| IED ID | IndEnz0018001432 |
| Enzyme Type ID | peroxidase001432 |
| Protein Name |
Prostaglandin E synthase EC 5.3.99.3 Glutathione peroxidase PTGES EC 1.11.1.- Glutathione transferase PTGES EC 2.5.1.18 Microsomal glutathione S-transferase 1-like 1 MGST1-L1 Microsomal prostaglandin E synthase 1 MPGES-1 p53-induced gene 12 protein |
| Gene Name | PTGES MGST1L1 MPGES1 PGES PIG12 |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MPAHSLVMSSPALPAFLLCSTLLVIKMYVVAIITGQVRLRKKAFANPEDALRHGGPQYCRSDPDVERCLRAHRNDMETIYPFLFLGFVYSFLGPNPFVAWMHFLVFLVGRVAHTVAYLGKLRAPIRSVTYTLAQLPCASMALQILWEAARHL |
| Enzyme Length | 152 |
| Uniprot Accession Number | O14684 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Induced by interleukin IL1B. {ECO:0000269|PubMed:10760517}. |
| Binding Site | BINDING 38; /note="Glutathione"; /evidence="ECO:0000269|PubMed:18682561, ECO:0000269|PubMed:23431194, ECO:0007744|PDB:4AL0, ECO:0007744|PDB:4BPM, ECO:0007744|PDB:4WAB, ECO:0007744|PDB:4YK5, ECO:0007744|PDB:4YL0, ECO:0007744|PDB:4YL1, ECO:0007744|PDB:4YL3, ECO:0007744|PDB:5BQG, ECO:0007744|PDB:5BQH, ECO:0007744|PDB:5BQI, ECO:0007744|PDB:5K0I, ECO:0007744|PDB:5T36, ECO:0007744|PDB:5T37, ECO:0007744|PDB:5TL9"; BINDING 113; /note="Glutathione"; /evidence="ECO:0000269|PubMed:18682561, ECO:0000269|PubMed:23431194, ECO:0007744|PDB:4AL0, ECO:0007744|PDB:4BPM, ECO:0007744|PDB:4WAB, ECO:0007744|PDB:4YK5, ECO:0007744|PDB:4YL0, ECO:0007744|PDB:4YL1, ECO:0007744|PDB:4YL3, ECO:0007744|PDB:5BQG, ECO:0007744|PDB:5BQH, ECO:0007744|PDB:5BQI, ECO:0007744|PDB:5K0I, ECO:0007744|PDB:5T36, ECO:0007744|PDB:5T37, ECO:0007744|PDB:5TL9"; BINDING 117; /note="Glutathione"; /evidence="ECO:0000269|PubMed:18682561, ECO:0000269|PubMed:23431194, ECO:0007744|PDB:4AL0, ECO:0007744|PDB:4BPM, ECO:0007744|PDB:4WAB, ECO:0007744|PDB:4YK5, ECO:0007744|PDB:4YL0, ECO:0007744|PDB:4YL1, ECO:0007744|PDB:4YL3, ECO:0007744|PDB:5BQG, ECO:0007744|PDB:5BQH, ECO:0007744|PDB:5BQI, ECO:0007744|PDB:5K0I, ECO:0007744|PDB:5T36, ECO:0007744|PDB:5T37, ECO:0007744|PDB:5TL9" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=prostaglandin H2 = prostaglandin E2; Xref=Rhea:RHEA:12893, ChEBI:CHEBI:57405, ChEBI:CHEBI:606564; EC=5.3.99.3; Evidence={ECO:0000269|PubMed:10377395, ECO:0000269|PubMed:10869354, ECO:0000269|PubMed:12244105, ECO:0000269|PubMed:12460774, ECO:0000269|PubMed:12672824, ECO:0000269|PubMed:16439136, ECO:0000269|PubMed:18682561, ECO:0000269|PubMed:26755582, ECO:0000269|PubMed:27684486};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12894; Evidence={ECO:0000305|PubMed:10377395, ECO:0000305|PubMed:12460774, ECO:0000305|PubMed:12672824, ECO:0000305|PubMed:16439136}; CATALYTIC ACTIVITY: Reaction=2-glyceryl-prostaglandin H2 = 2-glyceryl-prostaglandin E2; Xref=Rhea:RHEA:53324, ChEBI:CHEBI:85166, ChEBI:CHEBI:137172; Evidence={ECO:0000269|PubMed:12244105};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53325; Evidence={ECO:0000305|PubMed:12244105}; CATALYTIC ACTIVITY: Reaction=prostaglandin G2 = (15S)-15-hydroperoxy-prostaglandin E2; Xref=Rhea:RHEA:64364, ChEBI:CHEBI:82629, ChEBI:CHEBI:152564; Evidence={ECO:0000269|PubMed:12672824};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64365; Evidence={ECO:0000305|PubMed:12672824}; CATALYTIC ACTIVITY: Reaction=1-chloro-2,4-dinitrobenzene + glutathione = 2,4-dinitrophenyl-S-glutathione + chloride + H(+); Xref=Rhea:RHEA:51220, ChEBI:CHEBI:15378, ChEBI:CHEBI:17996, ChEBI:CHEBI:34718, ChEBI:CHEBI:57925, ChEBI:CHEBI:133977; EC=2.5.1.18; Evidence={ECO:0000269|PubMed:12672824, ECO:0000269|PubMed:27684486};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51221; Evidence={ECO:0000305|PubMed:27684486}; CATALYTIC ACTIVITY: Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + 2 glutathione = (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:48620, ChEBI:CHEBI:15377, ChEBI:CHEBI:57450, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90632; Evidence={ECO:0000269|PubMed:12244105}; |
| DNA Binding | |
| EC Number | 5.3.99.3; 1.11.1.-; 2.5.1.18 |
| Enzyme Function | FUNCTION: Terminal enzyme of the cyclooxygenase (COX)-2-mediated prostaglandin E2 (PGE2) biosynthetic pathway. Catalyzes the glutathione-dependent oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) in response to inflammatory stimuli (PubMed:18682561, PubMed:10377395, PubMed:12672824, PubMed:12460774, PubMed:10869354, PubMed:12244105). Plays a key role in inflammation response, fever and pain (By similarity). Catalyzes also the oxidoreduction of endocannabinoids into prostaglandin glycerol esters and PGG2 into 15-hydroperoxy-PGE2 (PubMed:12244105, PubMed:12672824). In addition, displays low glutathione transferase and glutathione-dependent peroxidase activities, toward 1-chloro-2,4-dinitrobenzene and 5-hydroperoxyicosatetraenoic acid (5-HPETE), respectively (PubMed:12672824). {ECO:0000250|UniProtKB:Q9JM51, ECO:0000269|PubMed:10377395, ECO:0000269|PubMed:10869354, ECO:0000269|PubMed:12244105, ECO:0000269|PubMed:12460774, ECO:0000269|PubMed:12672824, ECO:0000269|PubMed:18682561}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Lipid metabolism; prostaglandin biosynthesis. {ECO:0000269|PubMed:10869354}. |
| nucleotide Binding | |
| Features | Beta strand (1); Binding site (3); Chain (1); Helix (7); Mutagenesis (21); Region (2); Sequence conflict (1); Site (2); Topological domain (4); Transmembrane (4) |
| Keywords | 3D-structure;Cytoplasm;Fatty acid biosynthesis;Fatty acid metabolism;Isomerase;Lipid biosynthesis;Lipid metabolism;Membrane;Oxidoreductase;Prostaglandin biosynthesis;Prostaglandin metabolism;Reference proteome;Transferase;Transmembrane;Transmembrane helix |
| Interact With | O15155; Q8WVX3-2; Q08426; Q8WWP7; Q96F15; Q04941; Q96IW7; Q8N6R1; Q9NRQ5; Q96HH6; Q9H0R3; Q6PI78; Q15836; O75379; O95292; O95070 |
| Induction | INDUCTION: Induced by the interleukin IL1B (PubMed:10377395, PubMed:10760517). Induced By p53/TP53 (PubMed:9305847). {ECO:0000269|PubMed:10377395, ECO:0000269|PubMed:10760517, ECO:0000269|PubMed:9305847}. |
| Subcellular Location | SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:10377395, ECO:0000269|PubMed:16439136, ECO:0000269|PubMed:18682561, ECO:0000269|PubMed:27684486}; Multi-pass membrane protein {ECO:0000303|PubMed:18682561}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:10869354}. Note=Colocalizes with PTGS1/COX-1 and PTGS2/COX-2 in the perinuclear compartment. {ECO:0000269|PubMed:10869354}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (16); Electron microscopy (1) |
| Cross Reference PDB | 3DWW; 4AL0; 4AL1; 4BPM; 4WAB; 4YK5; 4YL0; 4YL1; 4YL3; 5BQG; 5BQH; 5BQI; 5K0I; 5T36; 5T37; 5TL9; 6VL4; |
| Mapped Pubmed ID | 19124506; 19336370; 24803849; 25506719; 25961169; 26496610; 26653180; 27554445; 28190634; 33246032; |
| Motif | |
| Gene Encoded By | |
| Mass | 17,102 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=75 uM for glutathione {ECO:0000269|PubMed:12460774}; KM=160 uM for prostaglandin H2 (at 37 degrees) {ECO:0000269|PubMed:12672824}; KM=71 uM for glutathione (at 37 degrees) {ECO:0000269|PubMed:12672824}; KM=160 uM for prostaglandin G2 (at 37 degrees) {ECO:0000269|PubMed:12672824}; KM=14 uM for prostaglandin H2 {ECO:0000269|PubMed:12460774}; KM=130 uM for prostaglandin H2 {ECO:0000269|PubMed:16439136}; Vmax=170 umol/min/mg enzyme with prostaglandin H2 as substrate {ECO:0000269|PubMed:12672824}; Note=kcat is 50 sec(-1) for prostaglandin H2 as substrate (PubMed:12672824). kcat is 75 sec(-1) for prostaglandin H2 as substrate (PubMed:12672824). kcat is 21 sec(-1) for glutathione as substrate (PubMed:12672824). {ECO:0000269|PubMed:12672824}; |
| Metal Binding | |
| Rhea ID | RHEA:12893; RHEA:12894; RHEA:53324; RHEA:53325; RHEA:64364; RHEA:64365; RHEA:51220; RHEA:51221; RHEA:48620 |
| Cross Reference Brenda | 5.3.99.3; |