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Q05769

- PGH2_MOUSE

UniProt

Q05769 - PGH2_MOUSE

Protein

Prostaglandin G/H synthase 2

Gene

Ptgs2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 160 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      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.5 Publications

    Catalytic activityi

    Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O.4 Publications

    Cofactori

    Binds 1 heme B (iron-protoporphyrin IX) group per subunit.3 Publications

    Enzyme regulationi

    Inhibited by the nonsteroidal anti-inflammatory drugs aspirin, naproxen, diclofenac, meclofenamic acid, indomethacin and their analogs.2 Publications

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei106 – 1061Substrate
    Active sitei193 – 1931Proton acceptor1 PublicationPROSITE-ProRule annotation
    Binding sitei341 – 3411Substrate
    Active sitei371 – 3711For cyclooxygenase activity1 Publication
    Binding sitei371 – 3711Substrate
    Metal bindingi374 – 3741Iron (heme axial ligand)
    Sitei516 – 5161Aspirin-acetylated serine
    Sitei592 – 5921Not glycosylated

    GO - Molecular functioni

    1. heme binding Source: UniProtKB
    2. lipid binding Source: Ensembl
    3. metal ion binding Source: UniProtKB-KW
    4. oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: Ensembl
    5. peroxidase activity Source: UniProtKB-KW
    6. prostaglandin-endoperoxide synthase activity Source: UniProtKB
    7. protein homodimerization activity Source: UniProtKB

    GO - Biological processi

    1. anagen Source: MGI
    2. angiogenesis Source: Ensembl
    3. bone mineralization Source: MGI
    4. brown fat cell differentiation Source: BHF-UCL
    5. cellular response to ATP Source: Ensembl
    6. cellular response to hypoxia Source: Ensembl
    7. cellular response to mechanical stimulus Source: Ensembl
    8. cellular response to UV Source: Ensembl
    9. cyclooxygenase pathway Source: UniProtKB
    10. decidualization Source: Ensembl
    11. embryo implantation Source: Ensembl
    12. inflammatory response Source: Ensembl
    13. keratinocyte differentiation Source: UniProtKB
    14. learning Source: Ensembl
    15. maintenance of blood-brain barrier Source: Ensembl
    16. memory Source: Ensembl
    17. negative regulation of calcium ion transport Source: Ensembl
    18. negative regulation of cell cycle Source: Ensembl
    19. negative regulation of cell proliferation Source: Ensembl
    20. negative regulation of smooth muscle contraction Source: Ensembl
    21. negative regulation of synaptic transmission, dopaminergic Source: Ensembl
    22. ovulation Source: Ensembl
    23. positive regulation of apoptotic process Source: Ensembl
    24. positive regulation of brown fat cell differentiation Source: BHF-UCL
    25. positive regulation of cell migration involved in sprouting angiogenesis Source: Ensembl
    26. positive regulation of fever generation Source: BHF-UCL
    27. positive regulation of fibroblast growth factor production Source: Ensembl
    28. positive regulation of NF-kappaB import into nucleus Source: Ensembl
    29. positive regulation of nitric oxide biosynthetic process Source: Ensembl
    30. positive regulation of platelet-derived growth factor production Source: Ensembl
    31. positive regulation of smooth muscle cell proliferation Source: Ensembl
    32. positive regulation of smooth muscle contraction Source: Ensembl
    33. positive regulation of synaptic plasticity Source: Ensembl
    34. positive regulation of synaptic transmission, glutamatergic Source: Ensembl
    35. positive regulation of transforming growth factor beta production Source: Ensembl
    36. positive regulation of vasoconstriction Source: Ensembl
    37. positive regulation vascular endothelial growth factor production Source: Ensembl
    38. prostaglandin biosynthetic process Source: UniProtKB
    39. regulation of blood pressure Source: MGI
    40. regulation of cell proliferation Source: MGI
    41. response to drug Source: Ensembl
    42. response to estradiol Source: Ensembl
    43. response to fatty acid Source: Ensembl
    44. response to fructose Source: Ensembl
    45. response to glucocorticoid Source: Ensembl
    46. response to lipopolysaccharide Source: Ensembl
    47. response to lithium ion Source: Ensembl
    48. response to manganese ion Source: Ensembl
    49. response to oxidative stress Source: InterPro
    50. response to tumor necrosis factor Source: Ensembl
    51. response to vitamin D Source: Ensembl
    52. sensory perception of pain Source: Ensembl

    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).
    REACT_196559. Synthesis of 15-eicosatetraenoic acid derivatives.
    UniPathwayiUPA00662.

    Protein family/group databases

    PeroxiBasei3360. MmPGHS02.

    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
    Glucocorticoid-regulated inflammatory cyclooxygenase
    Gripghs
    Macrophage activation-associated marker protein P71/73
    PES-2
    PHS II
    Prostaglandin H2 synthase 2
    Short name:
    PGH synthase 2
    Short name:
    PGHS-2
    Prostaglandin-endoperoxide synthase 2
    TIS10 protein
    Gene namesi
    Name:Ptgs2
    Synonyms:Cox-2, Cox2, Pghs-b, Tis10
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 1

    Organism-specific databases

    MGIiMGI:97798. Ptgs2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. neuron projection Source: MGI
    4. protein complex Source: Ensembl

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Disruption phenotypei

    Mutant mice exhibit defects in colonic mucosal wound repair.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi517 – 5171L → A, F, P or T: Slightly reduced activity. 1 Publication
    Mutagenesisi580 – 5801N → A: Loss of glycosylation site. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1717Add
    BLAST
    Chaini18 – 604587Prostaglandin G/H synthase 2PRO_0000023876Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi21 ↔ 32
    Disulfide bondi22 ↔ 145
    Disulfide bondi26 ↔ 42
    Disulfide bondi44 ↔ 54
    Glycosylationi53 – 531N-linked (GlcNAc...)7 PublicationsCAR_000222
    Glycosylationi130 – 1301N-linked (GlcNAc...)7 PublicationsCAR_000223
    Glycosylationi396 – 3961N-linked (GlcNAc...)7 PublicationsCAR_000224
    Modified residuei526 – 5261S-nitrosocysteineBy similarity
    Disulfide bondi555 ↔ 561
    Glycosylationi580 – 5801N-linked (GlcNAc...)2 PublicationsCAR_000225

    Post-translational modificationi

    S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526 By similarity.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, S-nitrosylation

    Proteomic databases

    PaxDbiQ05769.
    PRIDEiQ05769.

    PTM databases

    PhosphoSiteiQ05769.
    UniCarbKBiQ05769.

    Expressioni

    Tissue specificityi

    Following colon injury, expressed in the wound bed mesenchyme during the first phase of repair, probably by colonic mesenchymal stem cells (at protein level).1 Publication

    Developmental stagei

    During colonic wound repair, highly up-regulated (more than 1600-fold) in the mesenchyme of the wound bed 2 days after injury as compared to uninjured mucosa. Further increase in expression is observed at day 4 following injury (close to 2200-fold). Down-regulated at day 6 (only 93-fold increase as compared to uninjured mucosa).1 Publication

    Inductioni

    By cytokines and mitogens.

    Gene expression databases

    BgeeiQ05769.
    CleanExiMM_PTGS2.
    GenevestigatoriQ05769.

    Interactioni

    Subunit structurei

    Homodimer.5 Publications

    Protein-protein interaction databases

    BioGridi202463. 5 interactions.
    DIPiDIP-31082N.
    IntActiQ05769. 1 interaction.

    Structurei

    Secondary structure

    1
    604
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni20 – 234
    Helixi27 – 293
    Beta strandi31 – 366
    Beta strandi39 – 435
    Beta strandi47 – 504
    Turni51 – 544
    Helixi59 – 679
    Helixi71 – 788
    Helixi82 – 898
    Helixi92 – 10716
    Beta strandi117 – 1193
    Beta strandi120 – 1223
    Helixi125 – 1295
    Beta strandi131 – 1333
    Beta strandi135 – 1384
    Beta strandi145 – 1473
    Beta strandi150 – 1534
    Helixi160 – 1678
    Helixi182 – 19211
    Turni193 – 1953
    Turni200 – 2023
    Beta strandi206 – 2083
    Beta strandi213 – 2153
    Helixi217 – 2204
    Helixi224 – 2307
    Beta strandi241 – 2433
    Beta strandi246 – 2483
    Helixi252 – 2554
    Beta strandi263 – 2653
    Helixi267 – 2693
    Turni276 – 2794
    Helixi282 – 30524
    Helixi311 – 33222
    Helixi334 – 3396
    Helixi349 – 3524
    Helixi365 – 3706
    Helixi374 – 3763
    Beta strandi379 – 3835
    Beta strandi386 – 3883
    Helixi390 – 3934
    Helixi398 – 41417
    Beta strandi420 – 4245
    Helixi428 – 4303
    Helixi431 – 44313
    Helixi449 – 4557
    Helixi464 – 4685
    Beta strandi469 – 4713
    Helixi472 – 48110
    Helixi484 – 4863
    Helixi489 – 4957
    Beta strandi503 – 5053
    Helixi506 – 52116
    Helixi524 – 5263
    Turni528 – 5303
    Helixi533 – 5364
    Helixi539 – 5468
    Helixi550 – 5578
    Beta strandi558 – 5603

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CVUX-ray2.40A/B18-569[»]
    1CX2X-ray3.00A/B/C/D18-604[»]
    1DCXmodel-A/B18-569[»]
    1DD0model-A/B18-569[»]
    1DDXX-ray3.00A/B/C/D18-569[»]
    1PXXX-ray2.90A/B/C/D1-604[»]
    3HS5X-ray2.10A/B20-604[»]
    3HS6X-ray2.40A/B20-604[»]
    3HS7X-ray2.65A/B20-604[»]
    3KRKX-ray2.40A/B20-604[»]
    3LN0X-ray2.20A/B/C/D18-604[»]
    3LN1X-ray2.40A/B/C/D18-604[»]
    3MDLX-ray2.20A/B20-599[»]
    3MQEX-ray2.80A/B/C/D18-604[»]
    3NT1X-ray1.73A/B18-604[»]
    3NTBX-ray2.27A/B/C/D18-604[»]
    3NTGX-ray2.19A/B/C/D18-569[»]
    3OLTX-ray2.45A/B20-604[»]
    3OLUX-ray2.35A/B20-604[»]
    3PGHX-ray2.50A/B/C/D18-604[»]
    3Q7DX-ray2.40A/B18-604[»]
    3QH0X-ray2.10A/B1-604[»]
    3QMOX-ray3.00A/B1-604[»]
    3RR3X-ray2.84A/B/C/D18-577[»]
    3TZIX-ray2.15A/B20-604[»]
    4COXX-ray2.90A/B/C/D18-604[»]
    4E1GX-ray2.10A/B1-604[»]
    4FM5X-ray2.81A/B/C/D1-604[»]
    4M10X-ray2.01A/B/C/D18-604[»]
    4M11X-ray2.45A/B/C/D18-569[»]
    4OTYX-ray2.35A/B18-604[»]
    5COXX-ray3.00A/B/C/D18-604[»]
    6COXX-ray2.80A/B18-604[»]
    ProteinModelPortaliQ05769.
    SMRiQ05769. Positions 18-569.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ05769.

    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.
    GeneTreeiENSGT00390000010743.
    HOGENOMiHOG000013149.
    HOVERGENiHBG000366.
    InParanoidiQ05769.
    KOiK11987.
    OMAiICNNVKG.
    OrthoDBiEOG7RFTHC.
    PhylomeDBiQ05769.
    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.
    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.

    Q05769-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLFRAVLLCA ALGLSQAANP CCSNPCQNRG ECMSTGFDQY KCDCTRTGFY    50
    GENCTTPEFL TRIKLLLKPT PNTVHYILTH FKGVWNIVNN IPFLRSLIMK 100
    YVLTSRSYLI DSPPTYNVHY GYKSWEAFSN LSYYTRALPP VADDCPTPMG 150
    VKGNKELPDS KEVLEKVLLR REFIPDPQGS NMMFAFFAQH FTHQFFKTDH 200
    KRGPGFTRGL GHGVDLNHIY GETLDRQHKL RLFKDGKLKY QVIGGEVYPP 250
    TVKDTQVEMI YPPHIPENLQ FAVGQEVFGL VPGLMMYATI WLREHNRVCD 300
    ILKQEHPEWG DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE 350
    LLFNQQFQYQ NRIASEFNTL YHWHPLLPDT FNIEDQEYSF KQFLYNNSIL 400
    LEHGLTQFVE SFTRQIAGRV AGGRNVPIAV QAVAKASIDQ SREMKYQSLN 450
    EYRKRFSLKP YTSFEELTGE KEMAAELKAL YSDIDVMELY PALLVEKPRP 500
    DAIFGETMVE LGAPFSLKGL MGNPICSPQY WKPSTFGGEV GFKIINTASI 550
    QSLICNNVKG CPFTSFNVQD PQPTKTATIN ASASHSRLDD INPTVLIKRR 600
    STEL 604
    Length:604
    Mass (Da):69,013
    Last modified:June 1, 1994 - v1
    Checksum:iDFE1658295C92064
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti98 – 981I → T in AAA39924. (PubMed:1712772)Curated
    Sequence conflicti142 – 1421A → R in AAA39918. (PubMed:1419907)Curated
    Sequence conflicti301 – 3011I → L no nucleotide entry (PubMed:1744122)Curated
    Sequence conflicti585 – 5851H → R in AAA39918. (PubMed:1419907)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M64291 mRNA. Translation: AAA39924.1.
    M94967 mRNA. Translation: AAA39918.1.
    M82866
    , M82862, M82863, M82864, M82865 Genomic DNA. Translation: AAA40448.1.
    M88242 mRNA. Translation: AAA37740.1.
    AK049923 mRNA. Translation: BAC33986.1.
    AK144956 mRNA. Translation: BAE26154.1.
    AK166221 mRNA. Translation: BAE38639.1.
    AK172161 mRNA. Translation: BAE42855.1.
    CH466520 Genomic DNA. Translation: EDL39487.1.
    CCDSiCCDS15353.1.
    PIRiA49010.
    RefSeqiNP_035328.2. NM_011198.3.
    UniGeneiMm.292547.

    Genome annotation databases

    EnsembliENSMUST00000035065; ENSMUSP00000035065; ENSMUSG00000032487.
    GeneIDi19225.
    KEGGimmu:19225.
    UCSCiuc007cxv.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M64291 mRNA. Translation: AAA39924.1 .
    M94967 mRNA. Translation: AAA39918.1 .
    M82866
    , M82862 , M82863 , M82864 , M82865 Genomic DNA. Translation: AAA40448.1 .
    M88242 mRNA. Translation: AAA37740.1 .
    AK049923 mRNA. Translation: BAC33986.1 .
    AK144956 mRNA. Translation: BAE26154.1 .
    AK166221 mRNA. Translation: BAE38639.1 .
    AK172161 mRNA. Translation: BAE42855.1 .
    CH466520 Genomic DNA. Translation: EDL39487.1 .
    CCDSi CCDS15353.1.
    PIRi A49010.
    RefSeqi NP_035328.2. NM_011198.3.
    UniGenei Mm.292547.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1CVU X-ray 2.40 A/B 18-569 [» ]
    1CX2 X-ray 3.00 A/B/C/D 18-604 [» ]
    1DCX model - A/B 18-569 [» ]
    1DD0 model - A/B 18-569 [» ]
    1DDX X-ray 3.00 A/B/C/D 18-569 [» ]
    1PXX X-ray 2.90 A/B/C/D 1-604 [» ]
    3HS5 X-ray 2.10 A/B 20-604 [» ]
    3HS6 X-ray 2.40 A/B 20-604 [» ]
    3HS7 X-ray 2.65 A/B 20-604 [» ]
    3KRK X-ray 2.40 A/B 20-604 [» ]
    3LN0 X-ray 2.20 A/B/C/D 18-604 [» ]
    3LN1 X-ray 2.40 A/B/C/D 18-604 [» ]
    3MDL X-ray 2.20 A/B 20-599 [» ]
    3MQE X-ray 2.80 A/B/C/D 18-604 [» ]
    3NT1 X-ray 1.73 A/B 18-604 [» ]
    3NTB X-ray 2.27 A/B/C/D 18-604 [» ]
    3NTG X-ray 2.19 A/B/C/D 18-569 [» ]
    3OLT X-ray 2.45 A/B 20-604 [» ]
    3OLU X-ray 2.35 A/B 20-604 [» ]
    3PGH X-ray 2.50 A/B/C/D 18-604 [» ]
    3Q7D X-ray 2.40 A/B 18-604 [» ]
    3QH0 X-ray 2.10 A/B 1-604 [» ]
    3QMO X-ray 3.00 A/B 1-604 [» ]
    3RR3 X-ray 2.84 A/B/C/D 18-577 [» ]
    3TZI X-ray 2.15 A/B 20-604 [» ]
    4COX X-ray 2.90 A/B/C/D 18-604 [» ]
    4E1G X-ray 2.10 A/B 1-604 [» ]
    4FM5 X-ray 2.81 A/B/C/D 1-604 [» ]
    4M10 X-ray 2.01 A/B/C/D 18-604 [» ]
    4M11 X-ray 2.45 A/B/C/D 18-569 [» ]
    4OTY X-ray 2.35 A/B 18-604 [» ]
    5COX X-ray 3.00 A/B/C/D 18-604 [» ]
    6COX X-ray 2.80 A/B 18-604 [» ]
    ProteinModelPortali Q05769.
    SMRi Q05769. Positions 18-569.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202463. 5 interactions.
    DIPi DIP-31082N.
    IntActi Q05769. 1 interaction.

    Chemistry

    BindingDBi Q05769.
    ChEMBLi CHEMBL4321.

    Protein family/group databases

    PeroxiBasei 3360. MmPGHS02.

    PTM databases

    PhosphoSitei Q05769.
    UniCarbKBi Q05769.

    Proteomic databases

    PaxDbi Q05769.
    PRIDEi Q05769.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000035065 ; ENSMUSP00000035065 ; ENSMUSG00000032487 .
    GeneIDi 19225.
    KEGGi mmu:19225.
    UCSCi uc007cxv.1. mouse.

    Organism-specific databases

    CTDi 5743.
    MGIi MGI:97798. Ptgs2.

    Phylogenomic databases

    eggNOGi NOG39991.
    GeneTreei ENSGT00390000010743.
    HOGENOMi HOG000013149.
    HOVERGENi HBG000366.
    InParanoidi Q05769.
    KOi K11987.
    OMAi ICNNVKG.
    OrthoDBi EOG7RFTHC.
    PhylomeDBi Q05769.
    TreeFami TF329675.

    Enzyme and pathway databases

    UniPathwayi UPA00662 .
    Reactomei REACT_188623. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    REACT_196559. Synthesis of 15-eicosatetraenoic acid derivatives.

    Miscellaneous databases

    EvolutionaryTracei Q05769.
    NextBioi 296012.
    PROi Q05769.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q05769.
    CleanExi MM_PTGS2.
    Genevestigatori Q05769.

    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.
    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. "TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue."
      Kujubu D.A., Fletcher B.S., Varnum B.C., Lim R.W., Herschman H.R.
      J. Biol. Chem. 266:12866-12872(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Swiss.
    2. "Structure of the mitogen-inducible TIS10 gene and demonstration that the TIS10-encoded protein is a functional prostaglandin G/H synthase."
      Fletcher B.S., Kujubu D.A., Perrin D.M., Herschman H.R.
      J. Biol. Chem. 267:4338-4344(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "Identification of an immediate early gene, pghs-B, whose protein product has prostaglandin synthase/cyclooxygenase activity."
      Ryseck R.-P., Raynoschek C., Macdonald-Bravo H., Dorfman K., Mattei M.-G., Bravo R.
      Cell Growth Differ. 3:443-450(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase."
      O'Banion M.K., Winn V.D., Young D.A.
      Proc. Natl. Acad. Sci. U.S.A. 89:4888-4892(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    5. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J and NOD.
      Tissue: Hippocampus, Mammary gland and Spleen.
    6. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein."
      O'Banion M.K., Sadowski H.B., Winn V., Young D.A.
      J. Biol. Chem. 266:23261-23267(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 281-360.
    8. "The mouse macrophage activation-associated marker protein, p71/73, is an inducible prostaglandin endoperoxide synthase (cyclooxygenase)."
      Phillips T.A., Kujubu D.A., Mackay R.J., Herschman H.R., Russell S.W., Pace J.L.
      J. Leukoc. Biol. 53:411-419(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL PROTEIN SEQUENCE.
    9. "N-glycosylation of prostaglandin endoperoxide synthases-1 and -2 and their orientations in the endoplasmic reticulum."
      Otto J.C., Dewitt D.L., Smith W.L.
      J. Biol. Chem. 268:18234-18242(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-53; ASN-130; ASN-396 AND ASN-580, ABSENCE OF GLYCOSYLATION AT ASN-592.
    10. "Igf2bp1 is required for full induction of Ptgs2 mRNA in colonic mesenchymal stem cells in mice."
      Manieri N.A., Drylewicz M.R., Miyoshi H., Stappenbeck T.S.
      Gastroenterology 143:110-121(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN INTESTINAL WOUND REPAIR, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
    11. "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.
    12. "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.
    13. Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH (S)-FLURBIPROFEN; INDOMETHACIN; HEME AND 1-PHENYLSULFONAMIDE-3-TRIFLUOROMETHYL-5-PARABROMOPHENYLPYRAZOLE, COFACTOR, GLYCOSYLATION AT ASN-53; ASN-130 AND ASN-396.
    14. Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 18-569 IN COMPLEX WITH ARACHIDONIC ACID, GLYCOSYLATION AT ASN-53; ASN-130 AND ASN-396.
    15. "A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385."
      Rowlinson S.W., Kiefer J.R., Prusakiewicz J.J., Pawlitz J.L., Kozak K.R., Kalgutkar A.S., Stallings W.C., Kurumbail R.G., Marnett L.J.
      J. Biol. Chem. 278:45763-45769(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH HEME AND DICLOFENAC, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, DISULFIDE BONDS, ENZYME REGULATION, GLYCOSYLATION AT ASN-53; ASN-130 AND ASN-396.
    16. "Structural basis of fatty acid substrate binding to cyclooxygenase-2."
      Vecchio A.J., Simmons D.M., Malkowski M.G.
      J. Biol. Chem. 285:22152-22163(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 20-604 IN COMPLEX WITH HEME; ACRYLIC ACID; ARACHIDONIC ACID AND DOCOSAHEXAENOIC ACID, CATALYTIC ACTIVITY, ACTIVE SITE, SUBUNIT, COFACTOR, FUNCTION, DISULFIDE BONDS, MUTAGENESIS OF LEU-517 AND ASN-580, GLYCOSYLATION AT ASN-53; ASN-130; ASN-396 AND ASN-580.
    17. "Molecular basis for cyclooxygenase inhibition by the non-steroidal anti-inflammatory drug naproxen."
      Duggan K.C., Walters M.J., Musee J., Harp J.M., Kiefer J.R., Oates J.A., Marnett L.J.
      J. Biol. Chem. 285:34950-34959(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) OF 18-604 IN COMPLEXES WITH HEME AND NAPROXEN ANALOGS, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-53; ASN-130 AND ASN-396.
    18. "The structural basis of endocannabinoid oxygenation by cyclooxygenase-2."
      Vecchio A.J., Malkowski M.G.
      J. Biol. Chem. 286:20736-20745(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 20-599 IN COMPLEX WITH HEME; ACRYLIC ACID AND ARACHIDONIC ACID, FUNCTION, CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-53; ASN-130 AND ASN-396.

    Entry informationi

    Entry nameiPGH2_MOUSE
    AccessioniPrimary (citable) accession number: Q05769
    Secondary accession number(s): Q543K3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: June 1, 1994
    Last modified: October 1, 2014
    This is version 160 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

    3D-structure, Complete proteome, Direct protein sequencing, 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3