| IED ID | IndEnz0018001260 |
| Enzyme Type ID | peroxidase001260 |
| Protein Name |
Prostaglandin G/H synthase 1 EC 1.14.99.1 Cyclooxygenase-1 COX-1 Prostaglandin H2 synthase 1 PGH synthase 1 PGHS-1 PHS 1 Prostaglandin-endoperoxide synthase 1 |
| Gene Name | Ptgs1 Cox-1 Cox1 |
| 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 | MSRRSLSLQFPLLLLLLLLPPPPVLLTDAGVPSPVNPCCYYPCQNQGVCVRFGLDHYQCDCTRTGYSGPNCTIPEIWTWLRSSLRPSPSFTHFLLTHGYWIWEFVNATFIREVLMRLVITVRSNLIPSPPTYNTAHDYISWESFSNVSYYTRILPSVPKDCPTPMGTKGKKQLPDIHLLAQRLLLRREFIPGPQGTNVLFAFFAQHFTHQFFKTSGKMGPGFTKALGHGVDLGHIYGDSLERQYHLRLFKDGKLKYQVLDGEVYPPSVEQASVLMRYPPGVPPEKQMAVGQEVFGLLPGLMLFSTIWLREHNRVCDLLKEEHPTWDDEQLFQTTRLILIGETIKIIIEEYVQHLSGYFLQLKFDPELLFRAQFQYRNRIALEFNHLYHWHPLMPDSFQVGSQEYSYEQFLFNTSMLVDYGVEALVDAFSRQRAGRIGGGRNFDYHVLHVAEDVIKESREMRLQSFNEYRKRFGLKPYTSFQEFTGEKEMAAELEELYGDIDALEFYPGLMLEKCQPNSLFGESMIEMGAPFSLKGLLGNPICSPEYWKPSTFGGDVGFNIVNTASLKKLVCLNTKTCPYVSFRVPDYPGDDGSVFVRPSTEL |
| Enzyme Length | 602 |
| Uniprot Accession Number | Q63921 |
| Absorption | |
| Active Site | ACT_SITE 209; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; ACT_SITE 387; /note=For cyclooxygenase activity; /evidence=ECO:0000250 |
| Activity Regulation | ACTIVITY REGULATION: The cyclooxygenase activity is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen, flurbiprofen, ketoprofen, naproxen, flurbiprofen, anirolac, fenclofenac and diclofenac. {ECO:0000250|UniProtKB:P23219}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = A + H2O + prostaglandin H2; Xref=Rhea:RHEA:23728, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:32395, ChEBI:CHEBI:57405; EC=1.14.99.1; Evidence={ECO:0000250|UniProtKB:P23219};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23729; Evidence={ECO:0000250|UniProtKB:P23219}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = prostaglandin G2; Xref=Rhea:RHEA:42596, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:82629; Evidence={ECO:0000250|UniProtKB:P23219};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42597; Evidence={ECO:0000250|UniProtKB:P23219}; CATALYTIC ACTIVITY: Reaction=AH2 + prostaglandin G2 = A + H2O + prostaglandin H2; Xref=Rhea:RHEA:42600, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:57405, ChEBI:CHEBI:82629; Evidence={ECO:0000250|UniProtKB:P23219};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42601; Evidence={ECO:0000250|UniProtKB:P23219}; |
| DNA Binding | |
| EC Number | 1.14.99.1 |
| Enzyme Function | FUNCTION: Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate, with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates arachidonate (AA, C20:4(n-6)) to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide PGH2, the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells. {ECO:0000250|UniProtKB:P23219}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Lipid metabolism; prostaglandin biosynthesis. {ECO:0000250|UniProtKB:P23219}. |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Disulfide bond (5); Domain (1); Glycosylation (4); Metal binding (1); Sequence conflict (19); Signal peptide (1); Site (1) |
| Keywords | Dioxygenase;Disulfide bond;EGF-like domain;Endoplasmic reticulum;Fatty acid biosynthesis;Fatty acid metabolism;Glycoprotein;Heme;Iron;Lipid biosynthesis;Lipid metabolism;Membrane;Metal-binding;Microsome;Oxidoreductase;Peroxidase;Prostaglandin biosynthesis;Prostaglandin metabolism;Reference proteome;Signal |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Microsome membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | SIGNAL 1..26; /evidence=ECO:0000250 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10229132; 11063829; 11211925; 11565600; 11758166; 11849824; 11861778; 11882689; 11917005; 12020867; 12086957; 12160205; 12467530; 12657565; 12708469; 12811798; 12855310; 12888618; 12916703; 12971960; 14576556; 14600435; 14613912; 14684611; 15059644; 15207919; 15351851; 15550559; 15633603; 15644490; 15795519; 15935072; 16189289; 16323955; 16357083; 16569634; 16621493; 16781129; 16788145; 16949875; 16983392; 17184185; 17196338; 17245358; 17413918; 17429720; 17499644; 17537981; 17673564; 17699727; 17704356; 17766473; 17942724; 18292448; 18335410; 18349208; 18414395; 18456673; 18480553; 18584335; 18598693; 18637715; 19056763; 19060365; 19155631; 19444941; 19515980; 19625688; 19632905; 19658194; 19668263; 19696359; 19845835; 19912740; 19937640; 20549385; 20735829; 21362433; 21575628; 21667309; 21680698; 21701788; 22165968; 22219191; 22289897; 22436078; 23002358; 23090753; 23358504; 23362192; 23401543; 24014677; 24530741; 25216050; 25811420; 27178425; 28933223; 32909857; 34348138; |
| Motif | |
| Gene Encoded By | |
| Mass | 69,032 |
| Kinetics | |
| Metal Binding | METAL 390; /note=Iron (heme b axial ligand); /evidence=ECO:0000255|PROSITE-ProRule:PRU00298 |
| Rhea ID | RHEA:23728; RHEA:23729; RHEA:42596; RHEA:42597; RHEA:42600; RHEA:42601 |
| Cross Reference Brenda | 1.14.99.1; |