Proteome - SMDBP000250 ( Q99497 )
Description
- IDSMDBP000250
- NameParkinson disease protein 7 (Maillard deglycase) (Oncogene DJ1) (Parkinsonism-associated deglycase) (Protein DJ-1) (DJ-1) (Protein/nucleic acid deglycase DJ-1) (EC 3.1.2.-) (EC 3.5.1.-) (EC 3.5.1.124)
- OrganismHomo sapiens (Human)
- Gene SymbolPARK7
- Gene SynonymsDJ-1; DJ1; GATD2; HEL-S-67p
- ChromosomeGRCh38 chr1:7961654-7985505; hg19 chr1:8021714-8045565
- Protein Sequence
MASKRALVILAKGAEEMETVIPVDVMRRAGIKVTVAGLAGKDPVQCSRDVVICPDASLEDAKKEGPYDVVVLPGGNLGAQNLSESAAVKEILKEQENRKGLIAAICAGPTALLAHEIGFGSKVTTHPLAKDKMMNGGHYTYSENRVEKDGLILTSRGPGTSFEFALAIVEALNGKEVAAQVKAPLVLKD
- Protein Length189
- Mass19891.0
External Links
- UniprotQ99497
- HGNC16369
- HPAENSG00000116288
- GeneCardsPARK7
Expression
- Abundance
Export
Loci
- Sperm LociPostequatorial region
Sperm Loci
Immunocytochemistry of washed motile ejaculated human spermatozoa incubated with antibodies against epididymal secretory proteins and testicular proteins (right panels, merged micrographs of fluorescence staining). Red staining (by PI) indicates the nuclei and green staining (by FITC) indicates the location of HEL-S-67p on spermatozoa. Each bar represents 5 um.
Biological Properties
- General FunctionMultifunctional 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). {ECO:0000250|UniProtKB:Q99LX0, ECO:0000269|PubMed:11477070, ECO:0000269|PubMed:12612053, ECO:0000269|PubMed:12855764, ECO:0000269|PubMed:12939276, ECO:0000269|PubMed:14749723, ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:17015834, ECO:0000269|PubMed:18626009, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20186336, ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23792957, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:25416785, ECO:0000269|PubMed:26995087, ECO:0000269|PubMed:28013050, ECO:0000269|PubMed:28596309, ECO:0000269|PubMed:28993701, ECO:0000269|PubMed:30150385, ECO:0000269|PubMed:30894531, ECO:0000269|PubMed:9070310}.
- GO – Biological Processactivation of protein kinase B activity [GO:0032148]; adult locomotory behavior [GO:0008344]; autophagy [GO:0006914]; cellular detoxification of aldehyde [GO:0110095]; cellular detoxification of methylglyoxal [GO:0140041]; cellular response to glyoxal [GO:0036471]; cellular response to hydrogen peroxide [GO:0070301]; cellular response to oxidative stress [GO:0034599]; detection of oxidative stress [GO:0070994]; detoxification of copper ion [GO:0010273]; detoxification of mercury ion [GO:0050787]; DNA repair [GO:0006281]; dopamine uptake involved in synaptic transmission [GO:0051583]; glucose homeostasis [GO:0042593]; glutathione deglycation [GO:0036531]; glycolate biosynthetic process [GO:0046295]; glyoxal metabolic process [GO:1903189]; guanine deglycation [GO:0106044]; guanine deglycation, glyoxal removal [GO:0106046]; guanine deglycation, methylglyoxal removal [GO:0106045]; histone modification [GO:0016570]; hydrogen peroxide metabolic process [GO:0042743]; inflammatory response [GO:0006954]; insulin secretion [GO:0030073]; lactate biosynthetic process [GO:0019249]; membrane depolarization [GO:0051899]; membrane hyperpolarization [GO:0060081]; methylglyoxal catabolic process to lactate [GO:0061727]; methylglyoxal metabolic process [GO:0009438]; mitochondrion organization [GO:0007005]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cell death [GO:0060548]; negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway [GO:2001268]; negative regulation of death-inducing signaling complex assembly [GO:1903073]; negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway [GO:1902236]; negative regulation of extrinsic apoptotic signaling pathway [GO:2001237]; negative regulation of gene expression [GO:0010629]; negative regulation of hydrogen peroxide-induced cell death [GO:1903206]; negative regulation of hydrogen peroxide-induced neuron death [GO:1903208]; negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway [GO:1903384]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of neuron death [GO:1901215]; negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway [GO:1905259]; negative regulation of oxidative stress-induced cell death [GO:1903202]; negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway [GO:1903377]; negative regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032435]; negative regulation of protein acetylation [GO:1901984]; negative regulation of protein binding [GO:0032091]; negative regulation of protein export from nucleus [GO:0046826]; negative regulation of protein K48-linked deubiquitination [GO:1903094]; negative regulation of protein kinase activity [GO:0006469]; negative regulation of protein phosphorylation [GO:0001933]; negative regulation of protein sumoylation [GO:0033234]; negative regulation of protein ubiquitination [GO:0031397]; negative regulation of reactive oxygen species biosynthetic process [GO:1903427]; negative regulation of TRAIL-activated apoptotic signaling pathway [GO:1903122]; negative regulation of ubiquitin-protein transferase activity [GO:0051444]; negative regulation of ubiquitin-specific protease activity [GO:2000157]; peptidyl-arginine deglycation [GO:0036527]; peptidyl-cysteine deglycation [GO:0036526]; peptidyl-lysine deglycation [GO:0036528]; positive regulation of acute inflammatory response to antigenic stimulus [GO:0002866]; positive regulation of androgen receptor activity [GO:2000825]; positive regulation of autophagy of mitochondrion [GO:1903599]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of dopamine biosynthetic process [GO:1903181]; positive regulation of gene expression [GO:0010628]; positive regulation of interleukin-8 production [GO:0032757]; positive regulation of L-dopa biosynthetic process [GO:1903197]; positive regulation of L-dopa decarboxylase activity [GO:1903200]; positive regulation of mitochondrial electron transport, NADH to ubiquinone [GO:1902958]; positive regulation of NAD(P)H oxidase activity [GO:0033864]; positive regulation of oxidative phosphorylation uncoupler activity [GO:2000277]; positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway [GO:1902177]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of protein-containing complex assembly [GO:0031334]; positive regulation of protein kinase B signaling [GO:0051897]; positive regulation of protein localization to nucleus [GO:1900182]; positive regulation of pyrroline-5-carboxylate reductase activity [GO:1903168]; positive regulation of reactive oxygen species biosynthetic process [GO:1903428]; positive regulation of superoxide dismutase activity [GO:1901671]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of transcription regulatory region DNA binding [GO:2000679]; positive regulation of tyrosine 3-monooxygenase activity [GO:1903178]; protein deglycation, glyoxal removal [GO:0036529]; protein deglycation, methylglyoxal removal [GO:0036530]; protein deglycosylation [GO:0006517]; protein stabilization [GO:0050821]; Ras protein signal transduction [GO:0007265]; regulation of androgen receptor signaling pathway [GO:0060765]; regulation of histone acetylation [GO:0035065]; regulation of histone ubiquitination [GO:0033182]; regulation of inflammatory response [GO:0050727]; regulation of mitochondrial membrane potential [GO:0051881]; regulation of neuron apoptotic process [GO:0043523]; regulation of supramolecular fiber organization [GO:1902903]; single fertilization [GO:0007338]
- GO – Cellular Componentadherens junction [GO:0005912]; axon [GO:0030424]; cell body [GO:0044297]; chromatin [GO:0000785]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; endoplasmic reticulum [GO:0005783]; extracellular exosome [GO:0070062]; membrane raft [GO:0045121]; mitochondrial intermembrane space [GO:0005758]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; PML body [GO:0016605]; presynapse [GO:0098793]
- GO – Molecular Functionandrogen receptor binding [GO:0050681]; cadherin binding [GO:0045296]; copper ion binding [GO:0005507]; cupric ion binding [GO:1903135]; cuprous ion binding [GO:1903136]; cytokine binding [GO:0019955]; DNA-binding transcription factor binding [GO:0140297]; enzyme binding [GO:0019899]; glyoxalase (glycolic acid-forming) activity [GO:1990422]; identical protein binding [GO:0042802]; kinase binding [GO:0019900]; L-dopa decarboxylase activator activity [GO:0036478]; mercury ion binding [GO:0045340]; mRNA binding [GO:0003729]; oxidoreductase activity, acting on peroxide as acceptor [GO:0016684]; oxygen sensor activity [GO:0019826]; peptidase activity [GO:0008233]; peroxiredoxin activity [GO:0051920]; protein-containing complex binding [GO:0044877]; protein deglycase activity [GO:0036524]; protein homodimerization activity [GO:0042803]; scaffold protein binding [GO:0097110]; signaling receptor binding [GO:0005102]; small protein activating enzyme binding [GO:0044388]; superoxide dismutase copper chaperone activity [GO:0016532]; transcription coactivator activity [GO:0003713]; tyrosine 3-monooxygenase activator activity [GO:0036470]; ubiquitin-like protein conjugating enzyme binding [GO:0044390]; ubiquitin-specific protease binding [GO:1990381]