PGH1_CANLF
ID PGH1_CANLF Reviewed; 603 AA.
AC Q8HZR1; F1PBX3; Q8HZR0;
DT 14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT 14-MAY-2014, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Prostaglandin G/H synthase 1;
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=COX1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), ALTERNATIVE SPLICING,
RP GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain cortex;
RX PubMed=12242329; DOI=10.1073/pnas.162468699;
RA Chandrasekharan N.V., Dai H., Roos K.L., Evanson N.K., Tomsik J.,
RA Elton T.S., Simmons D.L.;
RT "COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other
RT analgesic/antipyretic drugs: cloning, structure, and expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13926-13931(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer;
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
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 {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000269|PubMed:12242329}. Endoplasmic reticulum
CC membrane {ECO:0000269|PubMed:12242329}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12242329}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=COX-1;
CC IsoId=Q8HZR1-1; Sequence=Displayed;
CC Name=2; Synonyms=COX-3;
CC IsoId=Q8HZR1-2; Sequence=VSP_054856;
CC Name=3; Synonyms=PCOX-1a;
CC IsoId=Q8HZR1-3; Sequence=VSP_054856, VSP_054857;
CC Name=4; Synonyms=PCOX-1b;
CC IsoId=Q8HZR1-4; Sequence=VSP_054857;
CC -!- TISSUE SPECIFICITY: Brain cortex. Isoform 2 is expressed in the
CC cerebral cortex and heart.
CC -!- PTM: N-glycosylated. N-linked glycosylation is necessary for enzymatic
CC activity. {ECO:0000269|PubMed:12242329}.
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 -!- MISCELLANEOUS: [Isoform 3]: No enzymatic activity. Membrane-bound.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the prostaglandin G/H synthase family.
CC {ECO:0000305}.
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DR EMBL; AF535138; AAN33049.1; -; mRNA.
DR EMBL; AF535139; AAN38739.1; -; mRNA.
DR EMBL; AAEX03006907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001003023.1; NM_001003023.2.
DR AlphaFoldDB; Q8HZR1; -.
DR SMR; Q8HZR1; -.
DR STRING; 9612.ENSCAFP00000030067; -.
DR BindingDB; Q8HZR1; -.
DR ChEMBL; CHEMBL4133; -.
DR DrugCentral; Q8HZR1; -.
DR PeroxiBase; 3362; CfaPGHS01.
DR PaxDb; Q8HZR1; -.
DR Ensembl; ENSCAFT00040004500; ENSCAFP00040003864; ENSCAFG00040002347. [Q8HZR1-2]
DR Ensembl; ENSCAFT00040004521; ENSCAFP00040003882; ENSCAFG00040002347. [Q8HZR1-1]
DR Ensembl; ENSCAFT00040004622; ENSCAFP00040003972; ENSCAFG00040002347. [Q8HZR1-3]
DR Ensembl; ENSCAFT00845024089; ENSCAFP00845018920; ENSCAFG00845013501. [Q8HZR1-1]
DR GeneID; 403544; -.
DR KEGG; cfa:403544; -.
DR CTD; 5742; -.
DR VEuPathDB; HostDB:ENSCAFG00845013501; -.
DR eggNOG; KOG2408; Eukaryota.
DR GeneTree; ENSGT00390000010743; -.
DR HOGENOM; CLU_022428_0_0_1; -.
DR OMA; YNTSMLM; -.
DR OrthoDB; 324380at2759; -.
DR TreeFam; TF329675; -.
DR Reactome; R-CFA-140180; COX reactions.
DR Reactome; R-CFA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR UniPathway; UPA00662; -.
DR Proteomes; UP000002254; Chromosome 9.
DR Bgee; ENSCAFG00000020263; Expressed in spinal cord and 49 other tissues.
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 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 Alternative splicing; Dioxygenase; Disulfide bond; EGF-like domain;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Glycoprotein; Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Oxidoreductase; Peroxidase;
KW Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..603
FT /note="Prostaglandin G/H synthase 1"
FT /id="PRO_0000429170"
FT DOMAIN 35..73
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT ACT_SITE 210
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT ACT_SITE 388
FT /note="For cyclooxygenase activity"
FT /evidence="ECO:0000250"
FT BINDING 391
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 533
FT /note="Aspirin-acetylated serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 39..50
FT /evidence="ECO:0000250"
FT DISULFID 40..162
FT /evidence="ECO:0000250"
FT DISULFID 44..60
FT /evidence="ECO:0000250"
FT DISULFID 62..72
FT /evidence="ECO:0000250"
FT DISULFID 572..578
FT /evidence="ECO:0000250"
FT VAR_SEQ 3
FT /note="R -> REFDPEAPRNPLRLPGEPRMPGPALTSRSAG (in isoform 2
FT and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12242329"
FT /id="VSP_054856"
FT VAR_SEQ 122..340
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:12242329"
FT /id="VSP_054857"
FT CONFLICT 597
FT /note="E -> Q (in Ref. 1; AAN33049/AAN38739)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 603 AA; 69305 MW; 435B3E3A3D5DCCA6 CRC64;
MSRGSRLHRW PLLLLLLLLL PPPPVLPAEA RTPAPVNPCC YYPCQHQGIC VRFGLDRYQC
DCTRTGYSGP NCTIPELWTW LRNSLRPSPS FLHFLLTHGR WFWEFINATF IRDMLMRLVL
TARSNLIPSP PTYNIAHDYI SWESFSNVSY YTRVLPSVPQ DCPTPMGTKG KKQLPDAQLL
GRRFLLRRKF IPDPQGTNLM FAFFAQHFTH QFFKTSGKMG PGFTKALGHG VDLGHIYGDN
LDRQYQLRLF KDGKLKYQVL DGEMYPPSVE EAPVLMHYPR GILPQSQMAV GQEVFGLLPG
LMLYATLWLR EHNRVCDLLK AEHPTWGDEQ LFQTARLILI GETIKIVIEE YVQQLSGYFL
QLKFDPELLF SAQFQYRNRI AMEFNQLYHW HPLMPDSFWV GSQEYSYEQF LFNTSMLTHY
GIEALVDAFS RQSAGRIGGG RNIDHHVLHV AVETIKESRE LRLQPFNEYR KRFGMRPYMS
FQELTGEKEM AAELEELYGD IDALEFYPGL LLEKCHPNSI FGESMIEIGA PFSLKGLLGN
PICSPEYWKP STFGGEMGFN MVKTATLKKL VCLNTKTCPY VSFRVPDPHQ DGGPGVERPS
TEL
