PGH2_SHEEP
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 03-AUG-2022, entry version 149.
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, 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, with a particular role in the inflammatory response
CC (PubMed:10438452). The cyclooxygenase activity oxygenates arachidonate
CC (AA, C20:4(n-6)) to the hydroperoxy endoperoxide prostaglandin G2
CC (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy
CC endoperoxide PGH2, the precursor of all 2-series prostaglandins and
CC thromboxanes (PubMed:10438452). 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 (By similarity). Similarly catalyzes successive
CC cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA,
CC C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding
CC PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (By
CC similarity). In an alternative pathway of prostanoid biosynthesis,
CC converts 2-arachidonoyl lysophopholipids to prostanoid
CC 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. Generates lipid mediators from n-
CC 3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type
CC mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces
CC them to corresponding alcohols (By similarity). Plays a role in the
CC generation of resolution phase interaction products (resolvins) during
CC both sterile and infectious inflammation. Metabolizes docosahexaenoate
CC (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins
CC (RvDs) (By similarity). As a component of the biosynthetic pathway of
CC E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3))
CC primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to
CC generate 18S-RvE1 and 18S-RvE2 (By similarity). In vascular endothelial
CC cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a
CC precursor for 13-series resolvins (RvTs) shown to activate macrophage
CC phagocytosis during bacterial infection (By similarity). In activated
CC leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates
CC (HETE) to 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). {ECO:0000250|UniProtKB:P35354,
CC ECO:0000250|UniProtKB:Q05769, ECO:0000269|PubMed:10438452}.
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 (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + 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 -!- 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 GeneID; 443460; -.
DR KEGG; oas:443460; -.
DR CTD; 5743; -.
DR eggNOG; KOG2408; Eukaryota.
DR OrthoDB; 324380at2759; -.
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:0006954; P:inflammatory response; IEA:InterPro.
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 Gene3D; 1.10.640.10; -; 1.
DR InterPro; IPR029576; COX-2.
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:SF8; PTHR11903:SF8; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF00008; EGF; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SUPFAM; SSF48113; SSF48113; 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
