ID   PGH1_RAT                Reviewed;         602 AA.
AC   Q63921; Q62731; Q63684;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-1998, sequence version 2.
DT   27-MAR-2024, entry version 177.
DE   RecName: Full=Prostaglandin G/H synthase 1 {ECO:0000305};
DE            EC=1.14.99.1 {ECO:0000250|UniProtKB:P23219};
DE   AltName: Full=Cyclooxygenase-1;
DE            Short=COX-1;
DE   AltName: Full=Prostaglandin H2 synthase 1;
DE            Short=PGH synthase 1;
DE            Short=PGHS-1;
DE            Short=PHS 1;
DE   AltName: Full=Prostaglandin-endoperoxide synthase 1;
DE   Flags: Precursor;
GN   Name=Ptgs1 {ECO:0000312|RGD:3439}; Synonyms=Cox-1, Cox1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley;
RX   PubMed=8274023; DOI=10.1006/abbi.1993.1601;
RA   Feng L., Sun W., Xia Y., Tang W.W., Chanmugam P., Soyoola E., Wilson C.B.,
RA   Hwang D.;
RT   "Cloning two isoforms of rat cyclooxygenase: differential regulation of
RT   their expression.";
RL   Arch. Biochem. Biophys. 307:361-368(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Fischer 344; TISSUE=Trachea;
RX   PubMed=7864644; DOI=10.1006/abbi.1995.1115;
RA   Kitzler J., Hill E., Hardman R., Reddy N., Philpot R., Eling T.E.;
RT   "Analysis and quantitation of splicing variants of the TPA-inducible PGHS-1
RT   mRNA in rat tracheal epithelial cells.";
RL   Arch. Biochem. Biophys. 316:856-863(1995).
RN   [3]
RP   REVIEW ON FUNCTION; TISSUE SPECIFICITY AND INHIBITION BY NSAIDS.
RX   PubMed=10966456; DOI=10.1146/annurev.biochem.69.1.145;
RA   Smith W.L., DeWitt D.L., Garavito R.M.;
RT   "Cyclooxygenases: structural, cellular, and molecular biology.";
RL   Annu. Rev. Biochem. 69:145-182(2000).
RN   [4]
RP   REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN COLORECTAL
RP   CANCER.
RX   PubMed=24605250; DOI=10.4292/wjgpt.v5.i1.40;
RA   Sostres C., Gargallo C.J., Lanas A.;
RT   "Aspirin, cyclooxygenase inhibition and colorectal cancer.";
RL   World J. Gastrointest. Pharmacol. Ther. 5:40-49(2014).
CC   -!- FUNCTION: Dual cyclooxygenase and peroxidase that plays an important
CC       role in the biosynthesis pathway of prostanoids, a class of C20
CC       oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-
CC       eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the
CC       inflammatory response. 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       This complex transformation is initiated by abstraction of hydrogen at
CC       carbon 13 (with S-stereochemistry), followed by insertion of molecular
CC       O2 to form 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. Involved in the constitutive production of
CC       prostanoids in particular in the stomach and platelets. In gastric
CC       epithelial cells, it is a key step in the generation of prostaglandins,
CC       such as prostaglandin E2 (PGE2), which plays an important role in
CC       cytoprotection. In platelets, it is involved in the generation of
CC       thromboxane A2 (TXA2), which promotes platelet activation and
CC       aggregation, vasoconstriction and proliferation of vascular smooth
CC       muscle cells. 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. {ECO:0000250|UniProtKB:P05979}.
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:P23219};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23729;
CC         Evidence={ECO:0000250|UniProtKB:P23219};
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:P23219};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42597;
CC         Evidence={ECO:0000250|UniProtKB:P23219};
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:P23219};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42601;
CC         Evidence={ECO:0000250|UniProtKB:P23219};
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:P05979};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75448;
CC         Evidence={ECO:0000250|UniProtKB:P05979};
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:P05979};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75460;
CC         Evidence={ECO:0000250|UniProtKB:P05979};
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:P05979};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75452;
CC         Evidence={ECO:0000250|UniProtKB:P05979};
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:P05979};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75456;
CC         Evidence={ECO:0000250|UniProtKB:P05979};
CC   -!- COFACTOR:
CC       Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000250};
CC       Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.
CC       {ECO:0000250};
CC   -!- ACTIVITY REGULATION: The cyclooxygenase activity is inhibited by
CC       nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen,
CC       flurbiprofen, ketoprofen, naproxen, flurbiprofen, anirolac, fenclofenac
CC       and diclofenac. {ECO:0000250|UniProtKB:P23219}.
CC   -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC       {ECO:0000250|UniProtKB:P23219}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Microsome membrane; Peripheral membrane protein.
CC       Endoplasmic reticulum membrane; Peripheral membrane protein.
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; U03388; AAA03465.1; -; mRNA.
DR   EMBL; S67721; AAB29400.2; -; mRNA.
DR   EMBL; U18060; AAA85823.1; -; mRNA.
DR   PIR; S39782; S39782.
DR   PIR; S69198; S69198.
DR   AlphaFoldDB; Q63921; -.
DR   SMR; Q63921; -.
DR   IntAct; Q63921; 1.
DR   STRING; 10116.ENSRNOP00000010218; -.
DR   BindingDB; Q63921; -.
DR   ChEMBL; CHEMBL4042; -.
DR   DrugCentral; Q63921; -.
DR   PeroxiBase; 3974; RnoPGHS01.
DR   GlyCosmos; Q63921; 4 sites, No reported glycans.
DR   GlyGen; Q63921; 4 sites.
DR   PhosphoSitePlus; Q63921; -.
DR   jPOST; Q63921; -.
DR   PaxDb; 10116-ENSRNOP00000010218; -.
DR   UCSC; RGD:3439; rat.
DR   AGR; RGD:3439; -.
DR   RGD; 3439; Ptgs1.
DR   eggNOG; KOG2408; Eukaryota.
DR   InParanoid; Q63921; -.
DR   PhylomeDB; Q63921; -.
DR   BRENDA; 1.14.99.1; 5301.
DR   Reactome; R-RNO-140180; COX reactions.
DR   Reactome; R-RNO-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR   UniPathway; UPA00662; -.
DR   PRO; PR:Q63921; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:UniProtKB.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0005635; C:nuclear envelope; IDA:RGD.
DR   GO; GO:0001750; C:photoreceptor outer segment; ISO:RGD.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
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; ISO:RGD.
DR   GO; GO:0019371; P:cyclooxygenase pathway; ISO:RGD.
DR   GO; GO:0007612; P:learning; IMP:RGD.
DR   GO; GO:0035633; P:maintenance of blood-brain barrier; IMP:RGD.
DR   GO; GO:0007613; P:memory; IMP:RGD.
DR   GO; GO:0032811; P:negative regulation of epinephrine secretion; IMP:RGD.
DR   GO; GO:0010700; P:negative regulation of norepinephrine secretion; IMP:RGD.
DR   GO; GO:0045987; P:positive regulation of smooth muscle contraction; IMP:RGD.
DR   GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR   GO; GO:0001516; P:prostaglandin biosynthetic process; IMP:RGD.
DR   GO; GO:0006693; P:prostaglandin metabolic process; ISO:RGD.
DR   GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB.
DR   GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR   GO; GO:0070542; P:response to fatty acid; IEP:RGD.
DR   GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
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:SF6; PROSTAGLANDIN G_H SYNTHASE 1; 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   Dioxygenase; Disulfide bond; EGF-like domain; Endoplasmic reticulum;
KW   Fatty acid biosynthesis; Fatty acid metabolism; Glycoprotein; Heme; Iron;
KW   Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding; Microsome;
KW   Oxidoreductase; Peroxidase; Prostaglandin biosynthesis;
KW   Prostaglandin metabolism; Reference proteome; Signal.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000250"
FT   CHAIN           27..602
FT                   /note="Prostaglandin G/H synthase 1"
FT                   /id="PRO_0000023870"
FT   DOMAIN          34..72
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   ACT_SITE        209
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT   ACT_SITE        387
FT                   /note="For cyclooxygenase activity"
FT                   /evidence="ECO:0000250"
FT   BINDING         390
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            532
FT                   /note="Aspirin-acetylated serine"
FT   CARBOHYD        70
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        106
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        146
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        412
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        38..49
FT                   /evidence="ECO:0000250"
FT   DISULFID        39..161
FT                   /evidence="ECO:0000250"
FT   DISULFID        43..59
FT                   /evidence="ECO:0000250"
FT   DISULFID        61..71
FT                   /evidence="ECO:0000250"
FT   DISULFID        571..577
FT                   /evidence="ECO:0000250"
FT   CONFLICT        36
FT                   /note="N -> I (in Ref. 1; AAA03465/AAB29400)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        116..117
FT                   /note="RL -> GW (in Ref. 1)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        119
FT                   /note="I -> L (in Ref. 1)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        192
FT                   /note="G -> A (in Ref. 1; AAA03465/AAB29400)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        263
FT                   /note="V -> L (in Ref. 1; AAA03465/AAB29400)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        274
FT                   /note="L -> K (in Ref. 1; AAA03465/AAB29400)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        290
FT                   /note="G -> A (in Ref. 1; AAA03465/AAB29400)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        339
FT                   /note="I -> R (in Ref. 1; AAB29400)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        344
FT                   /note="K -> E (in Ref. 1; AAA03465/AAB29400)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        381
FT                   /note="L -> M (in Ref. 1; AAA03465/AAB29400)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        392
FT                   /note="L -> F (in Ref. 1; AAA03465/AAB29400)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   602 AA;  69032 MW;  0BFAF7EBFDA0C7C2 CRC64;
     MSRRSLSLQF PLLLLLLLLP PPPVLLTDAG VPSPVNPCCY YPCQNQGVCV RFGLDHYQCD
     CTRTGYSGPN CTIPEIWTWL RSSLRPSPSF THFLLTHGYW IWEFVNATFI REVLMRLVIT
     VRSNLIPSPP TYNTAHDYIS WESFSNVSYY TRILPSVPKD CPTPMGTKGK KQLPDIHLLA
     QRLLLRREFI PGPQGTNVLF AFFAQHFTHQ FFKTSGKMGP GFTKALGHGV DLGHIYGDSL
     ERQYHLRLFK DGKLKYQVLD GEVYPPSVEQ ASVLMRYPPG VPPEKQMAVG QEVFGLLPGL
     MLFSTIWLRE HNRVCDLLKE EHPTWDDEQL FQTTRLILIG ETIKIIIEEY VQHLSGYFLQ
     LKFDPELLFR AQFQYRNRIA LEFNHLYHWH PLMPDSFQVG SQEYSYEQFL FNTSMLVDYG
     VEALVDAFSR QRAGRIGGGR NFDYHVLHVA EDVIKESREM RLQSFNEYRK RFGLKPYTSF
     QEFTGEKEMA AELEELYGDI DALEFYPGLM LEKCQPNSLF GESMIEMGAP FSLKGLLGNP
     ICSPEYWKPS TFGGDVGFNI VNTASLKKLV CLNTKTCPYV SFRVPDYPGD DGSVFVRPST
     EL
//