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Database: UniProt/SWISS-PROT
Entry: PGH2_BOVIN
LinkDB: PGH2_BOVIN
Original site: PGH2_BOVIN 
ID   PGH2_BOVIN              Reviewed;         604 AA.
AC   O62698; O46517; O62665;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-1998, sequence version 2.
DT   05-DEC-2018, entry version 145.
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=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=COX2;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
OC   Pecora; Bovidae; Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=11207216; DOI=10.1095/biolreprod64.3.983;
RA   Liu J., Antaya M., Goff A.K., Boerboom D., Silversides D.W.,
RA   Lussier J.G., Sirois J.;
RT   "Molecular characterization of bovine prostaglandin G/H synthase-2 and
RT   regulation in uterine stromal cells.";
RL   Biol. Reprod. 64:983-991(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 105-253.
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
RT   F2alpha production in endometrial epithelial cells in vitro: role of
RT   cyclooxygenase-2.";
RL   Endocrinology 138:4798-4805(1997).
CC   -!- FUNCTION: Converts arachidonate to prostaglandin H2 (PGH2), a
CC       committed step in prostanoid synthesis. Constitutively expressed
CC       in some tissues in physiological conditions, such as the
CC       endothelium, kidney and brain, and in pathological conditions,
CC       such as in cancer. PTGS2 is responsible for production of
CC       inflammatory prostaglandins. Up-regulation of PTGS2 is also
CC       associated with increased cell adhesion, phenotypic changes,
CC       resistance to apoptosis and tumor angiogenesis. In cancer cells,
CC       PTGS2 is a key step in the production of prostaglandin E2 (PGE2),
CC       which plays important roles in modulating motility, proliferation
CC       and resistance to 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
CC       subunit. {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
CC       protein. Endoplasmic reticulum membrane; Peripheral membrane
CC       protein.
CC   -!- PTM: S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-
CC       nitrosylation may take place on different Cys residues in addition
CC       to Cys-526 (By similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: The conversion of arachidonate to prostaglandin H2
CC       is a 2 step reaction: a cyclooxygenase (COX) reaction which
CC       converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase
CC       reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The
CC       cyclooxygenase reaction occurs in a hydrophobic channel in the
CC       core of the enzyme. The peroxidase reaction occurs at a heme-
CC       containing active site located near the protein surface. The
CC       nonsteroidal anti-inflammatory drugs (NSAIDs) binding site
CC       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. PGHS1 is expressed constitutively and generally
CC       produces prostanoids acutely in response to hormonal stimuli to
CC       fine-tune physiological processes requiring instantaneous,
CC       continuous regulation (e.g. hemostasis). PGHS2 is inducible and
CC       typically produces prostanoids that mediate responses to
CC       physiological stresses such as infection and inflammation.
CC   -!- MISCELLANEOUS: PTGS1 and PTGS2 are the targets of nonsteroidal
CC       anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen.
CC       Aspirin is able to produce an irreversible inactivation of the
CC       enzyme through a serine acetylation. Inhibition of the PGHSs with
CC       NSAIDs acutely reduces inflammation, pain, and fever, and long-
CC       term use of these drugs reduces fatal thrombotic events, as well
CC       as the development of colon cancer and Alzheimer's disease. PTGS2
CC       is the principal isozyme responsible for production of
CC       inflammatory prostaglandins. New generation PTGSs inhibitors
CC       strive to be selective for PTGS2, to avoid side effects such as
CC       gastrointestinal complications and ulceration.
CC   -!- SIMILARITY: Belongs to the prostaglandin G/H synthase family.
CC       {ECO:0000305}.
DR   EMBL; AF031698; AAC04702.1; -; mRNA.
DR   EMBL; AF031699; AAC28562.1; -; Genomic_DNA.
DR   EMBL; AF004944; AAC05592.1; -; mRNA.
DR   RefSeq; NP_776870.1; NM_174445.2.
DR   UniGene; Bt.15758; -.
DR   ProteinModelPortal; O62698; -.
DR   SMR; O62698; -.
DR   STRING; 9913.ENSBTAP00000018774; -.
DR   BindingDB; O62698; -.
DR   ChEMBL; CHEMBL3331; -.
DR   PeroxiBase; 3330; BtPGHS02.
DR   PaxDb; O62698; -.
DR   PRIDE; O62698; -.
DR   GeneID; 282023; -.
DR   KEGG; bta:282023; -.
DR   CTD; 5743; -.
DR   eggNOG; KOG2408; Eukaryota.
DR   eggNOG; ENOG410XPZ3; LUCA.
DR   HOGENOM; HOG000013149; -.
DR   HOVERGEN; HBG000366; -.
DR   InParanoid; O62698; -.
DR   KO; K11987; -.
DR   BRENDA; 1.14.99.1; 908.
DR   UniPathway; UPA00662; -.
DR   PRO; PR:O62698; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0004666; F:prostaglandin-endoperoxide synthase activity; ISS:UniProtKB.
DR   GO; GO:0071347; P:cellular response to interleukin-1; IMP:AgBase.
DR   GO; GO:0019371; P:cyclooxygenase pathway; ISS:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR   GO; GO:0000212; P:meiotic spindle organization; IMP:AgBase.
DR   GO; GO:0001550; P:ovarian cumulus expansion; IMP:AgBase.
DR   GO; GO:0040019; P:positive regulation of embryonic development; IMP:AgBase.
DR   GO; GO:1904146; P:positive regulation of meiotic cell cycle process involved in oocyte maturation; IMP:AgBase.
DR   GO; GO:1900195; P:positive regulation of oocyte maturation; IMP:AgBase.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:AgBase.
DR   GO; GO:0001516; P:prostaglandin biosynthetic process; IMP:AgBase.
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; IPR029576; COX-2.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR010255; Haem_peroxidase.
DR   InterPro; IPR019791; Haem_peroxidase_animal.
DR   InterPro; IPR037120; Haem_peroxidase_sf.
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   Complete proteome; Dioxygenase; Disulfide bond; Endoplasmic reticulum;
KW   Fatty acid biosynthesis; Fatty acid metabolism; Glycoprotein; Heme;
KW   Iron; Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding;
KW   Microsome; Oxidoreductase; Peroxidase; Prostaglandin biosynthesis;
KW   Prostaglandin metabolism; Reference proteome; S-nitrosylation; Signal.
FT   SIGNAL        1     17       {ECO:0000250}.
FT   CHAIN        18    604       Prostaglandin G/H synthase 2.
FT                                /FTId=PRO_0000023872.
FT   DOMAIN       18     55       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   ACT_SITE    193    193       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00298}.
FT   ACT_SITE    371    371       For cyclooxygenase activity.
FT                                {ECO:0000250|UniProtKB:Q05769}.
FT   METAL       374    374       Iron (heme axial ligand).
FT                                {ECO:0000255|PROSITE-ProRule:PRU00298}.
FT   BINDING     106    106       Substrate.
FT                                {ECO:0000250|UniProtKB:Q05769}.
FT   BINDING     341    341       Substrate.
FT                                {ECO:0000250|UniProtKB:Q05769}.
FT   SITE        516    516       Aspirin-acetylated serine.
FT                                {ECO:0000250|UniProtKB:P35354}.
FT   CARBOHYD     53     53       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    130    130       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    396    396       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    580    580       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     21     32       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID     22    145       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID     26     42       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID     44     54       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID    555    561       {ECO:0000250|UniProtKB:Q05769}.
FT   CONFLICT      6      6       L -> M (in Ref. 1; AAC28562).
FT                                {ECO:0000305}.
FT   CONFLICT    111    111       E -> D (in Ref. 2; AAC05592).
FT                                {ECO:0000305}.
FT   CONFLICT    458    458       V -> L (in Ref. 1; AAC28562).
FT                                {ECO:0000305}.
SQ   SEQUENCE   604 AA;  69163 MW;  16EA2E51D0A01A45 CRC64;
     MLARALLLCA AVALSGAANP CCSHPCQNRG VCMSVGFDQY KCDCTRTGFY GENCTTPEFL
     TRIKLLLKPT PNTVHYILTH FKGVWNIVNK ISFLRNMIMR YVLTSRSHLI ESPPTYNVHY
     SYKSWEAFSN LSYYTRALPP VPDDCPTPMG VKGRKELPDS KEVVKKVLLR RKFIPDPQGT
     NLMFAFFAQH FTHQFFKTDF ERGPAFTKGK NHGVDLSHIY GESLERQHKL RLFKDGKMKY
     QMINGEMYPP TVKDTQVEMI YPPHVPEHLK FAVGQEVFGL VPGLMMYATI WLREHNRVCD
     VLKQEHPEWG DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE LLFNQQFQYQ
     NRIAAEFNTL YHWHPLLPDV FQIDGQEYNY QQFIYNNSVL LEHGLTQFVE SFTRQRAGRV
     AGGRNLPVAV EKVSKASIDQ SREMKYQSFN EYRKRFLVKP YESFEELTGE KEMAAELEAL
     YGDIDAMEFY PALLVEKPRP DAIFGETMVE AGAPFSLKGL MGNPICSPEY WKPSTFGGEV
     GFKIINTASI QSLICSNVKG CPFTSFSVQD THLTKTVTIN ASSSHSGLDD INPTVLLKER
     STEL
//
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