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Protein

Protein DJ-1

Gene

PARK7

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease. 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. 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. 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. 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). In macrophages, interacts with the NADPH oxidase subunit NCF1to direct NADPH oxidase-dependent ROS production, and protects against sepsis (By similarity). Has been described as a protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and 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). However, another work ascribes the deglycation activity to a TRIS buffer artifact (By similarity).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

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 DJ-1
Short name:
DJ-1
Alternative name(s):
Parkinson disease protein 7 homolog
Protein deglycase DJ-1By similarity (EC:3.1.2.-By similarity, EC:3.5.1.124By similarity)
Gene namesi
Name:PARK7
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 16

Subcellular locationi

  • Cell membrane By similarity; Lipid-anchor By similarity
  • Cytoplasm By similarity
  • Nucleus By similarity
  • Membrane raft By similarity
  • Mitochondrion By similarity

  • Note: 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. Membrane raft localization in astrocytes and neuronal cells requires palmitoylation.By similarity

GO - Cellular componenti

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_0000405556? – 189Removed in mature form
Initiator methionineiRemovedBy similarity
ChainiPRO_00002524852 – ?Protein 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-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

PaxDbiQ5E946.
PeptideAtlasiQ5E946.
PRIDEiQ5E946.

Expressioni

Gene expression databases

BgeeiENSBTAG00000020518.

Interactioni

Subunit structurei

Homodimer. Binds EFCAB6/DJBP and PIAS2. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR. Interacts (via N-terminus) with OTUD7B. Interacts with BBS1, HIPK1, CLCF1 and MTERF. Forms a complex with PINK1 and PRKN (By similarity). Interacts (via C-terminus) with NCF1; the interaction is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000027339.

Structurei

3D structure databases

ProteinModelPortaliQ5E946.
SMRiQ5E946.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C56 family.Curated

Phylogenomic databases

eggNOGiKOG2764. Eukaryota.
COG0693. LUCA.
GeneTreeiENSGT00390000001231.
HOGENOMiHOG000063194.
HOVERGENiHBG053511.
InParanoidiQ5E946.
KOiK05687.
OMAiTCYPGFE.
OrthoDBiEOG091G12NS.
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.

Q5E946-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASKRALVIL AKGAEEMETV IPVDVMRRAG IKVTVAGLAG KDPVQCSRDV
60 70 80 90 100
VICPDASLED AKKEGPYDVV VLPGGNLGAQ NLSESAAVKE ILKEQEKRKG
110 120 130 140 150
LIAAICAGPT ALLAHEIGFG SKVTTHPLAK DKMMNGSHYS YSENRVEKDG
160 170 180
LILTSRGPGT SFEFALKIVE VLVGKEVADQ VKAPLVLKD
Length:189
Mass (Da):20,035
Last modified:March 15, 2005 - v1
Checksum:iC63FAA8D71056F2C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT021074 mRNA. Translation: AAX09091.1.
BC102707 mRNA. No translation available.
RefSeqiNP_001015572.1. NM_001015572.1.
XP_005217012.1. XM_005216955.3.
XP_005217013.1. XM_005216956.3.
UniGeneiBt.21745.

Genome annotation databases

EnsembliENSBTAT00000027339; ENSBTAP00000027339; ENSBTAG00000020518.
GeneIDi511268.
KEGGibta:511268.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiPARK7_BOVIN
AccessioniPrimary (citable) accession number: Q5E946
Secondary accession number(s): Q3ZC96
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: March 15, 2005
Last modified: June 7, 2017
This is version 93 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 deglycase function of this protein is not unanimous among researchers and is the subject of some controversy. The deglycation activity has been ascribed to a TRIS buffer artifact by a publication, however another work disputes these results.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