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Protein

Protein/nucleic acid deglycase DJ-1

Gene

park7

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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. Also displays an apparent glyoxalase activity that in fact reflects its deglycase activity (By similarity). 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:17166173). It is involved in neuroprotective mechanisms as well as cell growth and transformation. Its involvement in protein repair could also explain other unrelated functions. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (By similarity).By similarity1 Publication

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

Keywordsi

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

Protein family/group databases

MEROPSiC56.971.

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-1zDJ-1By similarity
Short name:
zDJ-1
Gene namesi
Name:park7Imported
Synonyms:dj1Imported
ORF Names:zgc:103725
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Chromosome 11

Organism-specific databases

ZFINiZDB-GENE-041010-5. 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

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_0000405563? – 189Removed in mature form
ChainiPRO_00002859701 – ?Protein/nucleic acid deglycase DJ-1

Amino acid modifications

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

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

PaxDbiQ5XJ36.
PRIDEiQ5XJ36.

Expressioni

Tissue specificityi

Larval brain and gut from 96 hours post-fertilization (hpf). Ubiquitous in adult; most abundant in brain, eye, heart and muscle. Within brain, neuronal expression is widespread, particularly in the cerebellum, medullary reticular formation and diencephalon. Expressed in major forebrain and diencephalic dopaminergic cell groups.2 Publications

Developmental stagei

Present from tailbud stage (10 hpf) through to adult. Levels increase from 24-120 hpf.2 Publications

Gene expression databases

BgeeiENSDARG00000034826.
ExpressionAtlasiQ5XJ36. baseline.

Interactioni

Subunit structurei

Homodimer.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi7955.ENSDARP00000041530.

Structurei

3D structure databases

ProteinModelPortaliQ5XJ36.
SMRiQ5XJ36.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C56 family.Sequence analysis

Phylogenomic databases

eggNOGiKOG2764. Eukaryota.
COG0693. LUCA.
GeneTreeiENSGT00390000001231.
HOGENOMiHOG000063194.
HOVERGENiHBG053511.
InParanoidiQ5XJ36.
KOiK05687.
OMAiTCYPGFE.
OrthoDBiEOG091G12NS.
PhylomeDBiQ5XJ36.
TreeFamiTF300119.

Family and domain databases

Gene3Di3.40.50.880. 1 hit.
InterProiView protein in InterPro
IPR029062. Class_I_gatase-like.
IPR002818. DJ-1/PfpI.
IPR006287. DJ1.
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.

Q5XJ36-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGKRALVIL AKGAEEMETV IPVDVMRRAG IAVTVAGLAG KEPVQCSREV
60 70 80 90 100
MICPDSSLED AHKQGPYDVV LLPGGLLGAQ NLSESPAVKE VLKDQEGRKG
110 120 130 140 150
LIAAICAGPT ALLAHGIAYG STVTTHPGAK DKMMAGDHYK YSEARVQKDG
160 170 180
NVITSRGPGT SFEFALTIVE ELMGAEVAAQ VKAPLILKD
Length:189
Mass (Da):19,764
Last modified:November 23, 2004 - v1
Checksum:iF1C4F9F923FB2FF1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ882651 mRNA. Translation: ABI64158.1.
BC083475 mRNA. Translation: AAH83475.1.
RefSeqiNP_001005938.1. NM_001005938.1.
UniGeneiDr.85181.

Genome annotation databases

EnsembliENSDART00000041531; ENSDARP00000041530; ENSDARG00000034826.
GeneIDi449674.
KEGGidre:449674.

Similar proteinsi

Entry informationi

Entry nameiPARK7_DANRE
AccessioniPrimary (citable) accession number: Q5XJ36
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: November 23, 2004
Last modified: September 27, 2017
This is version 90 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Glyoxylase activity previously reported may reflect in fact its deglycase activity.By similarity
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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families