Parkinson disease protein 7 (Q99497)

Uniprot ID	Q99497
Protein Name	Parkinson disease protein 7
Gene Name	PARK7
Species	Homo sapiens (Human)

Signal peptide^(a)	N	Secretome P^(b)
Function	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:17015834, PubMed:20304780, PubMed:18711745, PubMed:12796482, PubMed:19229105, PubMed:25416785, PubMed:26995087, PubMed:28993701). 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:12612053, PubMed:15502874, PubMed:14749723, PubMed:17015834, PubMed:21097510, PubMed:18711745). 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 (PubMed:25416785, PubMed:28596309). But this function is rebuted by other works (PubMed:27903648, PubMed:31653696). 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 (PubMed:25416785, PubMed:28013050, PubMed:26995087). 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 (PubMed:28596309). Protects histones from adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin (PubMed:30150385). 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 (PubMed:30150385, PubMed:30894531). Displays a very low glyoxalase activity that may reflect its deglycase activity (PubMed:22523093, PubMed:31653696, PubMed:28993701). Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death (PubMed:16390825). Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria (PubMed:19229105, PubMed:16632486). 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:18711745). Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells (PubMed:23847046). 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 (By similarity). Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress (PubMed:18626009). 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 (By similarity). .
GO - Molecular function	androgen receptor binding : IPI:ParkinsonsUK-UCL cadherin binding : HDA:BHF-UCL copper ion binding : IDA:UniProtKB cupric ion binding : IDA:ParkinsonsUK-UCL cuprous ion binding : IDA:ParkinsonsUK-UCL cytokine binding : IPI:ParkinsonsUK-UCL enzyme binding : IPI:ParkinsonsUK-UCL identical protein binding : IPI:IntAct kinase binding : IPI:UniProtKB L-dopa decarboxylase activator activity : IDA:ParkinsonsUK-UCL mercury ion binding : IDA:UniProtKB mRNA binding : IDA:UniProtKB oxidoreductase activity, acting on peroxide as acceptor : IDA:ParkinsonsUK-UCL peptidase activity : IDA:UniProtKB peroxiredoxin activity : IEA:Ensembl protein deglycase activity : IDA:ParkinsonsUK-UCL protein homodimerization activity : IDA:UniProtKB protein-containing complex binding : IDA:ParkinsonsUK-UCL repressing transcription factor binding : IPI:ParkinsonsUK-UCL scaffold protein binding : IPI:ParkinsonsUK-UCL signaling receptor binding : IPI:UniProtKB small protein activating enzyme binding : IPI:ParkinsonsUK-UCL superoxide dismutase copper chaperone activity : IDA:ParkinsonsUK-UCL transcription coactivator activity : IGI:ParkinsonsUK-UCL transcription factor binding : IPI:ParkinsonsUK-UCL tyrosine 3-monooxygenase activator activity : IDA:ParkinsonsUK-UCL ubiquitin-like protein conjugating enzyme binding : IPI:ParkinsonsUK-UCL ubiquitin-specific protease binding : IPI:ParkinsonsUK-UCL
GO - Biological process	activation of protein kinase B activity : IC:ParkinsonsUK-UCL adult locomotory behavior : IEA:Ensembl autophagy : IEA:UniProtKB-KW cellular response to glyoxal : IDA:ParkinsonsUK-UCL cellular response to hydrogen peroxide : IDA:UniProtKB cellular response to oxidative stress : IDA:ParkinsonsUK-UCL detoxification of copper ion : IMP:UniProtKB detoxification of mercury ion : IMP:UniProtKB DNA repair : IDA:UniProtKB dopamine uptake involved in synaptic transmission : IEA:Ensembl enzyme active site formation via L-cysteine sulfinic acid : IEA:Ensembl glucose homeostasis : ISS:UniProtKB glutathione deglycation : IDA:ParkinsonsUK-UCL glycolate biosynthetic process : IDA:ParkinsonsUK-UCL glyoxal metabolic process : IDA:ParkinsonsUK-UCL guanine deglycation : IDA:UniProtKB guanine deglycation, glyoxal removal : IDA:UniProtKB guanine deglycation, methylglyoxal removal : IDA:UniProtKB histone modification : IMP:UniProtKB hydrogen peroxide metabolic process : IDA:ParkinsonsUK-UCL inflammatory response : IEA:UniProtKB-KW insulin secretion : ISS:UniProtKB lactate biosynthetic process : IDA:ParkinsonsUK-UCL membrane depolarization : IEA:Ensembl membrane hyperpolarization : IEA:Ensembl methylglyoxal metabolic process : IDA:ParkinsonsUK-UCL mitochondrion organization : ISS:UniProtKB negative regulation of apoptotic process : IDA:ParkinsonsUK-UCL negative regulation of cell death : IDA:UniProtKB negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway : IMP:ParkinsonsUK-UCL negative regulation of death-inducing signaling complex assembly : IC:ParkinsonsUK-UCL negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway : IGI:ParkinsonsUK-UCL negative regulation of extrinsic apoptotic signaling pathway : IMP:UniProtKB negative regulation of gene expression : IDA:ParkinsonsUK-UCL negative regulation of hydrogen peroxide-induced cell death : IMP:ParkinsonsUK-UCL negative regulation of hydrogen peroxide-induced neuron death : IDA:ParkinsonsUK-UCL negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway : IGI:ParkinsonsUK-UCL negative regulation of neuron apoptotic process : IDA:BHF-UCL negative regulation of neuron death : IDA:ParkinsonsUK-UCL negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway : IDA:ParkinsonsUK-UCL negative regulation of oxidative stress-induced cell death : IDA:ParkinsonsUK-UCL negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway : IDA:ParkinsonsUK-UCL negative regulation of proteasomal ubiquitin-dependent protein catabolic process : IDA:ParkinsonsUK-UCL negative regulation of protein acetylation : IDA:ParkinsonsUK-UCL negative regulation of protein binding : IDA:UniProtKB negative regulation of protein export from nucleus : IGI:ParkinsonsUK-UCL negative regulation of protein K48-linked deubiquitination : IDA:ParkinsonsUK-UCL negative regulation of protein kinase activity : IGI:ParkinsonsUK-UCL negative regulation of protein phosphorylation : IGI:ParkinsonsUK-UCL negative regulation of protein sumoylation : IDA:ParkinsonsUK-UCL negative regulation of protein ubiquitination : IDA:ParkinsonsUK-UCL negative regulation of reactive oxygen species biosynthetic process : ISS:UniProtKB negative regulation of TRAIL-activated apoptotic signaling pathway : IMP:ParkinsonsUK-UCL negative regulation of ubiquitin-protein transferase activity : IDA:ParkinsonsUK-UCL negative regulation of ubiquitin-specific protease activity : IDA:ParkinsonsUK-UCL peptidyl-arginine deglycation : IDA:ParkinsonsUK-UCL peptidyl-cysteine deglycation : IDA:ParkinsonsUK-UCL peptidyl-lysine deglycation : IDA:ParkinsonsUK-UCL positive regulation of acute inflammatory response to antigenic stimulus : ISS:UniProtKB positive regulation of androgen receptor activity : IMP:ParkinsonsUK-UCL positive regulation of autophagy of mitochondrion : NAS:ParkinsonsUK-UCL positive regulation of DNA-binding transcription factor activity : IMP:ParkinsonsUK-UCL positive regulation of dopamine biosynthetic process : IDA:ParkinsonsUK-UCL positive regulation of gene expression : TAS:ParkinsonsUK-UCL positive regulation of interleukin-8 production : IDA:ParkinsonsUK-UCL positive regulation of L-dopa biosynthetic process : IMP:ParkinsonsUK-UCL positive regulation of L-dopa decarboxylase activity : IDA:ParkinsonsUK-UCL positive regulation of mitochondrial electron transport, NADH to ubiquinone : IMP:ParkinsonsUK-UCL positive regulation of NAD(P)H oxidase activity : ISS:UniProtKB positive regulation of oxidative phosphorylation uncoupler activity : IEA:Ensembl positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway : IEA:Ensembl positive regulation of peptidyl-serine phosphorylation : IMP:ParkinsonsUK-UCL positive regulation of protein kinase B signaling : IC:ParkinsonsUK-UCL positive regulation of protein localization to nucleus : IDA:ParkinsonsUK-UCL positive regulation of protein-containing complex assembly : IDA:ParkinsonsUK-UCL positive regulation of pyrroline-5-carboxylate reductase activity : IDA:ParkinsonsUK-UCL positive regulation of reactive oxygen species biosynthetic process : IEA:Ensembl positive regulation of superoxide dismutase activity : IDA:ParkinsonsUK-UCL positive regulation of transcription by RNA polymerase II : IDA:ParkinsonsUK-UCL positive regulation of transcription regulatory region DNA binding : IMP:ParkinsonsUK-UCL positive regulation of tyrosine 3-monooxygenase activity : IDA:ParkinsonsUK-UCL protein deglycation, glyoxal removal : IDA:ParkinsonsUK-UCL protein deglycation, methylglyoxal removal : IDA:ParkinsonsUK-UCL protein deglycosylation : IDA:UniProtKB protein stabilization : IDA:ParkinsonsUK-UCL Ras protein signal transduction : TAS:ParkinsonsUK-UCL regulation of androgen receptor signaling pathway : IDA:UniProtKB regulation of inflammatory response : ISS:UniProtKB regulation of mitochondrial membrane potential : IMP:ParkinsonsUK-UCL regulation of neuron apoptotic process : IDA:UniProtKB regulation of supramolecular fiber organization : TAS:ParkinsonsUK-UCL single fertilization : IEA:UniProtKB-KW

Back

^{(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.}
^{(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.}