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P27607

- PGH2_CHICK

UniProt

P27607 - PGH2_CHICK

Protein

Prostaglandin G/H synthase 2

Gene

PTGS2

Organism
Gallus gallus (Chicken)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 1 (01 Aug 1992)
      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 By similarity.By similarity

    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 sitei106 – 1061SubstrateBy similarity
    Active sitei193 – 1931Proton acceptorPROSITE-ProRule annotation
    Binding sitei341 – 3411SubstrateBy similarity
    Active sitei371 – 3711For cyclooxygenase activityBy similarity
    Binding sitei371 – 3711SubstrateBy similarity
    Metal bindingi374 – 3741Iron (heme axial ligand)PROSITE-ProRule annotation
    Sitei516 – 5161Aspirin-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

    ReactomeiREACT_194363. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    REACT_198071. Synthesis of 15-eicosatetraenoic acid derivatives.
    UniPathwayiUPA00662.

    Protein family/group databases

    PeroxiBasei4107. GgaPGHS02.

    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
    Mitogen-inducible PGHS
    PHS II
    Prostaglandin H2 synthase 2
    Short name:
    PGH synthase 2
    Short name:
    PGHS-2
    Prostaglandin-endoperoxide synthase 2
    Gene namesi
    Name:PTGS2
    Synonyms:CEF-147
    OrganismiGallus gallus (Chicken)
    Taxonomic identifieri9031 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus
    ProteomesiUP000000539: 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 – 1717Sequence AnalysisAdd
    BLAST
    Chaini18 – 603586Prostaglandin G/H synthase 2PRO_0000023881Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi21 ↔ 32By similarity
    Disulfide bondi22 ↔ 145By similarity
    Disulfide bondi26 ↔ 42By similarity
    Disulfide bondi44 ↔ 54By similarity
    Glycosylationi53 – 531N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi90 – 901N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi130 – 1301N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi555 ↔ 561By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP27607.

    Expressioni

    Inductioni

    By cytokines and mitogens.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    STRINGi9031.ENSGALP00000008111.

    Structurei

    3D structure databases

    ProteinModelPortaliP27607.
    SMRiP27607. Positions 18-568.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini18 – 5538EGF-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

    eggNOGiNOG39991.
    HOGENOMiHOG000013149.
    HOVERGENiHBG000366.
    InParanoidiP27607.
    KOiK11987.
    OMAiICNNVKG.
    OrthoDBiEOG7RFTHC.
    PhylomeDBiP27607.
    TreeFamiTF329675.

    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. 2 hits.
    [Graphical view]
    PRINTSiPR00457. ANPEROXIDASE.
    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.

    P27607-1 [UniParc]FASTAAdd to Basket

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    MLLPCALLAA LLAAGHAANP CCSLPCQNRG VCMTTGFDRY ECDCTRTGYY    50
    GENCTTPEFF TWLKLILKPT PNTVHYILTH FKGVWNIINN ISFLRDTIMR 100
    YVLTSRSHLI DSPPTYNSDY SYKSWEAYSN LSYYTRSLPP VGHDCPTPMG 150
    VKGKKELPDS KLIVEKFLLR RKFIPDPQGT NVMFTFFAQH FTHQFFKTDH 200
    KKGPGFTKAY GHGVDLNHIY GETLERQLKL RLRKDGKLKY QMIDGEMYPP 250
    TVKDTQAEMI YPPHVPEHLQ FSVGQEVFGL VPGLMMYATI WLREHNRVCD 300
    VLKQEHPEWD DEQLFQTTRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE 350
    LLFNQRFQYQ NRIAAEFNTL YHWHPLLPDT FQIHNQEYTF QQFLYNNSIM 400
    LEHGLSHMVK SFSKQSAGRV AGGKNVPAAV QKVAKASIDQ SRQMRYQSLN 450
    EYRKRFMLKP FKSFEELTGE KEMAAELEEL YGDIDAMELY PGLLVEKPRP 500
    GAIFGETMVE IGAPFSLKGL MGNTICSPEY WKPSTFGGKV GFEIINTASL 550
    QKLICNNVKG CPFTAFHVLN PEPTEATINV STSNTAMEDI NPTLLLKEQS 600
    AEL 603
    Length:603
    Mass (Da):69,112
    Last modified:August 1, 1992 - v1
    Checksum:iBF6DFB337118B231
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M64990 mRNA. Translation: AAA49050.1.
    PIRiA38630.
    RefSeqiNP_001161190.1. NM_001167718.1.
    NP_001161191.1. NM_001167719.1.
    UniGeneiGga.4401.

    Genome annotation databases

    GeneIDi396451.
    KEGGigga:396451.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M64990 mRNA. Translation: AAA49050.1 .
    PIRi A38630.
    RefSeqi NP_001161190.1. NM_001167718.1.
    NP_001161191.1. NM_001167719.1.
    UniGenei Gga.4401.

    3D structure databases

    ProteinModelPortali P27607.
    SMRi P27607. Positions 18-568.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9031.ENSGALP00000008111.

    Protein family/group databases

    PeroxiBasei 4107. GgaPGHS02.

    Proteomic databases

    PaxDbi P27607.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 396451.
    KEGGi gga:396451.

    Organism-specific databases

    CTDi 5743.

    Phylogenomic databases

    eggNOGi NOG39991.
    HOGENOMi HOG000013149.
    HOVERGENi HBG000366.
    InParanoidi P27607.
    KOi K11987.
    OMAi ICNNVKG.
    OrthoDBi EOG7RFTHC.
    PhylomeDBi P27607.
    TreeFami TF329675.

    Enzyme and pathway databases

    UniPathwayi UPA00662 .
    Reactomei REACT_194363. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    REACT_198071. Synthesis of 15-eicosatetraenoic acid derivatives.

    Miscellaneous databases

    NextBioi 20816492.
    PROi P27607.

    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. 2 hits.
    [Graphical view ]
    PRINTSi PR00457. ANPEROXIDASE.
    SUPFAMi SSF48113. SSF48113. 1 hit.
    PROSITEi PS50026. EGF_3. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing."
      Xie W., Chipman J.G., Robertson D.L., Erikson R.L., Simmons D.L.
      Proc. Natl. Acad. Sci. U.S.A. 88:2692-2696(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].

    Entry informationi

    Entry nameiPGH2_CHICK
    AccessioniPrimary (citable) accession number: P27607
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: August 1, 1992
    Last modified: October 1, 2014
    This is version 126 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, 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