Names & Taxonomy
- Uniprot ID:
- Q99497
- Entry Name:
- PARK7_HUMAN
- Status:
- reviewed
- Protein Names:
- Protein deglycase DJ-1 (DJ-1) (EC 3.1.2.-) (EC 3.5.1.-) (Oncogene DJ1) (Parkinson disease protein 7)
- Gene Names:
- PARK7
- Gene Names Primary:
- PARK7
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 189
- Sequence:
- MASKRALVILAKGAEEMETVIPVDVMRRAGIKVTVAGLAGKDPVQCSRDVVICPDASLEDAKKEGPYDVVVLPGGNLGAQNLSESAAVKEILKEQENRKGLIAAICAGPTALLAHEIGFGSKVTTHPLAKDKMMNGGHYTYSENRVEKDGLILTSRGPGTSFEFALAIVEALNGKEVAAQVKAPLVLKD
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cell membrane
Function
- Function:
- Protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteines, arginines and lysines 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) (PubMed:25416785). Plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease; functions probably related to its primary function (PubMed:17015834, PubMed:20304780, PubMed:18711745, PubMed:12796482, PubMed:19229105, PubMed:25416785). 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). Its involvement in protein repair could also explain other unrelated functions. 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). 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).
- Cofactor:
- COFACTOR: ; Note=Does not require glutathione as a cofactor, however, glycated glutathione constitutes a PARK7 substrate.
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: ; Kinetic parameters: KM=173.4 uM for casein
- Active Site:
- ACT_SITE 106 106 Nucleophile.
- Gene Ontology Go:
- axon
cell body
chromatin
cytoplasm
cytosol
endoplasmic reticulum
extracellular exosome
membrane raft
mitochondrial intermembrane space
mitochondrial matrix
mitochondrion
nucleus
plasma membrane
PML body
presynapse
androgen receptor binding
copper ion binding
cupric ion binding
cuprous ion binding
cytokine binding
enzyme binding
glyoxalase (glycolic acid-forming) activity
glyoxalase III activity
identical protein binding
kinase binding
L-dopa decarboxylase activator activity
mercury ion binding
mRNA binding
oxidoreductase activity, acting on peroxide as acceptor
peptidase activity
peroxiredoxin activity
protein homodimerization activity
receptor binding
repressing transcription factor binding
scaffold protein binding
small protein activating enzyme binding
superoxide dismutase copper chaperone activity
transcription coactivator activity
transcription factor binding
tyrosine 3-monooxygenase activator activity
ubiquitin-like protein conjugating enzyme binding
ubiquitin-specific protease binding
activation of protein kinase B activity
adult locomotory behavior
autophagy
cellular response to glyoxal
cellular response to hydrogen peroxide
cellular response to oxidative stress
detoxification of copper ion
detoxification of mercury ion
dopamine uptake involved in synaptic transmission
enzyme active site formation via L-cysteine sulfinic acid
glycolate biosynthetic process
glyoxal catabolic process
hydrogen peroxide metabolic process
inflammatory response
lactate biosynthetic process
membrane depolarization
membrane hyperpolarization
methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione
mitochondrion organization
negative regulation of apoptotic process
negative regulation of cell death
negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
negative regulation of death-inducing signaling complex assembly
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
negative regulation of extrinsic apoptotic signaling pathway
negative regulation of gene expression
negative regulation of hydrogen peroxide-induced cell death
negative regulation of hydrogen peroxide-induced neuron death
negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway
negative regulation of neuron apoptotic process
negative regulation of neuron death
negative regulation of oxidative stress-induced cell death
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
negative regulation of proteasomal ubiquitin-dependent protein catabolic process
negative regulation of protein acetylation
negative regulation of protein binding
negative regulation of protein export from nucleus
negative regulation of protein K48-linked deubiquitination
negative regulation of protein kinase activity
negative regulation of protein phosphorylation
negative regulation of protein sumoylation
negative regulation of protein ubiquitination
negative regulation of TRAIL-activated apoptotic signaling pathway
negative regulation of ubiquitin-protein transferase activity
negative regulation of ubiquitin-specific protease activity
positive regulation of androgen receptor activity
positive regulation of dopamine biosynthetic process
positive regulation of gene expression
positive regulation of interleukin-8 production
positive regulation of L-dopa biosynthetic process
positive regulation of L-dopa decarboxylase activity
positive regulation of mitochondrial electron transport, NADH to ubiquinone
positive regulation of mitophagy
positive regulation of oxidative phosphorylation uncoupler activity
positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
positive regulation of peptidyl-serine phosphorylation
positive regulation of protein homodimerization activity
positive regulation of protein kinase B signaling
positive regulation of protein localization to nucleus
positive regulation of pyrroline-5-carboxylate reductase activity
positive regulation of reactive oxygen species biosynthetic process
positive regulation of sequence-specific DNA binding transcription factor activity
positive regulation of superoxide dismutase activity
positive regulation of transcription from RNA polymerase II promoter
positive regulation of transcription regulatory region DNA binding
positive regulation of tyrosine 3-monooxygenase activity
protein deglycosylation
protein stabilization
Ras protein signal transduction
regulation of androgen receptor signaling pathway
regulation of fibril organization
regulation of inflammatory response
regulation of mitochondrial membrane potential
regulation of neuron apoptotic process
response to drug
single fertilization - Gene Ontology Biological Process:
- activation of protein kinase B activity
adult locomotory behavior
autophagy
cellular response to glyoxal
cellular response to hydrogen peroxide
cellular response to oxidative stress
detoxification of copper ion
detoxification of mercury ion
dopamine uptake involved in synaptic transmission
enzyme active site formation via L-cysteine sulfinic acid
glycolate biosynthetic process
glyoxal catabolic process
hydrogen peroxide metabolic process
inflammatory response
lactate biosynthetic process
membrane depolarization
membrane hyperpolarization
methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione
mitochondrion organization
negative regulation of apoptotic process
negative regulation of cell death
negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
negative regulation of death-inducing signaling complex assembly
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
negative regulation of extrinsic apoptotic signaling pathway
negative regulation of gene expression
negative regulation of hydrogen peroxide-induced cell death
negative regulation of hydrogen peroxide-induced neuron death
negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway
negative regulation of neuron apoptotic process
negative regulation of neuron death
negative regulation of oxidative stress-induced cell death
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
negative regulation of proteasomal ubiquitin-dependent protein catabolic process
negative regulation of protein acetylation
negative regulation of protein binding
negative regulation of protein export from nucleus
negative regulation of protein K48-linked deubiquitination
negative regulation of protein kinase activity
negative regulation of protein phosphorylation
negative regulation of protein sumoylation
negative regulation of protein ubiquitination
negative regulation of TRAIL-activated apoptotic signaling pathway
negative regulation of ubiquitin-protein transferase activity
negative regulation of ubiquitin-specific protease activity
positive regulation of androgen receptor activity
positive regulation of dopamine biosynthetic process
positive regulation of gene expression
positive regulation of interleukin-8 production
positive regulation of L-dopa biosynthetic process
positive regulation of L-dopa decarboxylase activity
positive regulation of mitochondrial electron transport, NADH to ubiquinone
positive regulation of mitophagy
positive regulation of oxidative phosphorylation uncoupler activity
positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
positive regulation of peptidyl-serine phosphorylation
positive regulation of protein homodimerization activity
positive regulation of protein kinase B signaling
positive regulation of protein localization to nucleus
positive regulation of pyrroline-5-carboxylate reductase activity
positive regulation of reactive oxygen species biosynthetic process
positive regulation of sequence-specific DNA binding transcription factor activity
positive regulation of superoxide dismutase activity
positive regulation of transcription from RNA polymerase II promoter
positive regulation of transcription regulatory region DNA binding
positive regulation of tyrosine 3-monooxygenase activity
protein deglycosylation
protein stabilization
Ras protein signal transduction
regulation of androgen receptor signaling pathway
regulation of fibril organization
regulation of inflammatory response
regulation of mitochondrial membrane potential
regulation of neuron apoptotic process
response to drug
single fertilization - Gene Ontology Molecular Function:
- androgen receptor binding
copper ion binding
cupric ion binding
cuprous ion binding
cytokine binding
enzyme binding
glyoxalase (glycolic acid-forming) activity
glyoxalase III activity
identical protein binding
kinase binding
L-dopa decarboxylase activator activity
mercury ion binding
mRNA binding
oxidoreductase activity, acting on peroxide as acceptor
peptidase activity
peroxiredoxin activity
protein homodimerization activity
receptor binding
repressing transcription factor binding
scaffold protein binding
small protein activating enzyme binding
superoxide dismutase copper chaperone activity
transcription coactivator activity
transcription factor binding
tyrosine 3-monooxygenase activator activity
ubiquitin-like protein conjugating enzyme binding
ubiquitin-specific protease binding - Gene Ontology Cellular Component:
- axon
cell body
chromatin
cytoplasm
cytosol
endoplasmic reticulum
extracellular exosome
membrane raft
mitochondrial intermembrane space
mitochondrial matrix
mitochondrion
nucleus
plasma membrane
PML body
presynapse - Keywords:
- 3D-structure
Acetylation
Autophagy
Cell membrane
Chaperone
Complete proteome
Copper
Cytoplasm
Direct protein sequencing
Disease mutation
Fertilization
Hydrolase
Inflammatory response
Isopeptide bond
Lipoprotein
Membrane
Mitochondrion
Neurodegeneration
Nucleus
Oxidation
Palmitate
Parkinson disease
Parkinsonism
Phosphoprotein
Polymorphism
Protease
RNA-binding
Reference proteome
Stress response
Tumor suppressor
Ubl conjugation
Zymogen - Interacts With:
- Itself; P10275; Q9UER7; Q13158; P63244; Q9HD26; O94776; Q6GQQ9; P32322
Publication
- PubMed ID:
- 9070310 14702039 16710414 15489334 11223268 11477070 12851414 14713311 12612053 14579415 14705119 14662519 14749723 15502874 15592455 15976810 16390825 17015834 18626009 19229105 18711745 20304780 21269460 21097510 22523093 23847046 23792957 24275569 25416785 25944712 12914946 12761214 12796482 12939276 12855764 15181200 12953260 12446870 14705128 15365989 14607841 15254937 14872018 16240358 16632486 17846173 20186336