PGH2_CHICK
ID PGH2_CHICK Reviewed; 603 AA.
AC P27607;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 163.
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=Mitogen-inducible PGHS;
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=CEF-147;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1849272; DOI=10.1073/pnas.88.7.2692;
RA Xie W., Chipman J.G., Robertson D.L., Erikson R.L., Simmons D.L.;
RT "Expression of a mitogen-responsive gene encoding prostaglandin synthase is
RT regulated by mRNA splicing.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:2692-2696(1991).
CC -!- FUNCTION: Converts arachidonate to prostaglandin H2 (PGH2), a committed
CC step in prostanoid synthesis. Constitutively expressed in some tissues
CC in physiological conditions, such as the endothelium, kidney and brain,
CC and in pathological conditions, such as in cancer. PTGS2 is responsible
CC for production of inflammatory prostaglandins. Up-regulation of PTGS2
CC is also associated with increased cell adhesion, phenotypic changes,
CC resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2
CC is a key step in the production of prostaglandin E2 (PGE2), which plays
CC important roles in modulating motility, proliferation and resistance to
CC apoptosis. {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:Q05769};
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; Peripheral membrane protein.
CC Endoplasmic reticulum membrane; Peripheral membrane protein.
CC -!- INDUCTION: By cytokines and mitogens.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M64990; AAA49050.1; -; mRNA.
DR PIR; A38630; A38630.
DR RefSeq; NP_001161190.1; NM_001167718.1.
DR RefSeq; NP_001161191.1; NM_001167719.1.
DR AlphaFoldDB; P27607; -.
DR SMR; P27607; -.
DR STRING; 9031.ENSGALP00000040835; -.
DR PeroxiBase; 4107; GgaPGHS02.
DR PaxDb; P27607; -.
DR Ensembl; ENSGALT00000047966; ENSGALP00000054904; ENSGALG00000033635.
DR GeneID; 396451; -.
DR KEGG; gga:396451; -.
DR CTD; 5743; -.
DR VEuPathDB; HostDB:geneid_396451; -.
DR eggNOG; KOG2408; Eukaryota.
DR GeneTree; ENSGT00390000010743; -.
DR HOGENOM; CLU_022428_0_0_1; -.
DR InParanoid; P27607; -.
DR OrthoDB; 324380at2759; -.
DR PhylomeDB; P27607; -.
DR TreeFam; TF329675; -.
DR UniPathway; UPA00662; -.
DR PRO; PR:P27607; -.
DR Proteomes; UP000000539; Chromosome 8.
DR Bgee; ENSGALG00000033635; Expressed in spermatocyte and 12 other tissues.
DR ExpressionAtlas; P27607; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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; 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:0019371; P:cyclooxygenase pathway; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; 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 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 Oxidoreductase; Peroxidase; Prostaglandin biosynthesis;
KW Prostaglandin metabolism; Reference proteome; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..603
FT /note="Prostaglandin G/H synthase 2"
FT /id="PRO_0000023881"
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 CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
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"
SQ SEQUENCE 603 AA; 69112 MW; BF6DFB337118B231 CRC64;
MLLPCALLAA LLAAGHAANP CCSLPCQNRG VCMTTGFDRY ECDCTRTGYY GENCTTPEFF
TWLKLILKPT PNTVHYILTH FKGVWNIINN ISFLRDTIMR YVLTSRSHLI DSPPTYNSDY
SYKSWEAYSN LSYYTRSLPP VGHDCPTPMG VKGKKELPDS KLIVEKFLLR RKFIPDPQGT
NVMFTFFAQH FTHQFFKTDH KKGPGFTKAY GHGVDLNHIY GETLERQLKL RLRKDGKLKY
QMIDGEMYPP TVKDTQAEMI YPPHVPEHLQ FSVGQEVFGL VPGLMMYATI WLREHNRVCD
VLKQEHPEWD DEQLFQTTRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE LLFNQRFQYQ
NRIAAEFNTL YHWHPLLPDT FQIHNQEYTF QQFLYNNSIM LEHGLSHMVK SFSKQSAGRV
AGGKNVPAAV QKVAKASIDQ SRQMRYQSLN EYRKRFMLKP FKSFEELTGE KEMAAELEEL
YGDIDAMELY PGLLVEKPRP GAIFGETMVE IGAPFSLKGL MGNTICSPEY WKPSTFGGKV
GFEIINTASL QKLICNNVKG CPFTAFHVLN PEPTEATINV STSNTAMEDI NPTLLLKEQS
AEL
