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P79208

- PGH2_SHEEP

UniProt

P79208 - PGH2_SHEEP

Protein

Prostaglandin G/H synthase 2

Gene

PTGS2

Organism
Ovis aries (Sheep)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 116 (01 Oct 2014)
      Sequence version 1 (01 May 1997)
      Previous versions | rss
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    Functioni

    Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.1 Publication

    Catalytic activityi

    Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O.

    Cofactori

    Binds 1 heme B (iron-protoporphyrin IX) group per subunit.By similarity

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei105 – 1051SubstrateBy similarity
    Active sitei192 – 1921Proton acceptorPROSITE-ProRule annotation
    Binding sitei340 – 3401SubstrateBy similarity
    Active sitei370 – 3701For cyclooxygenase activityBy similarity
    Binding sitei370 – 3701SubstrateBy similarity
    Metal bindingi373 – 3731Iron (heme axial ligand)PROSITE-ProRule annotation
    Sitei515 – 5151Aspirin-acetylated serineBy similarity

    GO - Molecular functioni

    1. dioxygenase activity Source: UniProtKB-KW
    2. heme binding Source: UniProtKB
    3. metal ion binding Source: UniProtKB-KW
    4. peroxidase activity Source: UniProtKB-KW
    5. prostaglandin-endoperoxide synthase activity Source: UniProtKB

    GO - Biological processi

    1. cyclooxygenase pathway Source: UniProtKB
    2. prostaglandin biosynthetic process Source: UniProtKB
    3. regulation of blood pressure Source: UniProtKB
    4. response to oxidative stress Source: InterPro

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase, Peroxidase

    Keywords - Biological processi

    Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    BRENDAi1.14.99.1. 4472.
    UniPathwayiUPA00662.

    Protein family/group databases

    PeroxiBasei4122. OarPGHS02.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prostaglandin G/H synthase 2 (EC:1.14.99.1)
    Alternative name(s):
    Cyclooxygenase-2
    Short name:
    COX-2
    PHS II
    Prostaglandin H2 synthase 2
    Short name:
    PGH synthase 2
    Short name:
    PGHS-2
    Prostaglandin-endoperoxide synthase 2
    Gene namesi
    Name:PTGS2
    Synonyms:COX2
    OrganismiOvis aries (Sheep)
    Taxonomic identifieri9940 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis
    ProteomesiUP000002356: Unplaced

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 16161 PublicationAdd
    BLAST
    Chaini17 – 603587Prostaglandin G/H synthase 2PRO_0000023880Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi20 ↔ 31By similarity
    Disulfide bondi21 ↔ 144By similarity
    Disulfide bondi25 ↔ 41By similarity
    Disulfide bondi43 ↔ 53By similarity
    Glycosylationi52 – 521N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi129 – 1291N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi395 – 3951N-linked (GlcNAc...)Sequence Analysis
    Modified residuei525 – 5251S-nitrosocysteineBy similarity
    Disulfide bondi554 ↔ 560By similarity
    Glycosylationi579 – 5791N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-525 By similarity.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, S-nitrosylation

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP79208.
    SMRiP79208. Positions 17-568.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini17 – 5438EGF-likePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the prostaglandin G/H synthase family.Curated
    Contains 1 EGF-like domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    HOVERGENiHBG000366.

    Family and domain databases

    Gene3Di1.10.640.10. 1 hit.
    InterProiIPR029576. COX-2.
    IPR000742. EG-like_dom.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    [Graphical view]
    PANTHERiPTHR11903:SF8. PTHR11903:SF8. 1 hit.
    PfamiPF03098. An_peroxidase. 1 hit.
    [Graphical view]
    PRINTSiPR00457. ANPEROXIDASE.
    SMARTiSM00181. EGF. 1 hit.
    [Graphical view]
    SUPFAMiSSF48113. SSF48113. 1 hit.
    PROSITEiPS50026. EGF_3. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P79208-1 [UniParc]FASTAAdd to Basket

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    MLARALLLCA AVVCGAANPC CSHPCQNRGV CMSVGFDQYK CDCTRTGFYG    50
    ENCTTPEFLT RIKLLLKPTP DTVHYILTHF KGVWNIVNKI SFLRNMIMRY 100
    VLTSRSHLIE SPPTYNVHYS YKSWEAFSNL SYYTRALPPV PDDCPTPMGV 150
    KGRKELPDSK EVVKKVLLRR KFIPDPQGTN LMFAFFAQHF THQFFKTDIE 200
    RGPAFTKGKN HGVDLSHVYG ESLERQHNRR LFKDGKMKYQ MINGEMYPPT 250
    VKDTQVEMIY PPHIPEHLKF AVGQEVFGLV PGLMMYATIW LREHNRVCDV 300
    LKQEHPEWGD EQLFQTSRLI LIGETIKIVI EDYVQHLSGY HFKLKFDPEL 350
    LFNQQFQYQN RIAAEFNTLY HWHPLLPDVF QIDGQEYNYQ QFIYNNSVLL 400
    EHGVTQFVES FTRQIAGRVA GRRNLPAAVE KVSKASLDQS REMKYQSFNE 450
    YRKRFLLKPY ESFEELTGEK EMAAELEALY GDIDAMELYP ALLVEKPAPD 500
    AIFGETMVEA GAPFSLKGLM GNPICSPEYW KPSTFGGEVG FKIINTASIQ 550
    SLICSNVKGC PFTSFSVQDA HLTKTVTINA SSSHSGLDDI NPTVLLKERS 600
    TEL 603
    Length:603
    Mass (Da):68,969
    Last modified:May 1, 1997 - v1
    Checksum:iE27F5E0549BB1C52
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti99 – 1013RYV → GYK AA sequence (PubMed:7503555)Curated
    Sequence conflicti252 – 2521K → KH AA sequence (PubMed:7503555)Curated
    Sequence conflicti256 – 2561V → N AA sequence (PubMed:7503555)Curated
    Sequence conflicti520 – 5201Missing AA sequence (PubMed:7503555)Curated
    Sequence conflicti528 – 5281E → A AA sequence (PubMed:7503555)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U68486 mRNA. Translation: AAC48684.1.
    PIRiJC5063.
    RefSeqiNP_001009432.1. NM_001009432.1.
    UniGeneiOar.642.

    Genome annotation databases

    GeneIDi443460.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U68486 mRNA. Translation: AAC48684.1 .
    PIRi JC5063.
    RefSeqi NP_001009432.1. NM_001009432.1.
    UniGenei Oar.642.

    3D structure databases

    ProteinModelPortali P79208.
    SMRi P79208. Positions 17-568.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P79208.
    ChEMBLi CHEMBL4102.

    Protein family/group databases

    PeroxiBasei 4122. OarPGHS02.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 443460.

    Organism-specific databases

    CTDi 5743.

    Phylogenomic databases

    HOVERGENi HBG000366.

    Enzyme and pathway databases

    UniPathwayi UPA00662 .
    BRENDAi 1.14.99.1. 4472.

    Family and domain databases

    Gene3Di 1.10.640.10. 1 hit.
    InterProi IPR029576. COX-2.
    IPR000742. EG-like_dom.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    [Graphical view ]
    PANTHERi PTHR11903:SF8. PTHR11903:SF8. 1 hit.
    Pfami PF03098. An_peroxidase. 1 hit.
    [Graphical view ]
    PRINTSi PR00457. ANPEROXIDASE.
    SMARTi SM00181. EGF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48113. SSF48113. 1 hit.
    PROSITEi PS50026. EGF_3. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning, functional expression, and selective regulation of ovine prostaglandin H synthase-2."
      Zhang V., O'Sullivan M., Hussain H., Roswit W.T., Holtzman M.J.
      Biochem. Biophys. Res. Commun. 227:499-506(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Purification and characterization of prostaglandin H synthase-2 from sheep placental cotyledons."
      Johnson J.L., Wimsatt J., Buckel S.D., Dyer R.D., Maddipati K.R.
      Arch. Biochem. Biophys. 324:26-34(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 17-52; 99-115; 183-196; 247-257; 286-306; 444-454; 473-485 AND 508-532.
      Tissue: Placenta.
    3. "Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition."
      Marnett L.J., Rowlinson S.W., Goodwin D.C., Kalgutkar A.S., Lanzo C.A.
      J. Biol. Chem. 274:22903-22906(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AND INHIBITION BY NSAIDS.

    Entry informationi

    Entry nameiPGH2_SHEEP
    AccessioniPrimary (citable) accession number: P79208
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 15, 1998
    Last sequence update: May 1, 1997
    Last modified: October 1, 2014
    This is version 116 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    The conversion of arachidonate to prostaglandin H2 is a 2 step reaction: a cyclooxygenase (COX) reaction which converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The nonsteroidal anti-inflammatory drugs (NSAIDs) binding site corresponds to the cyclooxygenase active site.
    Conversion of arachidonate to prostaglandin H2 is mediated by 2 different isozymes: the constitutive PTGS1 and the inducible PTGS2. PGHS1 is expressed constitutively and generally produces prostanoids acutely in response to hormonal stimuli to fine-tune physiological processes requiring instantaneous, continuous regulation (e.g. hemostasis). PGHS2 is inducible and typically produces prostanoids that mediate responses to physiological stresses such as infection and inflammation.
    PTGS1 and PTGS2 are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is able to produce an irreversible inactivation of the enzyme through a serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. PTGS2 is the principal isozyme responsible for production of inflammatory prostaglandins. New generation PTGSs inhibitors strive to be selective for PTGS2, to avoid side effects such as gastrointestinal complications and ulceration.

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3