Multifunctional protein with controversial molecular functionwhich plays an important role in cell protection against oxidativestress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease. It is involved in neuroprotectivemechanisms like the stabilization of NFE2L2 and PINK1 proteins, malefertility as a positive regulator of androgen signaling pathway as wellas cell growth and transformation through, for instance, the modulationof NF-kappa-B signaling pathway. Has been described as a protein and nucleotide deglycase that catalyzesthe deglycation of the Maillard adducts formed between amino groups ofproteins or nucleotides and reactive carbonyl groups of glyoxals. But this function is rebuted byother works. As a protein deglycase, repairs methylglyoxal- and glyoxal-glycated proteins, and releasesrepaired proteins and lactate or glycolate, respectively. Deglycatescysteine, arginine and lysine residues in proteins, and thusreactivates these proteins by reversing glycation by glyoxals. Acts onearly glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) thatcause irreversible damage. Also functions as a nucleotide deglycase able torepair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repairsystem named guanine glycation repair (GG repair), dedicated toreversing methylglyoxal and glyoxal damage via nucleotide sanitizationand direct nucleic acid repair. Protects histonesfrom adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin. Ableto remove the glycations and restore histone 3, histone glycationdisrupts both local and global chromatin architecture by alteringhistone-DNA interactions as well as histone acetylation andubiquitination levels. Displays avery low glyoxalase activity that may reflect its deglycase activity. Eliminateshydrogen peroxide and protects cells against hydrogen peroxide-inducedcell death. Required for correct mitochondrialmorphology and function as well as for autophagy of dysfunctionalmitochondria. Plays a role inregulating expression or stability of the mitochondrial uncouplingproteins SLC25A14 and SLC25A27 in dopaminergic neurons of thesubstantia nigra pars compacta and attenuates the oxidative stressinduced by calcium entry into the neurons via L-type channels duringpacemaking. Regulates astrocyte inflammatoryresponses, may modulate lipid rafts-dependent endocytosis in astrocytesand neuronal cells. In pancreatic islets, involved inthe maintenance of mitochondrial reactive oxygen species (ROS) levelsand glucose homeostasis in an age- and diet dependent manner. Protectspancreatic beta cells from cell death induced by inflammatory andcytotoxic setting. Binds to a number of mRNAscontaining multiple copies of GG or CC motifs and partially inhibitstheir translation but dissociates following oxidative stress. Metal-binding protein able to bind copper as well astoxic mercury ions, enhances the cell protection mechanism againstinduced metal toxicity. In macrophages, interactswith the NADPH oxidase subunit NCF1 to direct NADPH oxidase-dependentROS production, and protects against sepsis. [1-15]

MASKRALVILAKGAEEMETVIPVDVMRRAGIKVTVAGLAGKDPVQCSRDVVICPDASLEDAKKEGPYDVVVLPGGNLGAQNLSESAAVKEILKEQENRKGLIAAICAGPTALLAHEIGFGSKVTTHPLAKDKMMNGGHYTYSENRVEKDGLILTSRGPGTSFEFALAIVEALNGKEVAAQVKAPLVLKD