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Protein

Protein/nucleic acid deglycase DJ-1

Gene

Park7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Thus, functions as a protein deglycase that 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. 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 (By similarity). Also displays an apparent glyoxalase activity that in fact reflects its deglycase activity (PubMed:22523093). 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:15784737, PubMed:17015834, PubMed:20800516, PubMed:21068725). 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:17015834, PubMed:21097510). Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death (PubMed:17766438). Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria (PubMed:20186336). 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:21068725). Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells (PubMed:23847046, PubMed:19276172). In pancreatic islets, involved in the maintenance of mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in an age- and diet dependent manner (PubMed:22611253). Protects pancreatic beta cells from cell death induced by inflammatory and cytotoxic setting (PubMed:26422139). Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress (By similarity). 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 (PubMed:26021615).By similarity13 Publications

Caution

Glyoxylase activity previously reported may reflect in fact its deglycase activity (PubMed:22523093).By similarity1 Publication
The protein deglycation activity has been ascribed to a TRIS buffer artifact by a publication, which has then been rebutted by clear biochemical experiments showing that PARK7 is a bona fide deglycase. Deglycase activity is even strengthened by a novel article that reports nucleotide deglycation activity.By similarity

Catalytic activityi

An N(omega)-(1-hydroxy-2-oxopropyl)-[protein]-L-arginine + H2O = a [protein]-L-arginine + (R)-lactate.By similarity
An N6-(1-hydroxy-2-oxopropyl)-[protein]-L-lysine + H2O = a [protein]-L-lysine + (R)-lactate.By similarity
An S-(1-hydroxy-2-oxopropyl)-[protein]-L-cysteine + H2O = a [protein]-L-cysteine + (R)-lactate.By similarity

Cofactori

Note: Deglycase activity does not require glutathione as a cofactor, however, glycated glutathione constitutes a PARK7 substrate.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei106NucleophileBy similarity1
Active sitei126By similarity1

GO - Molecular functioni

GO - Biological processi

  • adult locomotory behavior Source: MGI
  • autophagy Source: UniProtKB-KW
  • cell proliferation Source: MGI
  • cellular response to glyoxal Source: ParkinsonsUK-UCL
  • cellular response to hydrogen peroxide Source: UniProtKB
  • cellular response to oxidative stress Source: UniProtKB
  • cellular response to reactive oxygen species Source: MGI
  • detoxification of copper ion Source: UniProtKB
  • detoxification of mercury ion Source: UniProtKB
  • DNA repair Source: UniProtKB
  • dopamine uptake involved in synaptic transmission Source: MGI
  • enzyme active site formation via L-cysteine sulfinic acid Source: ParkinsonsUK-UCL
  • glucose homeostasis Source: UniProtKB
  • glutathione deglycation Source: MGI
  • glycolate biosynthetic process Source: ParkinsonsUK-UCL
  • glyoxal metabolic process Source: ParkinsonsUK-UCL
  • guanine deglycation Source: UniProtKB
  • guanine deglycation, glyoxal removal Source: UniProtKB
  • guanine deglycation, methylglyoxal removal Source: UniProtKB
  • hydrogen peroxide metabolic process Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • insulin secretion Source: UniProtKB
  • lactate biosynthetic process Source: MGI
  • membrane depolarization Source: MGI
  • membrane hyperpolarization Source: MGI
  • mitochondrion organization Source: UniProtKB
  • negative regulation of apoptotic process Source: ParkinsonsUK-UCL
  • negative regulation of cell death Source: UniProtKB
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: MGI
  • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • negative regulation of extrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of gene expression Source: MGI
  • negative regulation of hydrogen peroxide-induced cell death Source: MGI
  • negative regulation of hydrogen peroxide-induced neuron death Source: ParkinsonsUK-UCL
  • negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • negative regulation of neuron apoptotic process Source: MGI
  • negative regulation of neuron death Source: MGI
  • negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of oxidative stress-induced cell death Source: MGI
  • negative regulation of oxidative stress-induced neuron death Source: ParkinsonsUK-UCL
  • negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • negative regulation of protein acetylation Source: MGI
  • negative regulation of protein binding Source: UniProtKB
  • negative regulation of protein catabolic process Source: ParkinsonsUK-UCL
  • negative regulation of protein export from nucleus Source: MGI
  • negative regulation of protein K48-linked deubiquitination Source: MGI
  • negative regulation of protein kinase activity Source: MGI
  • negative regulation of protein phosphorylation Source: MGI
  • negative regulation of protein sumoylation Source: MGI
  • negative regulation of protein ubiquitination Source: ParkinsonsUK-UCL
  • negative regulation of reactive oxygen species biosynthetic process Source: UniProtKB
  • negative regulation of TRAIL-activated apoptotic signaling pathway Source: MGI
  • negative regulation of ubiquitin-protein transferase activity Source: MGI
  • negative regulation of ubiquitin-specific protease activity Source: MGI
  • peptidyl-arginine deglycation Source: MGI
  • peptidyl-cysteine deglycation Source: MGI
  • peptidyl-lysine deglycation Source: MGI
  • positive regulation of acute inflammatory response to antigenic stimulus Source: UniProtKB
  • positive regulation of androgen receptor activity Source: MGI
  • positive regulation of DNA binding transcription factor activity Source: MGI
  • positive regulation of dopamine biosynthetic process Source: MGI
  • positive regulation of gene expression Source: ParkinsonsUK-UCL
  • positive regulation of interleukin-8 production Source: MGI
  • positive regulation of L-dopa biosynthetic process Source: MGI
  • positive regulation of L-dopa decarboxylase activity Source: MGI
  • positive regulation of mitochondrial electron transport, NADH to ubiquinone Source: ParkinsonsUK-UCL
  • positive regulation of NAD(P)H oxidase activity Source: UniProtKB
  • positive regulation of oxidative phosphorylation uncoupler activity Source: UniProtKB
  • positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: MGI
  • positive regulation of peptidyl-serine phosphorylation Source: MGI
  • positive regulation of protein homodimerization activity Source: MGI
  • positive regulation of protein localization to nucleus Source: MGI
  • positive regulation of pyrroline-5-carboxylate reductase activity Source: MGI
  • positive regulation of reactive oxygen species biosynthetic process Source: MGI
  • positive regulation of superoxide dismutase activity Source: MGI
  • positive regulation of transcription by RNA polymerase II Source: ParkinsonsUK-UCL
  • positive regulation of transcription regulatory region DNA binding Source: MGI
  • positive regulation of tyrosine 3-monooxygenase activity Source: MGI
  • protein deglycation, glyoxal removal Source: MGI
  • protein deglycosylation Source: UniProtKB
  • protein stabilization Source: UniProtKB
  • regulation of androgen receptor signaling pathway Source: MGI
  • regulation of inflammatory response Source: UniProtKB
  • regulation of mitochondrial membrane potential Source: MGI
  • regulation of neuron apoptotic process Source: UniProtKB
  • response to hydrogen peroxide Source: MGI
  • single fertilization Source: UniProtKB-KW
  • synaptic transmission, dopaminergic Source: MGI

Keywordsi

Molecular functionChaperone, Hydrolase, Protease, RNA-binding
Biological processAutophagy, DNA damage, DNA repair, Fertilization, Inflammatory response, Stress response
LigandCopper

Protein family/group databases

MEROPSiC56.002

Names & Taxonomyi

Protein namesi
Recommended name:
Protein/nucleic acid deglycase DJ-1By similarity (EC:3.1.2.-By similarity, EC:3.5.1.-By similarity, EC:3.5.1.124By similarity)
Alternative name(s):
Maillard deglycaseBy similarity
Parkinson disease protein 7 homologCurated
Parkinsonism-associated deglycaseBy similarity
Protein DJ-1Curated
Short name:
DJ-1
Gene namesi
Name:Park7Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:2135637 Park7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Disruption phenotypei

Increased sensitivity of embryonic cortical neurons to oxidative stress. Age-dependent increase in mitochondrial hydrogen peroxide production and reduced mitochondrial aconitase activity. Down-regulation of Slc25a14 and Slc25a27, compromised calcium-induced uncoupling and increased oxidation of mitochondrial matrix proteins specifically in the dopaminergic neurons of the substantia nigra pars compacta. Reduced N2el2 protein expression. Impaired mitochondrial function and morphology with reduced autophagy leading to accumulation of defective mitochondria. Targeted knockouts in astrocytes exhibit augmented LPS-induced CRK/p38 phosphorylation and signaling, they don't stimulate TLR4 endocytosis upon LPS stimulation. Knockout animals present increased bacterial burdens, reduced local and systemic inflammation, macrophage paralysis and impaired induction of proinflammatory cytokines, such as IL6 and TNF, under the condition of sepsis (PubMed:26021615). Mutants from 12 weeks old, but not younger, show higher levels of reactive oxygen species (ROS) and mitochondrial fragmentation in pancreatic islets. They have lower levels of plasma insulin after glucose challenge, display glucose intolerance and have reduced beta-cell area. Younger mutants kept on a high fat diet also show lower levels of plasma insulin, display glucose intolerance and have reduced beta-cell area (PubMed:22611253). Animals become diabetic upon multiple low doses of streptozotocin with reduced insulin concentrations, higher fasting blood glucose concentrations and higher rates of beta cell apoptosis compared to wild type (PubMed:26422139).9 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi46C → A: Sulfinic acid detected following treatment with hydrogen peroxide. 1 Publication1
Mutagenesisi53C → A: Sulfinic acid detected following treatment with hydrogen peroxide. 1 Publication1
Mutagenesisi106C → A: No sulfinic acid detected following treatment with hydrogen peroxide. 1 Publication1

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_0000405560? – 189Removed in mature form
Initiator methionineiRemovedBy similarity
ChainiPRO_00001578502 – ?Protein/nucleic acid deglycase DJ-1

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Lipidationi46S-palmitoyl cysteineBy similarity1
Lipidationi53S-palmitoyl cysteineBy similarity1
Modified residuei67PhosphotyrosineBy similarity1
Modified residuei106Cysteine sulfinic acid (-SO2H); alternateBy similarity1
Lipidationi106S-palmitoyl cysteine; alternateBy similarity1
Cross-linki130Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei148N6-acetyllysineCombined sources1
Modified residuei182N6-succinyllysineCombined sources1

Post-translational modificationi

Sumoylated on Lys-130 by PIAS2 or PIAS4; which is essential for cell-growth promoting activity and transforming activity.By similarity
Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Lipoprotein, Oxidation, Palmitate, Phosphoprotein, Ubl conjugation, Zymogen

Proteomic databases

EPDiQ99LX0
MaxQBiQ99LX0
PaxDbiQ99LX0
PeptideAtlasiQ99LX0
PRIDEiQ99LX0
TopDownProteomicsiQ99LX0

2D gel databases

REPRODUCTION-2DPAGEQ99LX0
UCD-2DPAGEQ99LX0

PTM databases

iPTMnetiQ99LX0
PhosphoSitePlusiQ99LX0
SwissPalmiQ99LX0

Expressioni

Tissue specificityi

Expressed in erythroblasts and in mature red blood cells from peripheral blood (at protein level) (PubMed:20800516). In pancreas, expression is higher in islets than surrounding exocrine tissues (PubMed:22611253).2 Publications

Developmental stagei

Expression increases during erythroid development (at protein level) (PubMed:20800516). In pancreatic islets, expression increases during aging (PubMed:22611253).2 Publications

Inductioni

By hydrogen peroxide.1 Publication

Gene expression databases

BgeeiENSMUSG00000028964
ExpressionAtlasiQ99LX0 baseline and differential
GenevisibleiQ99LX0 MM

Interactioni

Subunit structurei

Homodimer. Binds EFCAB6/DJBP and PIAS2. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR. Binds to HIPK1 (By similarity). Interacts (via N-terminus) with OTUD7B (PubMed:21097510). Interacts with BBS1, CLCF1 and MTERF (PubMed:21097510). Interacts (via C-terminus) with NCF1; the interaction is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation (PubMed:26021615).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi208257, 18 interactors
IntActiQ99LX0, 11 interactors
MINTiQ99LX0
STRINGi10090.ENSMUSP00000030805

Structurei

3D structure databases

ProteinModelPortaliQ99LX0
SMRiQ99LX0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C56 family.Curated

Phylogenomic databases

eggNOGiKOG2764 Eukaryota
COG0693 LUCA
GeneTreeiENSGT00390000001231
HOGENOMiHOG000063194
HOVERGENiHBG053511
InParanoidiQ99LX0
KOiK05687
OMAiMMNGSHY
OrthoDBiEOG091G12NS
PhylomeDBiQ99LX0
TreeFamiTF300119

Family and domain databases

Gene3Di3.40.50.880, 1 hit
InterProiView protein in InterPro
IPR029062 Class_I_gatase-like
IPR006287 DJ-1
IPR002818 DJ-1/PfpI
PfamiView protein in Pfam
PF01965 DJ-1_PfpI, 1 hit
SUPFAMiSSF52317 SSF52317, 1 hit
TIGRFAMsiTIGR01383 not_thiJ, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99LX0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASKRALVIL AKGAEEMETV IPVDVMRRAG IKVTVAGLAG KDPVQCSRDV
60 70 80 90 100
MICPDTSLED AKTQGPYDVV VLPGGNLGAQ NLSESPMVKE ILKEQESRKG
110 120 130 140 150
LIAAICAGPT ALLAHEVGFG CKVTTHPLAK DKMMNGSHYS YSESRVEKDG
160 170 180
LILTSRGPGT SFEFALAIVE ALVGKDMANQ VKAPLVLKD
Length:189
Mass (Da):20,021
Last modified:June 1, 2001 - v1
Checksum:i877C825CCA07468F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti127P → T in BAE40278 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB015652 mRNA Translation: BAA29063.2
AK146368 mRNA Translation: BAE27118.1
AK153948 mRNA Translation: BAE32271.1
AK168341 mRNA Translation: BAE40278.1
AL607084 Genomic DNA No translation available.
BC002187 mRNA Translation: AAH02187.1
CCDSiCCDS18975.1
RefSeqiNP_065594.2, NM_020569.3
UniGeneiMm.277349

Genome annotation databases

EnsembliENSMUST00000030805; ENSMUSP00000030805; ENSMUSG00000028964
ENSMUST00000105673; ENSMUSP00000101298; ENSMUSG00000028964
ENSMUST00000105674; ENSMUSP00000101299; ENSMUSG00000028964
ENSMUST00000105675; ENSMUSP00000101300; ENSMUSG00000028964
GeneIDi57320
KEGGimmu:57320
UCSCiuc008vxz.2 mouse

Similar proteinsi

Entry informationi

Entry nameiPARK7_MOUSE
AccessioniPrimary (citable) accession number: Q99LX0
Secondary accession number(s): O88306, Q3THB9, Q3U509
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: June 1, 2001
Last modified: May 23, 2018
This is version 140 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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