GenomeNet

Database: UniProt/SWISS-PROT
Entry: PGH2_SHEEP
LinkDB: PGH2_SHEEP
Original site: PGH2_SHEEP 
ID   PGH2_SHEEP              Reviewed;         603 AA.
AC   P79208;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   23-MAY-2018, entry version 136.
DE   RecName: Full=Prostaglandin G/H synthase 2;
DE            EC=1.14.99.1 {ECO:0000269|PubMed:10438452};
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   Ovis aries (Sheep).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
OC   Pecora; Bovidae; Caprinae; Ovis.
OX   NCBI_TaxID=9940;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8878543; DOI=10.1006/bbrc.1996.1536;
RA   Zhang V., O'Sullivan M., Hussain H., Roswit W.T., Holtzman M.J.;
RT   "Molecular cloning, functional expression, and selective regulation of
RT   ovine prostaglandin H synthase-2.";
RL   Biochem. Biophys. Res. Commun. 227:499-506(1996).
RN   [2]
RP   PROTEIN SEQUENCE OF 17-52; 99-115; 183-196; 247-257; 286-306; 444-454;
RP   473-485 AND 508-532.
RC   TISSUE=Placenta;
RX   PubMed=7503555; DOI=10.1006/abbi.1995.9934;
RA   Johnson J.L., Wimsatt J., Buckel S.D., Dyer R.D., Maddipati K.R.;
RT   "Purification and characterization of prostaglandin H synthase-2 from
RT   sheep placental cotyledons.";
RL   Arch. Biochem. Biophys. 324:26-34(1995).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, AND INHIBITION BY NSAIDS.
RX   PubMed=10438452; DOI=10.1074/jbc.274.33.22903;
RA   Marnett L.J., Rowlinson S.W., Goodwin D.C., Kalgutkar A.S.,
RA   Lanzo C.A.;
RT   "Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of
RT   catalysis and inhibition.";
RL   J. Biol. Chem. 274:22903-22906(1999).
CC   -!- FUNCTION: Converts arachidonate to prostaglandin H2 (PGH2), a
CC       committed step in prostanoid synthesis (PubMed:10438452).
CC       Constitutively expressed in some tissues in physiological
CC       conditions, such as the endothelium, kidney and brain, and in
CC       pathological conditions, such as in cancer. PTGS2 is responsible
CC       for production of inflammatory prostaglandins. Up-regulation of
CC       PTGS2 is also associated with increased cell adhesion, phenotypic
CC       changes, resistance to apoptosis and tumor angiogenesis. In cancer
CC       cells, PTGS2 is a key step in the production of prostaglandin E2
CC       (PGE2), which plays important roles in modulating motility,
CC       proliferation and resistance to apoptosis (By similarity).
CC       {ECO:0000250|UniProtKB:Q05769, ECO:0000269|PubMed:10438452}.
CC   -!- CATALYTIC ACTIVITY: Arachidonate + AH(2) + 2 O(2) = prostaglandin
CC       H(2) + A + H(2)O. {ECO:0000269|PubMed:10438452}.
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-525 (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; U68486; AAC48684.1; -; mRNA.
DR   PIR; JC5063; JC5063.
DR   RefSeq; NP_001009432.1; NM_001009432.1.
DR   UniGene; Oar.642; -.
DR   ProteinModelPortal; P79208; -.
DR   SMR; P79208; -.
DR   BindingDB; P79208; -.
DR   ChEMBL; CHEMBL4102; -.
DR   PeroxiBase; 4122; OarPGHS02.
DR   GeneID; 443460; -.
DR   KEGG; oas:443460; -.
DR   CTD; 5743; -.
DR   HOVERGEN; HBG000366; -.
DR   KO; K11987; -.
DR   BRENDA; 1.14.99.1; 2668.
DR   UniPathway; UPA00662; -.
DR   PRO; PR:P79208; -.
DR   Proteomes; UP000002356; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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: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; 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   1: Evidence at protein level;
KW   Complete proteome; Dioxygenase; Direct protein sequencing;
KW   Disulfide bond; Endoplasmic reticulum; Fatty acid biosynthesis;
KW   Fatty acid metabolism; Glycoprotein; Heme; Iron; Lipid biosynthesis;
KW   Lipid metabolism; Membrane; Metal-binding; Microsome; Oxidoreductase;
KW   Peroxidase; Prostaglandin biosynthesis; Prostaglandin metabolism;
KW   Reference proteome; S-nitrosylation; Signal.
FT   SIGNAL        1     16       {ECO:0000269|PubMed:7503555}.
FT   CHAIN        17    603       Prostaglandin G/H synthase 2.
FT                                /FTId=PRO_0000023880.
FT   DOMAIN       17     54       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   ACT_SITE    192    192       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00298}.
FT   ACT_SITE    370    370       For cyclooxygenase activity.
FT                                {ECO:0000250|UniProtKB:Q05769}.
FT   METAL       373    373       Iron (heme axial ligand).
FT                                {ECO:0000255|PROSITE-ProRule:PRU00298}.
FT   BINDING     105    105       Substrate.
FT                                {ECO:0000250|UniProtKB:Q05769}.
FT   BINDING     340    340       Substrate.
FT                                {ECO:0000250|UniProtKB:Q05769}.
FT   SITE        515    515       Aspirin-acetylated serine.
FT                                {ECO:0000250|UniProtKB:P35354}.
FT   CARBOHYD     52     52       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    129    129       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    395    395       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    579    579       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     20     31       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID     21    144       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID     25     41       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID     43     53       {ECO:0000250|UniProtKB:Q05769}.
FT   DISULFID    554    560       {ECO:0000250|UniProtKB:Q05769}.
FT   CONFLICT     99    101       RYV -> GYK (in Ref. 2; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT    252    252       K -> KH (in Ref. 2; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT    256    256       V -> N (in Ref. 2; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT    520    520       Missing (in Ref. 2; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT    528    528       E -> A (in Ref. 2; AA sequence).
FT                                {ECO:0000305}.
SQ   SEQUENCE   603 AA;  68969 MW;  E27F5E0549BB1C52 CRC64;
     MLARALLLCA AVVCGAANPC CSHPCQNRGV CMSVGFDQYK CDCTRTGFYG ENCTTPEFLT
     RIKLLLKPTP DTVHYILTHF KGVWNIVNKI SFLRNMIMRY VLTSRSHLIE SPPTYNVHYS
     YKSWEAFSNL SYYTRALPPV PDDCPTPMGV KGRKELPDSK EVVKKVLLRR KFIPDPQGTN
     LMFAFFAQHF THQFFKTDIE RGPAFTKGKN HGVDLSHVYG ESLERQHNRR LFKDGKMKYQ
     MINGEMYPPT VKDTQVEMIY PPHIPEHLKF AVGQEVFGLV PGLMMYATIW LREHNRVCDV
     LKQEHPEWGD EQLFQTSRLI LIGETIKIVI EDYVQHLSGY HFKLKFDPEL LFNQQFQYQN
     RIAAEFNTLY HWHPLLPDVF QIDGQEYNYQ QFIYNNSVLL EHGVTQFVES FTRQIAGRVA
     GRRNLPAAVE KVSKASLDQS REMKYQSFNE YRKRFLLKPY ESFEELTGEK EMAAELEALY
     GDIDAMELYP ALLVEKPAPD AIFGETMVEA GAPFSLKGLM GNPICSPEYW KPSTFGGEVG
     FKIINTASIQ SLICSNVKGC PFTSFSVQDA HLTKTVTINA SSSHSGLDDI NPTVLLKERS
     TEL
//
DBGET integrated database retrieval system