PGH1_RAT
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 03-AUG-2022, entry version 170.
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 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. 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. {ECO:0000250|UniProtKB:P23219}.
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 -!- 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 GlyGen; Q63921; 4 sites.
DR jPOST; Q63921; -.
DR PaxDb; Q63921; -.
DR UCSC; RGD:3439; rat.
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; IDA:RGD.
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:0007568; P:aging; IEP:RGD.
DR GO; GO:0019371; P:cyclooxygenase pathway; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; IEA:InterPro.
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 GO; GO:0019233; P:sensory perception of pain; IMP:RGD.
DR Gene3D; 1.10.640.10; -; 1.
DR InterPro; IPR029580; COX-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:SF6; PTHR11903:SF6; 1.
DR Pfam; PF03098; An_peroxidase; 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 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
