Summary
Specificity
Human, Mouse, Rat
Basic Information
Immunogen
Recombinant human PARK-7 Ala2-Asp189
Specificity
Human, Mouse, Rat
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Purity
>95% as determined by analysis by SDS-PAGE
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.
Target
Full Name
Protein/nucleic acid deglycase DJ-1
Introduction
The product of this gene belongs to the peptidase C56 family of proteins. Diseases associated with PARK7 include Parkinson Disease 7, Autosomal Recessive Early-Onset and Parkinson Disease 6, Early Onset. Among its related pathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Synaptic vesicle cycle. GO annotations related to this gene include protein homodimerization activity and receptor binding.
Alternative Names
DJ1; DJ-1; HEL-S-67p
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).
Biological Process
Activation of protein kinase B activity1 PublicationIC:ParkinsonsUK-UCL
Adult locomotory behaviorIEA:Ensembl
AutophagyIEA:UniProtKB-KW
Cellular detoxification of aldehydeManual Assertion Based On ExperimentIDA:UniProtKB
Cellular detoxification of methylglyoxalManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to glyoxalManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Cellular response to hydrogen peroxideManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to oxidative stressManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Detection of oxidative stressIEA:Ensembl
Detoxification of copper ionManual Assertion Based On ExperimentIMP:UniProtKB
Detoxification of mercury ionManual Assertion Based On ExperimentIMP:UniProtKB
DNA repairManual Assertion Based On ExperimentIDA:UniProtKB
Dopamine uptake involved in synaptic transmissionIEA:Ensembl
Glucose homeostasisISS:UniProtKB
Glutathione deglycationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Glycolate biosynthetic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Glyoxal metabolic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Guanine deglycationManual Assertion Based On ExperimentIDA:UniProtKB
Guanine deglycation, glyoxal removalManual Assertion Based On ExperimentIDA:UniProtKB
Guanine deglycation, methylglyoxal removalManual Assertion Based On ExperimentIDA:UniProtKB
Histone modificationManual Assertion Based On ExperimentIMP:UniProtKB
Hydrogen peroxide metabolic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Inflammatory responseIEA:UniProtKB-KW
Insulin secretionISS:UniProtKB
Lactate biosynthetic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Membrane depolarizationIEA:Ensembl
Membrane hyperpolarizationIEA:Ensembl
Methylglyoxal catabolic process to lactateManual Assertion Based On ExperimentIDA:UniProtKB
Methylglyoxal metabolic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Mitochondrion organizationISS:UniProtKB
Negative regulation of apoptotic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of cell deathManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of death-inducing signaling complex assembly1 PublicationIC:ParkinsonsUK-UCL
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Negative regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of gene expressionManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of hydrogen peroxide-induced cell deathManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of hydrogen peroxide-induced neuron deathManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Negative regulation of neuron apoptotic processManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of neuron deathManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of oxidative stress-induced cell deathManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of proteasomal ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of protein acetylationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of protein bindingManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of protein export from nucleusManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Negative regulation of protein K48-linked deubiquitinationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of protein kinase activityManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Negative regulation of protein phosphorylationManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Negative regulation of protein sumoylationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of protein ubiquitinationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of reactive oxygen species biosynthetic processISS:UniProtKB
Biological Process negative regulation of TRAIL-activated apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of ubiquitin-protein transferase activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of ubiquitin-specific protease activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Peptidyl-arginine deglycationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Peptidyl-cysteine deglycationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Peptidyl-lysine deglycationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of acute inflammatory response to antigenic stimulusISS:UniProtKB
Positive regulation of androgen receptor activityManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of autophagy of mitochondrion1 PublicationNAS:ParkinsonsUK-UCL
Positive regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of dopamine biosynthetic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of gene expressionManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Positive regulation of interleukin-8 productionManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of L-dopa biosynthetic processManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of L-dopa decarboxylase activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of mitochondrial electron transport, NADH to ubiquinoneManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of NAD(P)H oxidase activityISS:UniProtKB
Positive regulation of oxidative phosphorylation uncoupler activityIEA:Ensembl
Positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathwayIEA:Ensembl
Positive regulation of peptidyl-serine phosphorylationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of protein kinase B signaling1 PublicationIC:ParkinsonsUK-UCL
Positive regulation of protein localization to nucleusManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of protein-containing complex assemblyManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of pyrroline-5-carboxylate reductase activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of reactive oxygen species biosynthetic processIEA:Ensembl
Positive regulation of superoxide dismutase activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of transcription regulatory region DNA bindingManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of tyrosine 3-monooxygenase activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Protein deglycation, glyoxal removalManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Protein deglycation, methylglyoxal removalManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Protein deglycosylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein stabilizationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Ras protein signal transductionManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Regulation of androgen receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of histone acetylationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of histone ubiquitinationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of inflammatory responseISS:UniProtKB
Regulation of mitochondrial membrane potentialManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of neuron apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of supramolecular fiber organizationManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Single fertilizationIEA:UniProtKB-KW
Cellular Location
Cell membrane
Cytoplasm
Nucleus
Membrane raft
Mitochondrion
Endoplasmic reticulum
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 (PubMed:18711745).
Detected in tau inclusions in brains from neurodegenerative disease patients (PubMed:14705119).
Membrane raft localization in astrocytes and neuronal cells requires palmitoylation.
Involvement in disease
Parkinson disease 7 (PARK7):
A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease).
PTM
Sumoylated on Lys-130 by PIAS2 or PIAS4; which is enhanced after ultraviolet irradiation and essential for cell-growth promoting activity and transforming activity.
Cys-106 is easily oxidized to sulfinic acid.
Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.