| IED ID | IndEnz0018000849 |
| Enzyme Type ID | peroxidase000849 |
| 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 COX2 |
| Organism | Equus caballus (Horse) |
| 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 Laurasiatheria Perissodactyla (odd-toed ungulates) Equidae (horses) Equus Equus Equus caballus (Horse) |
| Enzyme Sequence | MLARALLLCVALALGHAANPCCSNPCQNRGVCMSVGFDQYQCDCTRTGFYGENCSTPEFLTRIKLFLKPTPNTVHYILTHFKGVWNIVNSFPFLRNAVMKYVLVSRSHLIESPPTYNAQYGYKSWESFSNLSYYTRALPPVADGCPTPMGVKGKKELPDSKEIVEKFLLRRKFIPDPQGTNMMFAFFAQHFTHQFFKTDPKRGPAFTKGLGHGVDLSHIYGETLDRQHKLRLFKDGKMKYQIINGEVYPPTVKDTQVEMIYPPHIPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCDVLKQEHPEWDDERLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNQQFQYQNRIAAEFNTLYHWHPLLPDTFQIDDQEYNFQQFLYNNSILLEHGLTQFVESFSRQIAGRVAGGRNVPAAAQKIAKASIDQSREMKYQSLNEYRKRFRLTPYKSFEELTGEKEMAAELEALYGDIDAMELYPALLVEKPRPDAIFGETMVELGAPFSLKGLLGNPICSPDYWKPSTFGGEVGFKIINTASIQSLICNNVKGCPFTAFSVQDPQLSKAVTINASASHSGLDDVNPTVLLKERSTEL |
| Enzyme Length | 604 |
| Uniprot Accession Number | O19183 |
| 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). {ECO:0000250|UniProtKB:P35354}. |
| 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 (1); Signal peptide (1); Site (1) |
| Keywords | Dioxygenase;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 | |
| 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 |
| 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}. |
| Signal Peptide | SIGNAL 1..17; /evidence=ECO:0000250 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 17269882; 17609359; 17614138; 18584861; 18984785; 19443143; 19951126; 21529221; 22578628; 23122682; 23879794; |
| Motif | |
| Gene Encoded By | |
| Mass | 68,847 |
| 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 |