ID   PGH2_SHEEP              Reviewed;         603 AA.
AC   P79208;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   27-MAR-2024, entry version 155.
DE   RecName: Full=Prostaglandin G/H synthase 2;
DE            EC=1.14.99.1 {ECO:0000269|PubMed:10438452};
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=COX2;
OS   Ovis aries (Sheep).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Caprinae; Ovis.
OX   NCBI_TaxID=9940;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8878543; DOI=10.1006/bbrc.1996.1536;
RA   Zhang V., O'Sullivan M., Hussain H., Roswit W.T., Holtzman M.J.;
RT   "Molecular cloning, functional expression, and selective regulation of
RT   ovine prostaglandin H synthase-2.";
RL   Biochem. Biophys. Res. Commun. 227:499-506(1996).
RN   [2]
RP   PROTEIN SEQUENCE OF 17-52; 99-115; 183-196; 247-257; 286-306; 444-454;
RP   473-485 AND 508-532.
RC   TISSUE=Placenta;
RX   PubMed=7503555; DOI=10.1006/abbi.1995.9934;
RA   Johnson J.L., Wimsatt J., Buckel S.D., Dyer R.D., Maddipati K.R.;
RT   "Purification and characterization of prostaglandin H synthase-2 from sheep
RT   placental cotyledons.";
RL   Arch. Biochem. Biophys. 324:26-34(1995).
RN   [3]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=9448728; DOI=10.1006/abbi.1997.0443;
RA   Hamberg M.;
RT   "Stereochemistry of oxygenation of linoleic acid catalyzed by
RT   prostaglandin-endoperoxide H synthase-2.";
RL   Arch. Biochem. Biophys. 349:376-380(1998).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, AND INHIBITION BY NSAIDS.
RX   PubMed=10438452; DOI=10.1074/jbc.274.33.22903;
RA   Marnett L.J., Rowlinson S.W., Goodwin D.C., Kalgutkar A.S., Lanzo C.A.;
RT   "Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis
RT   and inhibition.";
RL   J. Biol. Chem. 274:22903-22906(1999).
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 (PubMed:9448728,
CC       PubMed:10438452). The cyclooxygenase activity oxygenates AA to the
CC       hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase
CC       activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2
CC       (PGH2), the precursor of all 2-series prostaglandins and thromboxanes
CC       (PubMed:10438452). This complex transformation is initiated by
CC       abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed
CC       by insertion of molecular O2 to form the endoperoxide bridge between
CC       carbon 9 and 11 that defines prostaglandins. The insertion of a second
CC       molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in
CC       PGG2 that is then reduced to PGH2 by two electrons (By similarity).
CC       Similarly catalyzes successive cyclooxygenation and peroxidation of
CC       dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA,
CC       C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-
CC       series prostaglandins (By similarity). In an alternative pathway of
CC       prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to
CC       prostanoid lysophopholipids, which are then hydrolyzed by intracellular
CC       phospholipases to release free prostanoids (By similarity). Metabolizes
CC       2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process
CC       that can contribute to pain response (By similarity). Plays a role in
CC       the generation of resolution phase interaction products (resolvins)
CC       during both sterile and infectious inflammation (By similarity).
CC       Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor
CC       of the D-series resolvins (RvDs) (By similarity). As a component of the
CC       biosynthetic pathway of E-series resolvins (RvEs), converts
CC       eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is
CC       further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-
CC       RvE2 (By similarity). In vascular endothelial cells, converts
CC       docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-
CC       series resolvins (RvTs) shown to activate macrophage phagocytosis
CC       during bacterial infection (By similarity). In activated leukocytes,
CC       contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to
CC       diHETES (5,15-diHETE and 5,11-diHETE) (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). Can also use linoleate (LA, (9Z,12Z)-
CC       octadecadienoate, C18:2(n-6)) as substrate and produce
CC       hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner,
CC       being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-
CC       HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products
CC       (PubMed:9448728). {ECO:0000250|UniProtKB:P35354,
CC       ECO:0000250|UniProtKB:Q05769, ECO:0000269|PubMed:10438452,
CC       ECO:0000269|PubMed:9448728}.
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:0000269|PubMed:10438452};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23729;
CC         Evidence={ECO:0000305|PubMed:10438452};
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:0000269|PubMed:10438452};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42597;
CC         Evidence={ECO:0000305|PubMed:10438452};
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:0000269|PubMed:10438452};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42601;
CC         Evidence={ECO:0000305|PubMed:10438452};
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:0000269|PubMed:9448728};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50865;
CC         Evidence={ECO:0000305|PubMed:9448728};
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:0000269|PubMed:9448728};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75448;
CC         Evidence={ECO:0000305|PubMed:9448728};
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:0000269|PubMed:9448728};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75460;
CC         Evidence={ECO:0000305|PubMed:9448728};
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:0000269|PubMed:9448728};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75452;
CC         Evidence={ECO:0000305|PubMed:9448728};
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:0000269|PubMed:9448728};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75456;
CC         Evidence={ECO:0000305|PubMed:9448728};
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   -!- 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   -!- PTM: S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-
CC       nitrosylation may take place on different Cys residues in addition to
CC       Cys-525. {ECO:0000250|UniProtKB:P35354}.
CC   -!- PTM: Acetylated at Ser-564 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; U68486; AAC48684.1; -; mRNA.
DR   PIR; JC5063; JC5063.
DR   RefSeq; NP_001009432.1; NM_001009432.1.
DR   AlphaFoldDB; P79208; -.
DR   SMR; P79208; -.
DR   STRING; 9940.ENSOARP00000008147; -.
DR   BindingDB; P79208; -.
DR   ChEMBL; CHEMBL4102; -.
DR   DrugCentral; P79208; -.
DR   PeroxiBase; 4122; OarPGHS02.
DR   GlyCosmos; P79208; 4 sites, No reported glycans.
DR   PaxDb; 9940-ENSOARP00000008147; -.
DR   GeneID; 443460; -.
DR   KEGG; oas:443460; -.
DR   CTD; 5743; -.
DR   eggNOG; KOG2408; Eukaryota.
DR   OrthoDB; 1086441at2759; -.
DR   BRENDA; 1.14.99.1; 2668.
DR   SABIO-RK; P79208; -.
DR   UniPathway; UPA00662; -.
DR   PRO; PR:P79208; -.
DR   Proteomes; UP000002356; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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: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:0019371; P:cyclooxygenase pathway; ISS:UniProtKB.
DR   GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB.
DR   GO; GO:0150077; P:regulation of neuroinflammatory response; ISS:UniProtKB.
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   1: Evidence at protein level;
KW   Acetylation; Dioxygenase; Direct protein sequencing; Disulfide bond;
KW   Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW   Glycoprotein; Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane;
KW   Metal-binding; Microsome; Nucleus; Oxidoreductase; Peroxidase;
KW   Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW   S-nitrosylation; Signal.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000269|PubMed:7503555"
FT   CHAIN           17..603
FT                   /note="Prostaglandin G/H synthase 2"
FT                   /id="PRO_0000023880"
FT   DOMAIN          17..54
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   ACT_SITE        192
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   ACT_SITE        370
FT                   /note="For cyclooxygenase activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   BINDING         105
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   BINDING         340
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   BINDING         373
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            515
FT                   /note="Aspirin-acetylated serine"
FT                   /evidence="ECO:0000250|UniProtKB:P35354"
FT   MOD_RES         525
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P35354"
FT   MOD_RES         564
FT                   /note="O-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   CARBOHYD        52
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        579
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        20..31
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   DISULFID        21..144
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   DISULFID        25..41
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   DISULFID        43..53
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   DISULFID        554..560
FT                   /evidence="ECO:0000250|UniProtKB:Q05769"
FT   CONFLICT        99..101
FT                   /note="RYV -> GYK (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        252
FT                   /note="K -> KH (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        256
FT                   /note="V -> N (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        520
FT                   /note="Missing (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        528
FT                   /note="E -> A (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   603 AA;  68969 MW;  E27F5E0549BB1C52 CRC64;
     MLARALLLCA AVVCGAANPC CSHPCQNRGV CMSVGFDQYK CDCTRTGFYG ENCTTPEFLT
     RIKLLLKPTP DTVHYILTHF KGVWNIVNKI SFLRNMIMRY VLTSRSHLIE SPPTYNVHYS
     YKSWEAFSNL SYYTRALPPV PDDCPTPMGV KGRKELPDSK EVVKKVLLRR KFIPDPQGTN
     LMFAFFAQHF THQFFKTDIE RGPAFTKGKN HGVDLSHVYG ESLERQHNRR LFKDGKMKYQ
     MINGEMYPPT VKDTQVEMIY PPHIPEHLKF AVGQEVFGLV PGLMMYATIW LREHNRVCDV
     LKQEHPEWGD EQLFQTSRLI LIGETIKIVI EDYVQHLSGY HFKLKFDPEL LFNQQFQYQN
     RIAAEFNTLY HWHPLLPDVF QIDGQEYNYQ QFIYNNSVLL EHGVTQFVES FTRQIAGRVA
     GRRNLPAAVE KVSKASLDQS REMKYQSFNE YRKRFLLKPY ESFEELTGEK EMAAELEALY
     GDIDAMELYP ALLVEKPAPD AIFGETMVEA GAPFSLKGLM GNPICSPEYW KPSTFGGEVG
     FKIINTASIQ SLICSNVKGC PFTSFSVQDA HLTKTVTINA SSSHSGLDDI NPTVLLKERS
     TEL
//