PGH1_BOVIN
ID PGH1_BOVIN Reviewed; 600 AA.
AC O62664; A7YWD4;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 164.
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; Synonyms=COX-1, COX1;
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 [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 121-379.
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. 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; BC134517; AAI34518.1; -; mRNA.
DR EMBL; AF004943; AAC05591.1; -; mRNA.
DR RefSeq; NP_001098793.1; NM_001105323.1.
DR AlphaFoldDB; O62664; -.
DR SMR; O62664; -.
DR STRING; 9913.ENSBTAP00000008833; -.
DR BindingDB; O62664; -.
DR ChEMBL; CHEMBL2860; -.
DR DrugCentral; O62664; -.
DR PeroxiBase; 3332; BtPGHS01.
DR PaxDb; O62664; -.
DR PRIDE; O62664; -.
DR GeneID; 282022; -.
DR KEGG; bta:282022; -.
DR CTD; 5742; -.
DR eggNOG; KOG2408; Eukaryota.
DR HOGENOM; CLU_022428_0_0_1; -.
DR InParanoid; O62664; -.
DR OrthoDB; 324380at2759; -.
DR TreeFam; TF329675; -.
DR BRENDA; 1.14.99.1; 908.
DR UniPathway; UPA00662; -.
DR PRO; PR:O62664; -.
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: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; IBA:GO_Central.
DR GO; GO:0019371; P:cyclooxygenase pathway; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:InterPro.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
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..24
FT /evidence="ECO:0000255"
FT CHAIN 25..600
FT /note="Prostaglandin G/H synthase 1"
FT /id="PRO_0000163113"
FT DOMAIN 32..70
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT ACT_SITE 207
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT ACT_SITE 385
FT /note="For cyclooxygenase activity"
FT /evidence="ECO:0000250"
FT BINDING 388
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 530
FT /note="Aspirin-acetylated serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 36..47
FT /evidence="ECO:0000250"
FT DISULFID 37..159
FT /evidence="ECO:0000250"
FT DISULFID 41..57
FT /evidence="ECO:0000250"
FT DISULFID 59..69
FT /evidence="ECO:0000250"
FT DISULFID 569..575
FT /evidence="ECO:0000250"
FT CONFLICT 229
FT /note="D -> G (in Ref. 2; AAC05591)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="Q -> R (in Ref. 2; AAC05591)"
FT /evidence="ECO:0000305"
FT CONFLICT 263
FT /note="P -> Q (in Ref. 2; AAC05591)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="H -> Q (in Ref. 2; AAC05591)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 600 AA; 68805 MW; 0B43E65DA9E2A2E9 CRC64;
MSRQGISLRF PLLLLLLSPS PVLPADPGAP APVNPCCYYP CQHQGICVRF GLDRYQCDCT
RTGYYGPNCT IPEIWTWLRT TLRPSPSFVH FLLTHGRWLW DFVNATFIRD KLMRLVLTVR
SNLIPSPPTY NVAHDYISWE SFSNVSYYTR ILPSVPRDCP TPMGTKGKKQ LPDAEFLSRR
FLLRRKFIPD PQGTNLMFAF FAQHFTHQFF KTSGKMGPGF TKALGHGVDL GHIYGDNLER
QYQLRLFKDG KLKYQMLNGE VYPPSVEEAP VLMHYPRGIP PQSQMAVGQE VFGLLPGLMV
YATIWLREHN RVCDLLKAEH PTWGDEQLFQ TARLILIGET IKIVIEEYVQ QLSGYFLQLK
FDPELLFGAQ FQYRNRIAME FNQLYHWHPL MPDSFRVGPQ DYSYEQFLFN TSMLVDYGVE
ALVDAFSRQP AGRIGGGRNI DHHILHVAVD VIKESRELRL QPFNEYRKRF GMKPYTSFQE
LTGEKEMAAE LEELYGDIDA LEFYPGLLLE KCHPNSIFGE SMIEMGAPFS LKGLLGNPIC
SPEYWKASTF GGDVGFNLVK TATLKKLVCL NTKTCPYVSF HVPDPHREDR PGVERPPTEL
