-(1-hydroxy-2-oxoethyl)-L-cysteinyl-[protein] = glycolate + H(+) + L-cysteinyl-[protein] H2O + N(2)-(1-hydroxy-2-oxopropyl)-dGTP = dGTP + H(+) + lactate H2O + N(2)-(1-hydroxy-2-oxopropyl)-GTP = GTP + H(+) + lactate H2O + N(2)-(1-hydroxy-2-oxopropyl)-GDP = GDP + H(+) + lactate H2O + N(2)-(1-hydroxy-2-oxopropyl)-GMP = GMP + H(+) + lactate H2O + N(2)-(1-hydroxy-2-oxoethyl)-dGTP = dGTP + glycolate + H(+) H2O + N(2)-(1-hydroxy-2-oxoethyl)-GTP = glycolate + GTP + H(+) H2O + N(2)-(1-hydroxy-2-oxoethyl)-GDP = GDP + glycolate + H(+) H2O + N(2)-(1-hydroxy-2-oxoethyl)-GMP = glycolate + GMP + H(+) an N(2)-(1-hydroxy-2-oxopropyl)-guanosine in RNA + H2O = a guanosine in RNA + H(+) + lactate an N(2)-(1-hydroxy-2-oxopropyl)-2'-deoxyguanosine in DNA + H2O = a 2'-deoxyguanosine in DNA + H(+) + lactate an N(2)-(1-hydroxy-2-oxoethyl)-guanosine in RNA + H2O = a guanosine in RNA + glycolate + H(+) an N(2)-(1-hydroxy-2-oxoethyl)-2'-deoxyguanosine in DNA + H2O = a 2'-deoxyguanosine in DNA + glycolate + H(+) Deglycase activity does not require glutathione as a cofactor, however, glycated glutathione constitutes a PARK7 substrate. Homodimer. Binds EFCAB6/DJBP and PIAS2. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR. Binds to HIPK1 (By similarity). Interacts (via N-terminus) with OTUD7B (PubMed:21097510). Interacts with BBS1, CLCF1 and MTERF (PubMed:21097510). Interacts (via C-terminus) with NCF1; the interaction is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation (PubMed:26021615). Interacts with NENF (PubMed:31536960). Under normal conditions, located predominantly in the cytoplasm and, to a lesser extent, in the nucleus and mitochondrion. Translocates to the mitochondrion and subsequently to the nucleus in response to oxidative stress and exerts an increased cytoprotective effect against oxidative damage (By similarity). Membrane raft localization in astrocytes and neuronal cells requires palmitoylation (PubMed:23847046). Expressed in erythroblasts and in mature red blood cells from peripheral blood (at protein level) (PubMed:20800516). In pancreas, expression is higher in islets than surrounding exocrine tissues (PubMed:22611253). Expression increases during erythroid development (at protein level) (PubMed:20800516). In pancreatic islets, expression increases during aging (PubMed:22611253). By hydrogen peroxide. Sumoylated on Lys-130 by PIAS2 or PIAS4; which is essential for cell-growth promoting activity and transforming activity. Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress. Increased sensitivity of embryonic cortical neurons to oxidative stress. Age-dependent increase in mitochondrial hydrogen peroxide production and reduced mitochondrial aconitase activity. Down-regulation of Slc25a14 and Slc25a27, compromised calcium-induced uncoupling and increased oxidation of mitochondrial matrix proteins specifically in the dopaminergic neurons of the substantia nigra pars compacta. Reduced N2el2 protein expression. Impaired mitochondrial function and morphology with reduced autophagy leading to accumulation of defective mitochondria. Targeted knockouts in astrocytes exhibit augmented LPS-induced CRK/p38 phosphorylation and signaling, they don't stimulate TLR4 endocytosis upon LPS stimulation. Knockout animals present increased bacterial burdens, reduced local and systemic inflammation, macrophage paralysis and impaired induction of pro-inflammatory cytokines, such as IL6 and TNF, under the condition of sepsis (PubMed:26021615). Mutants from 12 weeks old, but not younger, show higher levels of reactive oxygen species (ROS) and mitochondrial fragmentation in pancreatic islets. They have lower levels of plasma insulin after glucose challenge, display glucose intolerance and have reduced beta-cell area. Younger mutants kept on a high fat diet also show lower levels of plasma insulin, display glucose intolerance and have reduced beta-cell area (PubMed:22611253). Animals become diabetic upon multiple low doses of streptozotocin with reduced insulin concentrations, higher fasting blood glucose concentrations and higher rates of beta cell apoptosis compared to wild type (PubMed:26422139). Belongs to the peptidase C56 family. Glyoxalase activity has been reported (PubMed:22523093). It may however reflect its deglycase activity. The protein deglycation activity is controversial. It has been ascribed to a TRIS buffer artifact by a publication and as a result of the removal of methylglyoxal by glyoxalase activity that leads to a subsequent decomposition of hemithioacetals and hemianimals due to the shift in equilibrium position by another one. However, biochemical experiments showing that PARK7 is a bona fide deglycase have been performed.