| IED ID | IndEnz0017000026 |
| Enzyme Type ID | manganese peroxidase000026 |
| Protein Name |
Prostaglandin G/H synthase 2 EC 1.14.99.1 Cyclooxygenase-2 COX-2 PHS II Prostaglandin H2 synthase 2 PGH synthase 2 PGHS-2 Prostaglandin-endoperoxide synthase 2 |
| Gene Name | Ptgs2 Cox-2 Cox2 |
| 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 | MLFRAVLLCAALALSHAANPCCSNPCQNRGECMSIGFDQYKCDCTRTGFYGENCTTPEFLTRIKLLLKPTPNTVHYILTHFKGVWNIVNNIPFLRNSIMRYVLTSRSHLIDSPPTYNVHYGYKSWEAFSNLSYYTRALPPVADDCPTPMGVKGNKELPDSKEVLEKVLLRREFIPDPQGTNMMFAFFAQHFTHQFFKTDQKRGPGFTRGLGHGVDLNHVYGETLDRQHKLRLFQDGKLKYQVIGGEVYPPTVKDTQVDMIYPPHVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCDILKQEHPEWDDERLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNQQFQYQNRIASEFNTLYHWHPLLPDTFNIEDQEYTFKQFLYNNSILLEHGLAHFVESFTRQIAGRVAGGRNVPIAVQAVAKASIDQSREMKYQSLNEYRKRFSLKPYTSFEELTGEKEMAAELKALYHDIDAMELYPALLVEKPRPDAIFGETMVELGAPFSLKGLMGNPICSPQYWKPSTFGGEVGFRIINTASIQSLICNNVKGCPFASFNVQDPQPTKTATINASASHSRLDDINPTVLIKRRSTEL |
| Enzyme Length | 604 |
| Uniprot Accession Number | P35355 |
| Absorption | |
| Active Site | ACT_SITE 193; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; ACT_SITE 371; /note=For cyclooxygenase activity; /evidence=ECO:0000250|UniProtKB:Q05769 |
| Activity Regulation | |
| Binding Site | BINDING 106; /note=Substrate; /evidence=ECO:0000250|UniProtKB:Q05769; BINDING 341; /note=Substrate; /evidence=ECO:0000250|UniProtKB:Q05769 |
| 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:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23729; Evidence={ECO:0000250|UniProtKB:P35354}; 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:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42597; Evidence={ECO:0000250|UniProtKB:P35354}; 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:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42601; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + 2 O2 = prostaglandin G3; Xref=Rhea:RHEA:50444, ChEBI:CHEBI:15379, ChEBI:CHEBI:58562, ChEBI:CHEBI:133133; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50445; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=AH2 + prostaglandin G3 = A + H2O + prostaglandin H3; Xref=Rhea:RHEA:50448, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:133133, ChEBI:CHEBI:133134; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50449; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(8Z,11Z,14Z)-eicosatrienoate + 2 O2 = prostaglandin G1; Xref=Rhea:RHEA:50424, ChEBI:CHEBI:15379, ChEBI:CHEBI:71589, ChEBI:CHEBI:133084; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50425; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=AH2 + prostaglandin G1 = A + H2O + prostaglandin H1; Xref=Rhea:RHEA:50432, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:90793, ChEBI:CHEBI:133084; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50433; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphoethanolamine + 2 O2 = 2-(prostaglandin G2)-sn-glycero-3-phosphoethanolamine; Xref=Rhea:RHEA:54204, ChEBI:CHEBI:15379, ChEBI:CHEBI:76091, ChEBI:CHEBI:138098; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54205; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=2-(prostaglandin G2)-sn-glycero-3-phosphoethanolamine + AH2 = 2-(prostaglandin H2)-sn-glycero-3-phosphoethanolamine + A + H2O; Xref=Rhea:RHEA:54208, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:138098, ChEBI:CHEBI:138099; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54209; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + 2 O2 = 2-(prostaglandin G2)-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:54212, ChEBI:CHEBI:15379, ChEBI:CHEBI:76079, ChEBI:CHEBI:138100; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54213; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=2-(prostaglandin G2)-sn-glycero-3-phosphocholine + AH2 = 2-(prostaglandin H2)-sn-glycero-3-phosphocholine + A + H2O; Xref=Rhea:RHEA:54216, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:138100, ChEBI:CHEBI:138101; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54217; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + AH2 = (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + A + H2O; Xref=Rhea:RHEA:48856, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:57409, ChEBI:CHEBI:57446; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48857; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + AH2 + O2 = 2-[(15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-sn-glycero-3-phosphocholine + A + H2O; Xref=Rhea:RHEA:53684, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:76079, ChEBI:CHEBI:137584; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53685; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + AH2 + O2 = 2-[(15R)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-sn-glycero-3-phosphocholine + A + H2O; Xref=Rhea:RHEA:53680, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:76079, ChEBI:CHEBI:137583; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53681; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + AH2 + O2 = 2-[(11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoyl]-sn-glycero-3-phosphocholine + A + H2O; Xref=Rhea:RHEA:53676, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:76079, ChEBI:CHEBI:137582; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53677; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = 9-hydroxy-(10E,12Z)-octadecadienoate + A + H2O; Xref=Rhea:RHEA:50864, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:30245, ChEBI:CHEBI:133820; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50865; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = 13-hydroxy-(9Z,11E)-octadecadienoate + A + H2O; Xref=Rhea:RHEA:50860, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:30245, ChEBI:CHEBI:133819; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50861; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (15R)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + A + H2O; Xref=Rhea:RHEA:50856, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:32395, ChEBI:CHEBI:78837; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50857; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoate + A + H2O; Xref=Rhea:RHEA:50852, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:32395, ChEBI:CHEBI:78836; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50853; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (11R)-hydroxy-(5Z,8Z,12E,14Z,17Z)-eicosapentaenoate + A + H2O; Xref=Rhea:RHEA:50848, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562, ChEBI:CHEBI:90820; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50849; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (18S)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + A + H2O; Xref=Rhea:RHEA:50200, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562, ChEBI:CHEBI:132083; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50201; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (18R)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + A + H2O; Xref=Rhea:RHEA:48836, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562, ChEBI:CHEBI:90818; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48837; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (15R)-hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + A + H2O; Xref=Rhea:RHEA:48840, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562, ChEBI:CHEBI:90819; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48841; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (15S)-hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + A + H2O; Xref=Rhea:RHEA:50196, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562, ChEBI:CHEBI:132087; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50197; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(7Z,10Z,13Z,16Z,19Z)-docosapentaenoate + AH2 + O2 = 13R-hydroxy-(7Z,10Z,14E,16Z,19Z)-docosapentaenoate + A + H2O; Xref=Rhea:RHEA:48852, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:77224, ChEBI:CHEBI:90824; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48853; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + AH2 + O2 = 13-hydroxy-(4Z,7Z,10Z,14E,16Z,19Z)-docosahexaenoate + A + H2O; Xref=Rhea:RHEA:48820, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:77016, ChEBI:CHEBI:90815; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48821; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (5S,15R)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate + A + H2O; Xref=Rhea:RHEA:48812, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:90632, ChEBI:CHEBI:90812; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48813; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + AH2 + O2 = 17R-hydroxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate + A + H2O; Xref=Rhea:RHEA:48816, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:77016, ChEBI:CHEBI:90814; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48817; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate + A + H2O; Xref=Rhea:RHEA:48808, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:90632, ChEBI:CHEBI:90813; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48809; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (5S,11R)-dihydroxy-(6E,8Z,12E,14Z)-eicosatetraenoate + A + H2O; Xref=Rhea:RHEA:48804, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:90632, ChEBI:CHEBI:90810; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48805; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + 2 O2 = 2-glyceryl-prostaglandin G2; Xref=Rhea:RHEA:45288, ChEBI:CHEBI:15379, ChEBI:CHEBI:52392, ChEBI:CHEBI:85165; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45289; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=2-glyceryl-prostaglandin G2 + AH2 = 2-glyceryl-prostaglandin H2 + A + H2O; Xref=Rhea:RHEA:45292, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:85165, ChEBI:CHEBI:85166; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45293; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (15R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate; Xref=Rhea:RHEA:42284, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:82626; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42285; Evidence={ECO:0000250|UniProtKB:P35354}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 11R-hydroperoxy-(5Z,8Z,12E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:42280, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:82628; Evidence={ECO:0000250|UniProtKB:P35354};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42281; Evidence={ECO:0000250|UniProtKB:P35354}; |
| 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. Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins. In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids. Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response. Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols. Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation. Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2. In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection. In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity). {ECO:0000250|UniProtKB:P35354, ECO:0000250|UniProtKB:Q05769}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Lipid metabolism; prostaglandin biosynthesis. {ECO:0000250|UniProtKB:P35354}. |
| nucleotide Binding | |
| Features | Active site (2); Binding site (2); Chain (1); Disulfide bond (5); Domain (1); Glycosylation (4); Metal binding (1); Modified residue (2); Sequence conflict (18); Signal peptide (1); Site (1) |
| Keywords | Acetylation;Dioxygenase;Direct protein sequencing;Disulfide bond;Endoplasmic reticulum;Fatty acid biosynthesis;Fatty acid metabolism;Glycoprotein;Heme;Iron;Lipid biosynthesis;Lipid metabolism;Membrane;Metal-binding;Microsome;Nucleus;Oxidoreductase;Peroxidase;Prostaglandin biosynthesis;Prostaglandin metabolism;Reference proteome;S-nitrosylation;Signal |
| Interact With | |
| Induction | INDUCTION: By cytokines and mitogens. |
| Subcellular Location | SUBCELLULAR LOCATION: Microsome membrane {ECO:0000250|UniProtKB:P35354}; Peripheral membrane protein {ECO:0000250|UniProtKB:P35354}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P35354}; Peripheral membrane protein {ECO:0000250|UniProtKB:P35354}. Nucleus inner membrane {ECO:0000250|UniProtKB:P35354}; Peripheral membrane protein {ECO:0000250|UniProtKB:P35354}. Nucleus outer membrane {ECO:0000250|UniProtKB:P35354}; Peripheral membrane protein {ECO:0000250|UniProtKB:P35354}. Note=Detected on the lumenal side of the endoplasmic reticulum and nuclear envelope. {ECO:0000250|UniProtKB:P35354}. |
| Modified Residue | MOD_RES 526; /note=S-nitrosocysteine; /evidence=ECO:0000250|UniProtKB:P35354; MOD_RES 565; /note=O-acetylserine; /evidence=ECO:0000250|UniProtKB:Q05769 |
| Post Translational Modification | PTM: S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526. {ECO:0000250|UniProtKB:P35354}.; PTM: Acetylated at Ser-565 by SPHK1. During neuroinflammation, acetylation by SPHK1 promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia. {ECO:0000250|UniProtKB:Q05769}. |
| Signal Peptide | SIGNAL 1..17; /evidence=ECO:0000269|PubMed:1556140 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10229132; 11211925; 11756433; 12232777; 12535784; 12708469; 12916703; 14871450; 15464832; 15740981; 15775781; 16247333; 16467505; 16479074; 16781689; 16983392; 17112505; 17245358; 17272666; 17429720; 17485303; 17537981; 17543437; 17645304; 17660401; 17673547; 17673564; 17675820; 17699727; 17701021; 17704356; 17720896; 17766482; 17825173; 17827730; 17828456; 17876871; 17881518; 17883899; 18097056; 18266613; 18279516; 18310519; 18336855; 18348265; 18373278; 18383135; 18398660; 18435714; 18456673; 18462380; 18480553; 18481165; 18497304; 18519738; 18523723; 18540883; 18542928; 18554636; 18606213; 18637715; 18646190; 18657281; 18706904; 18758904; 18764909; 18769055; 18795192; 19180200; 19194550; 19567182; 19940926; 20051374; 20056215; 20141620; 20472710; 20602232; 20643531; 20950588; 21048090; 21051526; 21268133; 21273371; 21303331; 21311042; 21335517; 21362433; 21385433; 21394482; 21441310; 21521772; 21623034; 21641970; 21643627; 21678415; 21701788; 21718970; 21741371; 21763290; 21846384; 21866634; 21893983; 21944479; 21951301; 22165968; 22289897; 22306367; 22777528; 22902858; 23406865; 25193092; 25546515; 26514267; 29091898; 9630216; |
| Motif | |
| Gene Encoded By | |
| Mass | 69,164 |
| Kinetics | |
| Metal Binding | METAL 374; /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; RHEA:50444; RHEA:50445; RHEA:50448; RHEA:50449; RHEA:50424; RHEA:50425; RHEA:50432; RHEA:50433; RHEA:54204; RHEA:54205; RHEA:54208; RHEA:54209; RHEA:54212; RHEA:54213; RHEA:54216; RHEA:54217; RHEA:48856; RHEA:48857; RHEA:53684; RHEA:53685; RHEA:53680; RHEA:53681; RHEA:53676; RHEA:53677; RHEA:50864; RHEA:50865; RHEA:50860; RHEA:50861; RHEA:50856; RHEA:50857; RHEA:50852; RHEA:50853; RHEA:50848; RHEA:50849; RHEA:50200; RHEA:50201; RHEA:48836; RHEA:48837; RHEA:48840; RHEA:48841; RHEA:50196; RHEA:50197; RHEA:48852; RHEA:48853; RHEA:48820; RHEA:48821; RHEA:48812; RHEA:48813; RHEA:48816; RHEA:48817; RHEA:48808; RHEA:48809; RHEA:48804; RHEA:48805; RHEA:45288; RHEA:45289; RHEA:45292; RHEA:45293; RHEA:42284; RHEA:42285; RHEA:42280; RHEA:42281 |
| Cross Reference Brenda | 1.14.99.1; |