| IED ID | IndEnz0002009979 |
| Enzyme Type ID | protease009979 |
| Protein Name |
Parkinson disease protein 7 homolog Maillard deglycase Parkinsonism-associated deglycase Protein DJ-1zDJ-1 zDJ-1 Protein/nucleic acid deglycase DJ-1 EC 3.1.2.- EC 3.5.1.- EC 3.5.1.124 |
| Gene Name | park7 dj1 zgc:103725 |
| Organism | Danio rerio (Zebrafish) (Brachydanio rerio) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Actinopterygii Actinopteri Neopterygii Teleostei Osteoglossocephalai Clupeocephala Otomorpha Ostariophysi Otophysi Cypriniphysae Cypriniformes (carps and others) Cyprinoidei Danionidae Danioninae Danio Danio rerio (Zebrafish) (Brachydanio rerio) |
| Enzyme Sequence | MAGKRALVILAKGAEEMETVIPVDVMRRAGIAVTVAGLAGKEPVQCSREVMICPDSSLEDAHKQGPYDVVLLPGGLLGAQNLSESPAVKEVLKDQEGRKGLIAAICAGPTALLAHGIAYGSTVTTHPGAKDKMMAGDHYKYSEARVQKDGNVITSRGPGTSFEFALTIVEELMGAEVAAQVKAPLILKD |
| Enzyme Length | 189 |
| Uniprot Accession Number | Q5XJ36 |
| Absorption | |
| Active Site | ACT_SITE 106; /note=Nucleophile; /evidence=ECO:0000250|UniProtKB:Q99497; ACT_SITE 126; /evidence=ECO:0000250|UniProtKB:Q99497 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=H2O + N(omega)-(1-hydroxy-2-oxopropyl)-L-arginyl-[protein] = H(+) + L-arginyl-[protein] + lactate; Xref=Rhea:RHEA:49548, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:12428, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:24996, ChEBI:CHEBI:29965, ChEBI:CHEBI:131708; EC=3.5.1.124; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(6)-(1-hydroxy-2-oxopropyl)-L-lysyl-[protein] = H(+) + L-lysyl-[protein] + lactate; Xref=Rhea:RHEA:49552, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:12429, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:24996, ChEBI:CHEBI:29969, ChEBI:CHEBI:131709; EC=3.5.1.124; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + S-(1-hydroxy-2-oxopropyl)-L-cysteinyl-[protein] = H(+) + L-cysteinyl-[protein] + lactate; Xref=Rhea:RHEA:49556, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:12430, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:24996, ChEBI:CHEBI:29950, ChEBI:CHEBI:131710; EC=3.5.1.124; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(omega)-(1-hydroxy-2-oxoethyl)-L-arginyl-[protein] = glycolate + H(+) + L-arginyl-[protein]; Xref=Rhea:RHEA:57188, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:14844, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29805, ChEBI:CHEBI:29965, ChEBI:CHEBI:141553; EC=3.5.1.124; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(6)-(1-hydroxy-2-oxoethyl)-L-lysyl-[protein] = glycolate + H(+) + L-lysyl-[protein]; Xref=Rhea:RHEA:57192, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:14845, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29805, ChEBI:CHEBI:29969, ChEBI:CHEBI:141554; EC=3.5.1.124; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + S-(1-hydroxy-2-oxoethyl)-L-cysteinyl-[protein] = glycolate + H(+) + L-cysteinyl-[protein]; Xref=Rhea:RHEA:57196, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:14846, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29805, ChEBI:CHEBI:29950, ChEBI:CHEBI:141555; EC=3.5.1.124; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(2)-(1-hydroxy-2-oxopropyl)-dGTP = dGTP + H(+) + lactate; Xref=Rhea:RHEA:57244, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:24996, ChEBI:CHEBI:61429, ChEBI:CHEBI:141569; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(2)-(1-hydroxy-2-oxopropyl)-GTP = GTP + H(+) + lactate; Xref=Rhea:RHEA:57256, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:24996, ChEBI:CHEBI:37565, ChEBI:CHEBI:141570; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(2)-(1-hydroxy-2-oxopropyl)-GDP = GDP + H(+) + lactate; Xref=Rhea:RHEA:57260, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:24996, ChEBI:CHEBI:58189, ChEBI:CHEBI:141573; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(2)-(1-hydroxy-2-oxopropyl)-GMP = GMP + H(+) + lactate; Xref=Rhea:RHEA:57268, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:24996, ChEBI:CHEBI:58115, ChEBI:CHEBI:141575; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(2)-(1-hydroxy-2-oxoethyl)-dGTP = dGTP + glycolate + H(+); Xref=Rhea:RHEA:57248, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29805, ChEBI:CHEBI:61429, ChEBI:CHEBI:141572; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(2)-(1-hydroxy-2-oxoethyl)-GTP = glycolate + GTP + H(+); Xref=Rhea:RHEA:57252, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29805, ChEBI:CHEBI:37565, ChEBI:CHEBI:141571; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(2)-(1-hydroxy-2-oxoethyl)-GDP = GDP + glycolate + H(+); Xref=Rhea:RHEA:57264, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29805, ChEBI:CHEBI:58189, ChEBI:CHEBI:141574; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=H2O + N(2)-(1-hydroxy-2-oxoethyl)-GMP = glycolate + GMP + H(+); Xref=Rhea:RHEA:57304, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29805, ChEBI:CHEBI:58115, ChEBI:CHEBI:141576; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=an N(2)-(1-hydroxy-2-oxopropyl)-guanosine in RNA + H2O = a guanosine in RNA + H(+) + lactate; Xref=Rhea:RHEA:57288, Rhea:RHEA-COMP:14855, Rhea:RHEA-COMP:14858, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:24996, ChEBI:CHEBI:74269, ChEBI:CHEBI:141580; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=an N(2)-(1-hydroxy-2-oxopropyl)-2'-deoxyguanosine in DNA + H2O = a 2'-deoxyguanosine in DNA + H(+) + lactate; Xref=Rhea:RHEA:57300, Rhea:RHEA-COMP:11367, Rhea:RHEA-COMP:14856, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:24996, ChEBI:CHEBI:85445, ChEBI:CHEBI:141578; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=an N(2)-(1-hydroxy-2-oxoethyl)-guanosine in RNA + H2O = a guanosine in RNA + glycolate + H(+); Xref=Rhea:RHEA:57292, Rhea:RHEA-COMP:14855, Rhea:RHEA-COMP:14859, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29805, ChEBI:CHEBI:74269, ChEBI:CHEBI:141581; Evidence={ECO:0000250|UniProtKB:Q99497}; CATALYTIC ACTIVITY: Reaction=an N(2)-(1-hydroxy-2-oxoethyl)-2'-deoxyguanosine in DNA + H2O = a 2'-deoxyguanosine in DNA + glycolate + H(+); Xref=Rhea:RHEA:57296, Rhea:RHEA-COMP:11367, Rhea:RHEA-COMP:14857, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29805, ChEBI:CHEBI:85445, ChEBI:CHEBI:141579; Evidence={ECO:0000250|UniProtKB:Q99497}; |
| DNA Binding | |
| EC Number | 3.1.2.-; 3.5.1.-; 3.5.1.124 |
| Enzyme Function | FUNCTION: Multifunctional 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:17166173). 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. 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. But this function is rebuted by other works. 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. 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. Protects histones from adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin. Displays a very low glyoxalase activity that may reflect its deglycase activity. 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). {ECO:0000250|UniProtKB:Q99497, ECO:0000250|UniProtKB:Q99LX0, ECO:0000269|PubMed:17166173}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Cross-link (1); Lipidation (4); Modified residue (5); Propeptide (1) |
| Keywords | Acetylation;Autophagy;Cell membrane;Chaperone;Copper;Cytoplasm;Endoplasmic reticulum;Fertilization;Hydrolase;Inflammatory response;Isopeptide bond;Lipoprotein;Membrane;Mitochondrion;Nucleus;Oxidation;Palmitate;Phosphoprotein;Protease;RNA-binding;Reference proteome;Stress response;Tumor suppressor;Ubl conjugation;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O88767}; Lipid-anchor {ECO:0000250|UniProtKB:O88767}. Cytoplasm {ECO:0000250|UniProtKB:Q99497}. Nucleus {ECO:0000250|UniProtKB:Q99497}. Membrane raft {ECO:0000250|UniProtKB:O88767}. Mitochondrion {ECO:0000250|UniProtKB:Q99497}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q99497}. 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. Detected in tau inclusions in brains from neurodegenerative disease patients. Membrane raft localization in astrocytes and neuronal cells requires palmitoylation. {ECO:0000250|UniProtKB:Q99497}. |
| Modified Residue | MOD_RES 67; /note=Phosphotyrosine; /evidence=ECO:0000250|UniProtKB:Q99497; MOD_RES 106; /note=Cysteine sulfinic acid (-SO2H); /evidence=ECO:0000250|UniProtKB:Q99497; MOD_RES 106; /note=Cysteine sulfinic acid (-SO2H); alternate; /evidence=ECO:0000250|UniProtKB:Q99497; MOD_RES 148; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:Q99LX0; MOD_RES 182; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q99LX0 |
| Post Translational Modification | PTM: Sumoylated on Lys-130 by pias2 or pias4; which is essential for cell-growth promoting activity and transforming activity. {ECO:0000250|UniProtKB:Q99497}.; PTM: Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress. {ECO:0000250|UniProtKB:Q99497}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 19243613; 31218647; |
| Motif | |
| Gene Encoded By | |
| Mass | 19,764 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:49548; RHEA:49552; RHEA:49556; RHEA:57188; RHEA:57192; RHEA:57196; RHEA:57244; RHEA:57256; RHEA:57260; RHEA:57268; RHEA:57248; RHEA:57252; RHEA:57264; RHEA:57304; RHEA:57288; RHEA:57300; RHEA:57292; RHEA:57296 |
| Cross Reference Brenda |