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Q63921

- PGH1_RAT

UniProt

Q63921 - PGH1_RAT

Protein

Prostaglandin G/H synthase 1

Gene

Ptgs1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 2 (15 Dec 1998)
      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. lipid binding Source: RGD
    4. metal ion binding Source: UniProtKB-KW
    5. peroxidase activity Source: UniProtKB-KW
    6. prostaglandin-endoperoxide synthase activity Source: RGD

    GO - Biological processi

    1. aging Source: RGD
    2. learning Source: RGD
    3. maintenance of blood-brain barrier Source: RGD
    4. memory Source: RGD
    5. negative regulation of epinephrine secretion Source: RGD
    6. negative regulation of norepinephrine secretion Source: RGD
    7. positive regulation of smooth muscle contraction Source: RGD
    8. positive regulation of vasoconstriction Source: RGD
    9. prostaglandin biosynthetic process Source: UniProtKB
    10. regulation of blood pressure Source: UniProtKB
    11. response to corticosterone Source: RGD
    12. response to fatty acid Source: RGD
    13. response to organonitrogen compound Source: RGD
    14. response to oxidative stress Source: InterPro
    15. sensory perception of pain Source: RGD

    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

    UniPathwayiUPA00662.

    Protein family/group databases

    PeroxiBasei3974. RnoPGHS01.

    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
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi3439. Ptgs1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. intracellular membrane-bounded organelle Source: UniProtKB
    4. nuclear envelope Source: RGD
    5. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2626By similarityAdd
    BLAST
    Chaini27 – 602576Prostaglandin G/H synthase 1PRO_0000023870Add
    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
    Glycosylationi412 – 4121N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi571 ↔ 577By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ63921.
    PRIDEiQ63921.

    Expressioni

    Gene expression databases

    GenevestigatoriQ63921.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000010218.

    Structurei

    3D structure databases

    ProteinModelPortaliQ63921.
    SMRiQ63921. 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.
    InParanoidiQ63921.
    PhylomeDBiQ63921.

    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.

    Q63921-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSRRSLSLQF PLLLLLLLLP PPPVLLTDAG VPSPVNPCCY YPCQNQGVCV    50
    RFGLDHYQCD CTRTGYSGPN CTIPEIWTWL RSSLRPSPSF THFLLTHGYW 100
    IWEFVNATFI REVLMRLVIT VRSNLIPSPP TYNTAHDYIS WESFSNVSYY 150
    TRILPSVPKD CPTPMGTKGK KQLPDIHLLA QRLLLRREFI PGPQGTNVLF 200
    AFFAQHFTHQ FFKTSGKMGP GFTKALGHGV DLGHIYGDSL ERQYHLRLFK 250
    DGKLKYQVLD GEVYPPSVEQ ASVLMRYPPG VPPEKQMAVG QEVFGLLPGL 300
    MLFSTIWLRE HNRVCDLLKE EHPTWDDEQL FQTTRLILIG ETIKIIIEEY 350
    VQHLSGYFLQ LKFDPELLFR AQFQYRNRIA LEFNHLYHWH PLMPDSFQVG 400
    SQEYSYEQFL FNTSMLVDYG VEALVDAFSR QRAGRIGGGR NFDYHVLHVA 450
    EDVIKESREM RLQSFNEYRK RFGLKPYTSF QEFTGEKEMA AELEELYGDI 500
    DALEFYPGLM LEKCQPNSLF GESMIEMGAP FSLKGLLGNP ICSPEYWKPS 550
    TFGGDVGFNI VNTASLKKLV CLNTKTCPYV SFRVPDYPGD DGSVFVRPST 600
    EL 602
    Length:602
    Mass (Da):69,032
    Last modified:December 15, 1998 - v2
    Checksum:i0BFAF7EBFDA0C7C2
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti36 – 361N → I in AAA03465. (PubMed:8274023)Curated
    Sequence conflicti36 – 361N → I in AAB29400. (PubMed:8274023)Curated
    Sequence conflicti116 – 1172RL → GW(PubMed:8274023)Curated
    Sequence conflicti119 – 1191I → L(PubMed:8274023)Curated
    Sequence conflicti192 – 1921G → A in AAA03465. (PubMed:8274023)Curated
    Sequence conflicti192 – 1921G → A in AAB29400. (PubMed:8274023)Curated
    Sequence conflicti263 – 2631V → L in AAA03465. (PubMed:8274023)Curated
    Sequence conflicti263 – 2631V → L in AAB29400. (PubMed:8274023)Curated
    Sequence conflicti274 – 2741L → K in AAA03465. (PubMed:8274023)Curated
    Sequence conflicti274 – 2741L → K in AAB29400. (PubMed:8274023)Curated
    Sequence conflicti290 – 2901G → A in AAA03465. (PubMed:8274023)Curated
    Sequence conflicti290 – 2901G → A in AAB29400. (PubMed:8274023)Curated
    Sequence conflicti339 – 3391I → R in AAB29400. (PubMed:8274023)Curated
    Sequence conflicti344 – 3441K → E in AAA03465. (PubMed:8274023)Curated
    Sequence conflicti344 – 3441K → E in AAB29400. (PubMed:8274023)Curated
    Sequence conflicti381 – 3811L → M in AAA03465. (PubMed:8274023)Curated
    Sequence conflicti381 – 3811L → M in AAB29400. (PubMed:8274023)Curated
    Sequence conflicti392 – 3921L → F in AAA03465. (PubMed:8274023)Curated
    Sequence conflicti392 – 3921L → F in AAB29400. (PubMed:8274023)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U03388 mRNA. Translation: AAA03465.1.
    S67721 mRNA. Translation: AAB29400.2.
    U18060 mRNA. Translation: AAA85823.1.
    PIRiS39782.
    S69198.
    UniGeneiRn.44404.

    Genome annotation databases

    UCSCiRGD:3439. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U03388 mRNA. Translation: AAA03465.1 .
    S67721 mRNA. Translation: AAB29400.2 .
    U18060 mRNA. Translation: AAA85823.1 .
    PIRi S39782.
    S69198.
    UniGenei Rn.44404.

    3D structure databases

    ProteinModelPortali Q63921.
    SMRi Q63921. Positions 34-586.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000010218.

    Chemistry

    BindingDBi Q63921.
    ChEMBLi CHEMBL2095157.

    Protein family/group databases

    PeroxiBasei 3974. RnoPGHS01.

    Proteomic databases

    PaxDbi Q63921.
    PRIDEi Q63921.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    UCSCi RGD:3439. rat.

    Organism-specific databases

    RGDi 3439. Ptgs1.

    Phylogenomic databases

    eggNOGi NOG39991.
    HOGENOMi HOG000013149.
    HOVERGENi HBG000366.
    InParanoidi Q63921.
    PhylomeDBi Q63921.

    Enzyme and pathway databases

    UniPathwayi UPA00662 .

    Miscellaneous databases

    NextBioi 604139.
    PROi Q63921.

    Gene expression databases

    Genevestigatori Q63921.

    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. "Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression."
      Feng L., Sun W., Xia Y., Tang W.W., Chanmugam P., Soyoola E., Wilson C.B., Hwang D.
      Arch. Biochem. Biophys. 307:361-368(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Sprague-Dawley.
    2. "Analysis and quantitation of splicing variants of the TPA-inducible PGHS-1 mRNA in rat tracheal epithelial cells."
      Kitzler J., Hill E., Hardman R., Reddy N., Philpot R., Eling T.E.
      Arch. Biochem. Biophys. 316:856-863(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Fischer 344.
      Tissue: Trachea.
    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_RAT
    AccessioniPrimary (citable) accession number: Q63921
    Secondary accession number(s): Q62731, Q63684
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 15, 1998
    Last sequence update: December 15, 1998
    Last modified: October 1, 2014
    This is version 134 of the entry and version 2 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