PGH2_BOVIN
ID PGH2_BOVIN Reviewed; 604 AA.
AC O62698; O46517; O62665;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 158.
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=COX2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11207216; DOI=10.1095/biolreprod64.3.983;
RA Liu J., Antaya M., Goff A.K., Boerboom D., Silversides D.W., Lussier J.G.,
RA Sirois J.;
RT "Molecular characterization of bovine prostaglandin G/H synthase-2 and
RT regulation in uterine stromal cells.";
RL Biol. Reprod. 64:983-991(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 105-253.
RX PubMed=9348208; DOI=10.1210/endo.138.11.5527;
RA Asselin E., Drolet P., Fortier M.A.;
RT "Cellular mechanisms involved during oxytocin-induced prostaglandin F2alpha
RT production in endometrial epithelial cells in vitro: role of
RT cyclooxygenase-2.";
RL Endocrinology 138:4798-4805(1997).
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. The
CC cyclooxygenase activity oxygenates arachidonate (AA, C20:4(n-6)) to the
CC hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase
CC activity reduces PGG2 to the hydroxy endoperoxide PGH2, the precursor
CC of all 2-series prostaglandins and thromboxanes. This complex
CC transformation is initiated by abstraction of hydrogen at carbon 13
CC (with S-stereochemistry), followed by insertion of molecular O2 to form
CC the 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) (By similarity). During neuroinflammation, plays a role in
CC neuronal secretion of specialized preresolving mediators (SPMs) 15R-
CC lipoxin A4 that regulates phagocytic microglia (By similarity).
CC {ECO:0000250|UniProtKB:P35354, 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 (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-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; AF031698; AAC04702.1; -; mRNA.
DR EMBL; AF031699; AAC28562.1; -; Genomic_DNA.
DR EMBL; AF004944; AAC05592.1; -; mRNA.
DR RefSeq; NP_776870.1; NM_174445.2.
DR AlphaFoldDB; O62698; -.
DR SMR; O62698; -.
DR STRING; 9913.ENSBTAP00000018774; -.
DR BindingDB; O62698; -.
DR ChEMBL; CHEMBL3331; -.
DR DrugCentral; O62698; -.
DR PeroxiBase; 3330; BtPGHS02.
DR PaxDb; O62698; -.
DR PRIDE; O62698; -.
DR GeneID; 282023; -.
DR KEGG; bta:282023; -.
DR CTD; 5743; -.
DR eggNOG; KOG2408; Eukaryota.
DR InParanoid; O62698; -.
DR OrthoDB; 324380at2759; -.
DR BRENDA; 1.14.99.1; 908.
DR UniPathway; UPA00662; -.
DR PRO; PR:O62698; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005637; C:nuclear inner membrane; ISS:UniProtKB.
DR GO; GO:0005640; C:nuclear outer membrane; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IBA:GO_Central.
DR GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR GO; GO:0004666; F:prostaglandin-endoperoxide synthase activity; ISS:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IMP:AgBase.
DR GO; GO:0019371; P:cyclooxygenase pathway; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR GO; GO:0000212; P:meiotic spindle organization; IMP:AgBase.
DR GO; GO:0001550; P:ovarian cumulus expansion; IMP:AgBase.
DR GO; GO:0040019; P:positive regulation of embryonic development; IMP:AgBase.
DR GO; GO:1904146; P:positive regulation of meiotic cell cycle process involved in oocyte maturation; IMP:AgBase.
DR GO; GO:1900195; P:positive regulation of oocyte maturation; IMP:AgBase.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:AgBase.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IMP:AgBase.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:InterPro.
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 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_0000023872"
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"
FT CONFLICT 6
FT /note="L -> M (in Ref. 1; AAC28562)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="E -> D (in Ref. 2; AAC05592)"
FT /evidence="ECO:0000305"
FT CONFLICT 458
FT /note="V -> L (in Ref. 1; AAC28562)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 604 AA; 69163 MW; 16EA2E51D0A01A45 CRC64;
MLARALLLCA AVALSGAANP CCSHPCQNRG VCMSVGFDQY KCDCTRTGFY GENCTTPEFL
TRIKLLLKPT PNTVHYILTH FKGVWNIVNK ISFLRNMIMR YVLTSRSHLI ESPPTYNVHY
SYKSWEAFSN LSYYTRALPP VPDDCPTPMG VKGRKELPDS KEVVKKVLLR RKFIPDPQGT
NLMFAFFAQH FTHQFFKTDF ERGPAFTKGK NHGVDLSHIY GESLERQHKL RLFKDGKMKY
QMINGEMYPP TVKDTQVEMI YPPHVPEHLK FAVGQEVFGL VPGLMMYATI WLREHNRVCD
VLKQEHPEWG DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE LLFNQQFQYQ
NRIAAEFNTL YHWHPLLPDV FQIDGQEYNY QQFIYNNSVL LEHGLTQFVE SFTRQRAGRV
AGGRNLPVAV EKVSKASIDQ SREMKYQSFN EYRKRFLVKP YESFEELTGE KEMAAELEAL
YGDIDAMEFY PALLVEKPRP DAIFGETMVE AGAPFSLKGL MGNPICSPEY WKPSTFGGEV
GFKIINTASI QSLICSNVKG CPFTSFSVQD THLTKTVTIN ASSSHSGLDD INPTVLLKER
STEL
