| IED ID | IndEnz0002006468 |
| Enzyme Type ID | protease006468 |
| Protein Name |
Parkinson disease protein 7 homolog Contraception-associated protein 1 Protein CAP1 Fertility protein SP22 Maillard deglycase Parkinsonism-associated deglycase Protein DJ-1 DJ-1 Protein/nucleic acid deglycase DJ-1 EC 3.1.2.- EC 3.5.1.- EC 3.5.1.124 |
| Gene Name | Park7 Cap1 |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MASKRALVILAKGAEEMETVIPVDIMRRAGIKVTVAGLAGKDPVQCSRDVVICPDTSLEEAKTQGPYDVVVLPGGNLGAQNLSESALVKEILKEQENRKGLIAAICAGPTALLAHEVGFGCKVTSHPLAKDKMMNGSHYSYSESRVEKDGLILTSRGPGTSFEFALAIVEALSGKDMANQVKAPLVLKD |
| Enzyme Length | 189 |
| Uniprot Accession Number | O88767 |
| 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: 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. 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. 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. 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 (By similarity). In pancreatic islets, involved in the maintenance of mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in an age- and diet dependent manner. Protects pancreatic beta cells from cell death induced by inflammatory and cytotoxic setting (By similarity). 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 NCF1 to direct NADPH oxidase-dependent ROS production, and protects against sepsis (By similarity). {ECO:0000250|UniProtKB:Q99497, ECO:0000250|UniProtKB:Q99LX0}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Cross-link (1); Initiator methionine (1); Lipidation (3); Modified residue (5); Propeptide (1); Site (1) |
| Keywords | Acetylation;Autophagy;Cell membrane;Chaperone;Copper;Cytoplasm;Direct protein sequencing;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:Q99LX0}; Lipid-anchor {ECO:0000250|UniProtKB:Q99LX0}. Cytoplasm {ECO:0000269|PubMed:10022524}. Membrane raft {ECO:0000269|PubMed:23847046}. Nucleus {ECO:0000269|PubMed:10022524}. Mitochondrion {ECO:0000269|PubMed:31536960}. Endoplasmic reticulum {ECO:0000269|PubMed:31536960}. 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 (By similarity). Membrane raft localization in astrocytes and neuronal cells requires palmitoylation (PubMed:23847046). {ECO:0000250|UniProtKB:Q99497, ECO:0000269|PubMed:23847046}. |
| Modified Residue | MOD_RES 2; /note=N-acetylalanine; /evidence=ECO:0000250|UniProtKB:Q99497; MOD_RES 67; /note=Phosphotyrosine; /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 | 11780923; 15673657; 16047164; 16227205; 16246899; 16396496; 16854843; 17038803; 17599367; 17609507; 18003894; 18373560; 20698836; 21426932; 22041943; 22132160; 22613231; 22710069; 22878563; 24157858; 24303086; 24969022; 25037998; 25726699; 25788877; 25915512; 26081287; 26873851; 26913805; 27171370; 27430285; 28035392; 28941803; 29069575; 29109055; 29287203; 29431188; 29649621; 29791076; 30506316; 31034784; 31593688; 31734455; 31878239; 32051471; 32061171; 32151250; 32157145; |
| Motif | |
| Gene Encoded By | |
| Mass | 19,974 |
| 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 |