ID   PGH2_RABIT              Reviewed;         604 AA.
AC   O02768;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   27-MAR-2024, entry version 166.
DE   RecName: Full=Prostaglandin G/H synthase 2;
DE            EC=1.14.99.1;
DE   AltName: Full=Cyclooxygenase-2;
DE            Short=COX-2;
DE   AltName: Full=PHS II;
DE   AltName: Full=Prostaglandin H2 synthase 2;
DE            Short=PGH synthase 2;
DE            Short=PGHS-2;
DE   AltName: Full=Prostaglandin-endoperoxide synthase 2;
DE   Flags: Precursor;
GN   Name=PTGS2; Synonyms=COX-2, COX2;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=New Zealand white;
RX   PubMed=9249588; DOI=10.1152/ajprenal.1997.273.1.f18;
RA   Guan Y., Chang M., Cho W., Zhang Y., Redha R., Davis L., Chang S.,
RA   Dubois R.N., Hao C.M., Breyer M.;
RT   "Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal
RT   medullary interstitial cells.";
RL   Am. J. Physiol. 273:F18-F26(1997).
CC   -!- FUNCTION: Dual cyclooxygenase and peroxidase in the biosynthesis
CC       pathway of prostanoids, a class of C20 oxylipins mainly derived from
CC       arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with
CC       a particular role in the inflammatory response. The cyclooxygenase
CC       activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2
CC       (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy
CC       endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series
CC       prostaglandins and thromboxanes. This complex transformation is
CC       initiated by abstraction of hydrogen at carbon 13 (with S-
CC       stereochemistry), followed by insertion of molecular O2 to form the
CC       endoperoxide bridge between carbon 9 and 11 that defines
CC       prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase
CC       activity) yields a hydroperoxy group in PGG2 that is then reduced to
CC       PGH2 by two electrons. Similarly catalyzes successive cyclooxygenation
CC       and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and
CC       eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the
CC       precursors of 1- and 3-series prostaglandins. In an alternative pathway
CC       of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to
CC       prostanoid lysophopholipids, which are then hydrolyzed by intracellular
CC       phospholipases to release free prostanoids. Metabolizes 2-arachidonoyl
CC       glycerol yielding the glyceryl ester of PGH2, a process that can
CC       contribute to pain response. Generates lipid mediators from n-3 and n-6
CC       polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism.
CC       Oxygenates PUFAs to hydroperoxy compounds and then reduces them to
CC       corresponding alcohols. Plays a role in the generation of resolution
CC       phase interaction products (resolvins) during both sterile and
CC       infectious inflammation. Metabolizes docosahexaenoate (DHA, C22:6(n-3))
CC       to 17R-HDHA, a precursor of the D-series resolvins (RvDs). As a
CC       component of the biosynthetic pathway of E-series resolvins (RvEs),
CC       converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that
CC       is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-
CC       RvE2. In vascular endothelial cells, converts docosapentaenoate (DPA,
CC       C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs)
CC       shown to activate macrophage phagocytosis during bacterial infection.
CC       In activated leukocytes, contributes to oxygenation of
CC       hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-
CC       diHETE). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate,
CC       C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs)
CC       in a regio- and stereospecific manner,being (9R)-HODE ((9R)-hydroxy-
CC       (10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-
CC       octadecadienoate) its major products (By similarity). During
CC       neuroinflammation, plays a role in neuronal secretion of specialized
CC       preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic
CC       microglia (By similarity). {ECO:0000250|UniProtKB:P35354,
CC       ECO:0000250|UniProtKB:P79208, ECO:0000250|UniProtKB:Q05769}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = A + H2O +
CC         prostaglandin H2; Xref=Rhea:RHEA:23728, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:32395, ChEBI:CHEBI:57405; EC=1.14.99.1;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23729;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = prostaglandin G2;
CC         Xref=Rhea:RHEA:42596, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395,
CC         ChEBI:CHEBI:82629; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42597;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=AH2 + prostaglandin G2 = A + H2O + prostaglandin H2;
CC         Xref=Rhea:RHEA:42600, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:57405, ChEBI:CHEBI:82629;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42601;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + 2 O2 = prostaglandin
CC         G3; Xref=Rhea:RHEA:50444, ChEBI:CHEBI:15379, ChEBI:CHEBI:58562,
CC         ChEBI:CHEBI:133133; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50445;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=AH2 + prostaglandin G3 = A + H2O + prostaglandin H3;
CC         Xref=Rhea:RHEA:50448, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:133133, ChEBI:CHEBI:133134;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50449;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(8Z,11Z,14Z)-eicosatrienoate + 2 O2 = prostaglandin G1;
CC         Xref=Rhea:RHEA:50424, ChEBI:CHEBI:15379, ChEBI:CHEBI:71589,
CC         ChEBI:CHEBI:133084; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50425;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=AH2 + prostaglandin G1 = A + H2O + prostaglandin H1;
CC         Xref=Rhea:RHEA:50432, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:90793, ChEBI:CHEBI:133084;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50433;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-
CC         phosphoethanolamine + 2 O2 = 2-(prostaglandin G2)-sn-glycero-3-
CC         phosphoethanolamine; Xref=Rhea:RHEA:54204, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:76091, ChEBI:CHEBI:138098;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54205;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(prostaglandin G2)-sn-glycero-3-phosphoethanolamine + AH2 =
CC         2-(prostaglandin H2)-sn-glycero-3-phosphoethanolamine + A + H2O;
CC         Xref=Rhea:RHEA:54208, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:138098, ChEBI:CHEBI:138099;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54209;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine
CC         + 2 O2 = 2-(prostaglandin G2)-sn-glycero-3-phosphocholine;
CC         Xref=Rhea:RHEA:54212, ChEBI:CHEBI:15379, ChEBI:CHEBI:76079,
CC         ChEBI:CHEBI:138100; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54213;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(prostaglandin G2)-sn-glycero-3-phosphocholine + AH2 = 2-
CC         (prostaglandin H2)-sn-glycero-3-phosphocholine + A + H2O;
CC         Xref=Rhea:RHEA:54216, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:138100, ChEBI:CHEBI:138101;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54217;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + AH2 =
CC         (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + A + H2O;
CC         Xref=Rhea:RHEA:48856, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:57409, ChEBI:CHEBI:57446;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48857;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine
CC         + AH2 + O2 = 2-[(15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-sn-
CC         glycero-3-phosphocholine + A + H2O; Xref=Rhea:RHEA:53684,
CC         ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:76079, ChEBI:CHEBI:137584;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53685;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine
CC         + AH2 + O2 = 2-[(15R)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-sn-
CC         glycero-3-phosphocholine + A + H2O; Xref=Rhea:RHEA:53680,
CC         ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:76079, ChEBI:CHEBI:137583;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53681;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine
CC         + AH2 + O2 = 2-[(11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoyl]-sn-
CC         glycero-3-phosphocholine + A + H2O; Xref=Rhea:RHEA:53676,
CC         ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:76079, ChEBI:CHEBI:137582;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53677;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = 9-hydroxy-(10E,12Z)-
CC         octadecadienoate + A + H2O; Xref=Rhea:RHEA:50864, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:30245, ChEBI:CHEBI:133820;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50865;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = 13-hydroxy-(9Z,11E)-
CC         octadecadienoate + A + H2O; Xref=Rhea:RHEA:50860, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:30245, ChEBI:CHEBI:133819;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50861;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (15R)-hydroxy-
CC         (5Z,8Z,11Z,13E)-eicosatetraenoate + A + H2O; Xref=Rhea:RHEA:50856,
CC         ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:32395, ChEBI:CHEBI:78837;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50857;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (11R)-hydroxy-
CC         (5Z,8Z,12E,14Z)-eicosatetraenoate + A + H2O; Xref=Rhea:RHEA:50852,
CC         ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:17499, ChEBI:CHEBI:32395, ChEBI:CHEBI:78836;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50853;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (11R)-
CC         hydroxy-(5Z,8Z,12E,14Z,17Z)-eicosapentaenoate + A + H2O;
CC         Xref=Rhea:RHEA:50848, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562,
CC         ChEBI:CHEBI:90820; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50849;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (18S)-
CC         hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + A + H2O;
CC         Xref=Rhea:RHEA:50200, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562,
CC         ChEBI:CHEBI:132083; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50201;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (18R)-
CC         hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + A + H2O;
CC         Xref=Rhea:RHEA:48836, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562,
CC         ChEBI:CHEBI:90818; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48837;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (15R)-
CC         hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + A + H2O;
CC         Xref=Rhea:RHEA:48840, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562,
CC         ChEBI:CHEBI:90819; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48841;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (15S)-
CC         hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + A + H2O;
CC         Xref=Rhea:RHEA:50196, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:58562,
CC         ChEBI:CHEBI:132087; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50197;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(7Z,10Z,13Z,16Z,19Z)-docosapentaenoate + AH2 + O2 = 13R-
CC         hydroxy-(7Z,10Z,14E,16Z,19Z)-docosapentaenoate + A + H2O;
CC         Xref=Rhea:RHEA:48852, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:77224,
CC         ChEBI:CHEBI:90824; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48853;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + AH2 + O2 = 13-
CC         hydroxy-(4Z,7Z,10Z,14E,16Z,19Z)-docosahexaenoate + A + H2O;
CC         Xref=Rhea:RHEA:48820, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:77016,
CC         ChEBI:CHEBI:90815; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48821;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 =
CC         (5S,15R)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate + A + H2O;
CC         Xref=Rhea:RHEA:48812, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:90632,
CC         ChEBI:CHEBI:90812; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48813;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + AH2 + O2 = 17R-
CC         hydroxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate + A + H2O;
CC         Xref=Rhea:RHEA:48816, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:77016,
CC         ChEBI:CHEBI:90814; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48817;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 =
CC         (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate + A + H2O;
CC         Xref=Rhea:RHEA:48808, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:90632,
CC         ChEBI:CHEBI:90813; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48809;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 =
CC         (5S,11R)-dihydroxy-(6E,8Z,12E,14Z)-eicosatetraenoate + A + H2O;
CC         Xref=Rhea:RHEA:48804, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:90632,
CC         ChEBI:CHEBI:90810; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48805;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + 2 O2 = 2-
CC         glyceryl-prostaglandin G2; Xref=Rhea:RHEA:45288, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:52392, ChEBI:CHEBI:85165;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45289;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-glyceryl-prostaglandin G2 + AH2 = 2-glyceryl-prostaglandin
CC         H2 + A + H2O; Xref=Rhea:RHEA:45292, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:85165,
CC         ChEBI:CHEBI:85166; Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45293;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (15R)-hydroperoxy-
CC         (5Z,8Z,11Z,13E)-eicosatetraenoate; Xref=Rhea:RHEA:42284,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:82626;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42285;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 11R-hydroperoxy-
CC         (5Z,8Z,12E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:42280,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:82628;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42281;
CC         Evidence={ECO:0000250|UniProtKB:P35354};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = (9R)-hydroxy-(10E,12Z)-
CC         octadecadienoate + A + H2O; Xref=Rhea:RHEA:75447, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:30245, ChEBI:CHEBI:77895;
CC         Evidence={ECO:0000250|UniProtKB:P79208};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75448;
CC         Evidence={ECO:0000250|UniProtKB:P79208};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = (9S)-hydroxy-(10E,12Z)-
CC         octadecadienoate + A + H2O; Xref=Rhea:RHEA:75459, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:30245, ChEBI:CHEBI:77852;
CC         Evidence={ECO:0000250|UniProtKB:P79208};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75460;
CC         Evidence={ECO:0000250|UniProtKB:P79208};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = (13S)-hydroxy-(9Z,11E)-
CC         octadecadienoate + A + H2O; Xref=Rhea:RHEA:75451, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:30245, ChEBI:CHEBI:90850;
CC         Evidence={ECO:0000250|UniProtKB:P79208};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75452;
CC         Evidence={ECO:0000250|UniProtKB:P79208};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(9Z,12Z)-octadecadienoate + AH2 + O2 = (13R)-hydroxy-(9Z,11E)-
CC         octadecadienoate + A + H2O; Xref=Rhea:RHEA:75455, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:30245, ChEBI:CHEBI:136655;
CC         Evidence={ECO:0000250|UniProtKB:P79208};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75456;
CC         Evidence={ECO:0000250|UniProtKB:P79208};
CC   -!- COFACTOR:
CC       Name=heme b; Xref=ChEBI:CHEBI:60344;
CC         Evidence={ECO:0000250|UniProtKB:Q05769};
CC       Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.
CC       {ECO:0000250|UniProtKB:Q05769};
CC   -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC       {ECO:0000250|UniProtKB:P35354}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q05769}.
CC   -!- SUBCELLULAR LOCATION: Microsome membrane
CC       {ECO:0000250|UniProtKB:P35354}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P35354}. Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P35354}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P35354}. Nucleus inner membrane
CC       {ECO:0000250|UniProtKB:P35354}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P35354}. Nucleus outer membrane
CC       {ECO:0000250|UniProtKB:P35354}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P35354}. Note=Detected on the lumenal side of
CC       the endoplasmic reticulum and nuclear envelope.
CC       {ECO:0000250|UniProtKB:P35354}.
CC   -!- TISSUE SPECIFICITY: Highest expression in kidney and urinary bladder.
CC   -!- PTM: S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-
CC       nitrosylation may take place on different Cys residues in addition to
CC       Cys-526. {ECO:0000250|UniProtKB:P35354}.
CC   -!- PTM: Acetylated at Ser-565 by SPHK1. During neuroinflammation,
CC       acetylation by SPHK1 promotes neuronal secretion of specialized
CC       preresolving mediators (SPMs), especially 15-R-lipoxin A4, which
CC       results in an increase of phagocytic microglia.
CC       {ECO:0000250|UniProtKB:Q05769}.
CC   -!- MISCELLANEOUS: The conversion of arachidonate to prostaglandin H2 is a
CC       2 step reaction: a cyclooxygenase (COX) reaction which converts
CC       arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in
CC       which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase
CC       reaction occurs in a hydrophobic channel in the core of the enzyme. The
CC       peroxidase reaction occurs at a heme-containing active site located
CC       near the protein surface. The nonsteroidal anti-inflammatory drugs
CC       (NSAIDs) binding site corresponds to the cyclooxygenase active site.
CC   -!- MISCELLANEOUS: Conversion of arachidonate to prostaglandin H2 is
CC       mediated by 2 different isozymes: the constitutive PTGS1 and the
CC       inducible PTGS2. PTGS1 is expressed constitutively and generally
CC       produces prostanoids acutely in response to hormonal stimuli to fine-
CC       tune physiological processes requiring instantaneous, continuous
CC       regulation (e.g. hemostasis). PTGS2 is inducible and typically produces
CC       prostanoids that mediate responses to physiological stresses such as
CC       infection and inflammation.
CC   -!- MISCELLANEOUS: PTGS1 and PTGS2 are the targets of nonsteroidal anti-
CC       inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is
CC       able to produce an irreversible inactivation of the enzyme through a
CC       serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces
CC       inflammation, pain, and fever, and long-term use of these drugs reduces
CC       fatal thrombotic events, as well as the development of colon cancer and
CC       Alzheimer's disease. PTGS2 is the principal isozyme responsible for
CC       production of inflammatory prostaglandins. New generation PTGSs
CC       inhibitors strive to be selective for PTGS2, to avoid side effects such
CC       as gastrointestinal complications and ulceration.
CC   -!- SIMILARITY: Belongs to the prostaglandin G/H synthase family.
CC       {ECO:0000305}.
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DR   EMBL; U97696; AAB71222.1; -; mRNA.
DR   RefSeq; NP_001075857.1; NM_001082388.1.
DR   AlphaFoldDB; O02768; -.
DR   SMR; O02768; -.
DR   STRING; 9986.ENSOCUP00000014415; -.
DR   BindingDB; O02768; -.
DR   ChEMBL; CHEMBL1293198; -.
DR   DrugCentral; O02768; -.
DR   PeroxiBase; 4130; OcuPGHS02.
DR   GlyCosmos; O02768; 4 sites, No reported glycans.
DR   PaxDb; 9986-ENSOCUP00000014415; -.
DR   Ensembl; ENSOCUT00000016770.2; ENSOCUP00000014415.2; ENSOCUG00000016771.4.
DR   GeneID; 100009248; -.
DR   KEGG; ocu:100009248; -.
DR   CTD; 5743; -.
DR   eggNOG; KOG2408; Eukaryota.
DR   GeneTree; ENSGT00390000010743; -.
DR   InParanoid; O02768; -.
DR   OMA; NVHYGYK; -.
DR   OrthoDB; 1086441at2759; -.
DR   TreeFam; TF329675; -.
DR   UniPathway; UPA00662; -.
DR   Proteomes; UP000001811; Chromosome 16.
DR   Bgee; ENSOCUG00000016771; Expressed in ovary and 14 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR   GO; GO:0005637; C:nuclear inner membrane; ISS:UniProtKB.
DR   GO; GO:0005640; C:nuclear outer membrane; ISS:UniProtKB.
DR   GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR   GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0004666; F:prostaglandin-endoperoxide synthase activity; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR   GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl.
DR   GO; GO:0071498; P:cellular response to fluid shear stress; IEA:Ensembl.
DR   GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR   GO; GO:0071471; P:cellular response to non-ionic osmotic stress; IEA:Ensembl.
DR   GO; GO:0019371; P:cyclooxygenase pathway; ISS:UniProtKB.
DR   GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR   GO; GO:0007566; P:embryo implantation; IEA:Ensembl.
DR   GO; GO:1902219; P:negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress; IEA:Ensembl.
DR   GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IEA:Ensembl.
DR   GO; GO:0031622; P:positive regulation of fever generation; IEA:Ensembl.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR   GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; IEA:Ensembl.
DR   GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0032310; P:prostaglandin secretion; IEA:Ensembl.
DR   GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR   GO; GO:0150077; P:regulation of neuroinflammatory response; ISS:UniProtKB.
DR   GO; GO:0009624; P:response to nematode; IEA:Ensembl.
DR   GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR   CDD; cd00054; EGF_CA; 1.
DR   CDD; cd09816; prostaglandin_endoperoxide_synthase; 1.
DR   Gene3D; 1.10.640.10; Haem peroxidase domain superfamily, animal type; 1.
DR   Gene3D; 2.10.25.10; Laminin; 1.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR019791; Haem_peroxidase_animal.
DR   InterPro; IPR010255; Haem_peroxidase_sf.
DR   InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR   PANTHER; PTHR11903; PROSTAGLANDIN G/H SYNTHASE; 1.
DR   PANTHER; PTHR11903:SF8; PROSTAGLANDIN G_H SYNTHASE 2; 1.
DR   Pfam; PF03098; An_peroxidase; 1.
DR   PRINTS; PR00457; ANPEROXIDASE.
DR   SUPFAM; SSF57196; EGF/Laminin; 1.
DR   SUPFAM; SSF48113; Heme-dependent peroxidases; 1.
DR   PROSITE; PS50026; EGF_3; 1.
DR   PROSITE; PS50292; PEROXIDASE_3; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Dioxygenase; Disulfide bond; Endoplasmic reticulum;
KW   Fatty acid biosynthesis; Fatty acid metabolism; Glycoprotein; Heme; Iron;
KW   Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding; Microsome;
KW   Nucleus; Oxidoreductase; Peroxidase; Prostaglandin biosynthesis;
KW   Prostaglandin metabolism; Reference proteome; S-nitrosylation; Signal.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000250"
FT   CHAIN           18..604
FT                   /note="Prostaglandin G/H synthase 2"
FT                   /id="PRO_0000023878"
FT   DOMAIN          18..55
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   ACT_SITE        193
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   ACT_SITE        371
FT                   /note="For cyclooxygenase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   BINDING         106
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   BINDING         341
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   BINDING         374
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   SITE            516
FT                   /note="Aspirin-acetylated serine"
FT                   /evidence="ECO:0000250|UniProtKB:P35354"
FT   MOD_RES         526
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P35354"
FT   MOD_RES         565
FT                   /note="O-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   CARBOHYD        53
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        130
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        396
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        580
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        21..32
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   DISULFID        22..145
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   DISULFID        26..42
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   DISULFID        44..54
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   DISULFID        555..561
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
SQ   SEQUENCE   604 AA;  69007 MW;  C52F9F5BC1F493D7 CRC64;
     MLARALLLCA AVALSHAANP CCSNPCQNRG VCMTMGFDQY KCDCTRTGFY GENCSTPEFL
     TRIKLLLKPT PDTVHYILTH FKGVWNIVNS IPFLRNSIMK YVLTSRSHMI DSPPTYNVHY
     NYKSWEAFSN LSYYTRALPP VADDCPTPMG VKGKKELPDS KDVVEKLLLR RKFIPDPQGT
     NMMFAFFAQH FTHQFFKTDL KRGPAFTKGL GHGVDLNHIY GETLDRQHKL RLFKDGKMKY
     QVIDGEVYPP TVKDTQVEMI YPPHIPAHLQ FAVGQEVFGL VPGLMMYATI WLREHNRVCD
     VLKQEHPEWD DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE LLFNQQFQYQ
     NRIAAEFNTL YHWHPLLPDT FQIDDQQYNY QQFLYNNSIL LEHGLTQFVE SFTRQIAGRV
     AGGRNVPPAV QKVAKASIDQ SRQMKYQSLN EYRKRFLLKP YESFEELTGE KEMAAELEAL
     YGDIDAVELY PALLVERPRP DAIFGESMVE MGAPFSLKGL MGNPICSPNY WKPSTFGGEV
     GFKIVNTASI QSLICNNVKG CPFTSFNVPD PQLTKTVTIN ASASHSRLED INPTVLLKGR
     STEL
//