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P22437

- PGH1_MOUSE

UniProt

P22437 - PGH1_MOUSE

Protein

Prostaglandin G/H synthase 1

Gene

Ptgs1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 151 (01 Oct 2014)
      Sequence version 1 (01 Aug 1991)
      Previous versions | rss
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    Functioni

    Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.

    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
    Active sitei209 – 2091Proton acceptorPROSITE-ProRule annotation
    Active sitei387 – 3871For cyclooxygenase activityBy similarity
    Metal bindingi390 – 3901Iron (heme axial ligand)PROSITE-ProRule annotation
    Sitei532 – 5321Aspirin-acetylated serine

    GO - Molecular functioni

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

    GO - Biological processi

    1. cyclooxygenase pathway Source: Ensembl
    2. keratinocyte differentiation Source: UniProtKB
    3. prostaglandin biosynthetic process Source: MGI
    4. prostaglandin metabolic process Source: MGI
    5. regulation of blood pressure Source: MGI
    6. regulation of cell proliferation Source: MGI
    7. 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_188623. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    UniPathwayiUPA00662.

    Protein family/group databases

    PeroxiBasei3361. MmPGHS01.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Prostaglandin G/H synthase 1 (EC:1.14.99.1)
    Alternative name(s):
    Cyclooxygenase-1
    Short name:
    COX-1
    Prostaglandin H2 synthase 1
    Short name:
    PGH synthase 1
    Short name:
    PGHS-1
    Short name:
    PHS 1
    Prostaglandin-endoperoxide synthase 1
    Gene namesi
    Name:Ptgs1
    Synonyms:Cox-1, Cox1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:97797. Ptgs1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. photoreceptor outer segment Source: MGI

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2626Add
    BLAST
    Chaini27 – 602576Prostaglandin G/H synthase 1PRO_0000023869Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi38 ↔ 49By similarity
    Disulfide bondi39 ↔ 161By similarity
    Disulfide bondi43 ↔ 59By similarity
    Disulfide bondi61 ↔ 71By similarity
    Glycosylationi70 – 701N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi106 – 1061N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi146 – 1461N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi571 ↔ 577By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiP22437.
    PaxDbiP22437.
    PRIDEiP22437.

    PTM databases

    PhosphoSiteiP22437.

    Expressioni

    Gene expression databases

    ArrayExpressiP22437.
    BgeeiP22437.
    CleanExiMM_PTGS1.
    GenevestigatoriP22437.

    Interactioni

    Subunit structurei

    Homodimer.

    Protein-protein interaction databases

    BioGridi202462. 2 interactions.
    IntActiP22437. 3 interactions.
    MINTiMINT-4107353.

    Structurei

    3D structure databases

    ProteinModelPortaliP22437.
    SMRiP22437. Positions 34-586.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini34 – 7239EGF-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

    EGF-like domain, Signal

    Phylogenomic databases

    eggNOGiNOG39991.
    HOGENOMiHOG000013149.
    HOVERGENiHBG000366.
    InParanoidiP22437.
    KOiK00509.
    OMAiFKTSGKM.
    OrthoDBiEOG7RFTHC.
    PhylomeDBiP22437.
    TreeFamiTF329675.

    Family and domain databases

    Gene3Di1.10.640.10. 1 hit.
    InterProiIPR029580. COX-1.
    IPR000742. EG-like_dom.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    [Graphical view]
    PANTHERiPTHR11903:SF6. PTHR11903:SF6. 1 hit.
    PfamiPF03098. An_peroxidase. 2 hits.
    [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.

    P22437-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSRRSLSLWF PLLLLLLLPP TPSVLLADPG VPSPVNPCCY YPCQNQGVCV    50
    RFGLDNYQCD CTRTGYSGPN CTIPEIWTWL RNSLRPSPSF THFLLTHGYW 100
    LWEFVNATFI REVLMRLVLT VRSNLIPSPP TYNSAHDYIS WESFSNVSYY 150
    TRILPSVPKD CPTPMGTKGK KQLPDVQLLA QQLLLRREFI PAPQGTNILF 200
    AFFAQHFTHQ FFKTSGKMGP GFTKALGHGV DLGHIYGDNL ERQYHLRLFK 250
    DGKLKYQVLD GEVYPPSVEQ ASVLMRYPPG VPPERQMAVG QEVFGLLPGL 300
    MLFSTIWLRE HNRVCDLLKE EHPTWDDEQL FQTTRLILIG ETIKIVIEEY 350
    VQHLSGYFLQ LKFDPELLFR AQFQYRNRIA MEFNHLYHWH PLMPNSFQVG 400
    SQEYSYEQFL FNTSMLVDYG VEALVDAFSR QRAGRIGGGR NFDYHVLHVA 450
    VDVIKESREM RLQPFNEYRK RFGLKPYTSF QELTGEKEMA AELEELYGDI 500
    DALEFYPGLL LEKCQPNSIF GESMIEMGAP FSLKGLLGNP ICSPEYWKPS 550
    TFGGDVGFNL VNTASLKKLV CLNTKTCPYV SFRVPDYPGD DGSVLVRRST 600
    EL 602
    Length:602
    Mass (Da):69,042
    Last modified:August 1, 1991 - v1
    Checksum:i634C0E602045C3A0
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M34141 mRNA. Translation: AAA39913.1.
    BC005573 mRNA. Translation: AAH05573.1.
    CCDSiCCDS15970.1.
    PIRiA35564.
    RefSeqiNP_032995.1. NM_008969.4.
    XP_006497853.1. XM_006497790.1.
    XP_006497854.1. XM_006497791.1.
    XP_006497855.1. XM_006497792.1.
    XP_006497856.1. XM_006497793.1.
    UniGeneiMm.275434.

    Genome annotation databases

    EnsembliENSMUST00000062069; ENSMUSP00000059977; ENSMUSG00000047250.
    GeneIDi19224.
    KEGGimmu:19224.
    UCSCiuc008jll.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M34141 mRNA. Translation: AAA39913.1 .
    BC005573 mRNA. Translation: AAH05573.1 .
    CCDSi CCDS15970.1.
    PIRi A35564.
    RefSeqi NP_032995.1. NM_008969.4.
    XP_006497853.1. XM_006497790.1.
    XP_006497854.1. XM_006497791.1.
    XP_006497855.1. XM_006497792.1.
    XP_006497856.1. XM_006497793.1.
    UniGenei Mm.275434.

    3D structure databases

    ProteinModelPortali P22437.
    SMRi P22437. Positions 34-586.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202462. 2 interactions.
    IntActi P22437. 3 interactions.
    MINTi MINT-4107353.

    Chemistry

    BindingDBi P22437.
    ChEMBLi CHEMBL2649.

    Protein family/group databases

    PeroxiBasei 3361. MmPGHS01.

    PTM databases

    PhosphoSitei P22437.

    Proteomic databases

    MaxQBi P22437.
    PaxDbi P22437.
    PRIDEi P22437.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000062069 ; ENSMUSP00000059977 ; ENSMUSG00000047250 .
    GeneIDi 19224.
    KEGGi mmu:19224.
    UCSCi uc008jll.1. mouse.

    Organism-specific databases

    CTDi 5742.
    MGIi MGI:97797. Ptgs1.

    Phylogenomic databases

    eggNOGi NOG39991.
    HOGENOMi HOG000013149.
    HOVERGENi HBG000366.
    InParanoidi P22437.
    KOi K00509.
    OMAi FKTSGKM.
    OrthoDBi EOG7RFTHC.
    PhylomeDBi P22437.
    TreeFami TF329675.

    Enzyme and pathway databases

    UniPathwayi UPA00662 .
    Reactomei REACT_188623. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).

    Miscellaneous databases

    NextBioi 296008.
    PROi P22437.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P22437.
    Bgeei P22437.
    CleanExi MM_PTGS1.
    Genevestigatori P22437.

    Family and domain databases

    Gene3Di 1.10.640.10. 1 hit.
    InterProi IPR029580. COX-1.
    IPR000742. EG-like_dom.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    [Graphical view ]
    PANTHERi PTHR11903:SF6. PTHR11903:SF6. 1 hit.
    Pfami PF03098. An_peroxidase. 2 hits.
    [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. "The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases."
      Dewitt D.L., El-Harith E.A., Kraemer S.A., Andrews M.J., Yao E.F., Armstrong R.L., Smith W.L.
      J. Biol. Chem. 265:5192-5198(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Mammary gland.
    3. "Cyclooxygenases: structural, cellular, and molecular biology."
      Smith W.L., DeWitt D.L., Garavito R.M.
      Annu. Rev. Biochem. 69:145-182(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION; TISSUE SPECIFICITY AND INHIBITION BY NSAIDS.
    4. "Aspirin, cyclooxygenase inhibition and colorectal cancer."
      Sostres C., Gargallo C.J., Lanas A.
      World J. Gastrointest. Pharmacol. Ther. 5:40-49(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN COLORECTAL CANCER.

    Entry informationi

    Entry nameiPGH1_MOUSE
    AccessioniPrimary (citable) accession number: P22437
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: August 1, 1991
    Last modified: October 1, 2014
    This is version 151 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3