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UniProt functional annotation for Q05769 | ||
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| UniProt code: Q05769. |
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| Organism: | |
Mus musculus (Mouse). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus. |
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| 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 (PubMed:22942274, PubMed:12925531, PubMed:20463020, PubMed:20810665, PubMed:21489986). 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 (PubMed:22942274, PubMed:12925531, PubMed:20463020, PubMed:20810665, PubMed:21489986). 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 (By similarity). 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 (By similarity). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (By similarity). 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 (By similarity). 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 (By similarity). 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 (PubMed:29662056). {ECO:0000250|UniProtKB:P35354, ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:20810665, ECO:0000269|PubMed:21489986, ECO:0000269|PubMed:22942274, ECO:0000269|PubMed:29662056}. |
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| 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:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:20810665, ECO:0000269|PubMed:21489986, ECO:0000269|PubMed:22942274}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23729; Evidence={ECO:0000305|PubMed:12925531, ECO:0000305|PubMed:20463020, ECO:0000305|PubMed:20810665, ECO:0000305|PubMed:21489986, ECO:0000305|PubMed:22942274}; |
| 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:0000269|PubMed:12244105, ECO:0000269|PubMed:22942274}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42597; Evidence={ECO:0000305|PubMed:12244105, ECO:0000305|PubMed:22942274}; |
| 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:0000269|PubMed:12244105, ECO:0000269|PubMed:22942274}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42601; Evidence={ECO:0000305|PubMed:12244105, ECO:0000305|PubMed:22942274}; |
| 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:0000269|PubMed:12244105, ECO:0000269|PubMed:22942274}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45289; Evidence={ECO:0000305|PubMed:12244105, ECO:0000305|PubMed:22942274}; |
| 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:0000269|PubMed:12244105, ECO:0000269|PubMed:22942274}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45293; Evidence={ECO:0000305|PubMed:12244105, ECO:0000305|PubMed:22942274}; |
| 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}; |
| Cofactor: | |
Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:8967954}; Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit. {ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:8967954}; |
| Activity regulation: | |
Inhibited by the nonsteroidal anti-inflammatory drugs aspirin, naproxen, diclofenac, meclofenamic acid, indomethacin and their analogs. {ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20810665}. |
| Pathway: | |
Lipid metabolism; prostaglandin biosynthesis. {ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:20810665, ECO:0000269|PubMed:21489986}. |
| Subunit: | |
Homodimer. {ECO:0000269|PubMed:10811226, ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:21467029, ECO:0000269|PubMed:21489986, ECO:0000269|PubMed:8967954}. |
| Subcellular location: | |
Microsome membrane {ECO:0000269|PubMed:9545330}; Peripheral membrane protein. Endoplasmic reticulum membrane {ECO:0000269|PubMed:9545330}; Peripheral membrane protein. Nucleus inner membrane {ECO:0000305|PubMed:9545330}; Peripheral membrane protein. Nucleus outer membrane {ECO:0000305|PubMed:9545330}; Peripheral membrane protein. Note=Detected on the lumenal side of the endoplasmic reticulum and nuclear envelope. {ECO:0000250|UniProtKB:P35354}. |
| Tissue specificity: | |
Following colon injury, expressed in the wound bed mesenchyme during the first phase of repair, probably by colonic mesenchymal stem cells (at protein level). {ECO:0000269|PubMed:22465430}. |
| Developmental stage: | |
During colonic wound repair, highly up-regulated (more than 1600-fold) in the mesenchyme of the wound bed 2 days after injury as compared to uninjured mucosa. Further increase in expression is observed at day 4 following injury (close to 2200-fold). Down- regulated at day 6 (only 93-fold increase as compared to uninjured mucosa). {ECO:0000269|PubMed:22465430}. |
| Induction: | |
By cytokines and mitogens. {ECO:0000269|PubMed:1339449}. |
| 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:0000269|PubMed:29662056}. |
| Disruption phenotype: | |
Mutant mice exhibit defects in colonic mucosal wound repair. {ECO:0000269|PubMed:22465430}. |
| Miscellaneous: | |
The conversion of arachidonate to prostaglandin H2 is a 2 step reaction: a cyclooxygenase (COX) reaction which converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The nonsteroidal anti-inflammatory drugs (NSAIDs) binding site corresponds to the cyclooxygenase active site. |
| Miscellaneous: | |
Conversion of arachidonate to prostaglandin H2 is mediated by 2 different isozymes: the constitutive PTGS1 and the inducible PTGS2. PTGS1 is expressed constitutively and generally produces prostanoids acutely in response to hormonal stimuli to fine- tune physiological processes requiring instantaneous, continuous regulation (e.g. hemostasis). PTGS2 is inducible and typically produces prostanoids that mediate responses to physiological stresses such as infection and inflammation. |
| Miscellaneous: | |
PTGS1 and PTGS2 are the targets of nonsteroidal anti- inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is able to produce an irreversible inactivation of the enzyme through a serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. PTGS2 is the principal isozyme responsible for production of inflammatory prostaglandins. New generation PTGSs inhibitors strive to be selective for PTGS2, to avoid side effects such as gastrointestinal complications and ulceration. |
| Similarity: | |
Belongs to the prostaglandin G/H synthase family. {ECO:0000305}. |
Annotations taken from UniProtKB at the EBI.