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P35354

- PGH2_HUMAN

UniProt

P35354 - PGH2_HUMAN

Protein

Prostaglandin G/H synthase 2

Gene

PTGS2

Organism
Homo sapiens (Human)
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 2 (15 Dec 1998)
      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.1 Publication

    Cofactori

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

    Kineticsi

    1. KM=16.2 µM for arachidonate (in absence of sodium nitroprusside NO donor)1 Publication
    2. KM=17.0 µM for arachidonate (in presence of sodium nitroprusside NO donor)1 Publication

    Vmax=81.3 nmol/min/mg enzyme (in absence of sodium nitroprusside NO donor)1 Publication

    Vmax=132 nmol/min/mg enzyme (in absence of sodium nitroprusside NO donor)1 Publication

    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. arachidonate 15-lipoxygenase activity Source: Reactome
    2. enzyme binding Source: UniProtKB
    3. heme binding Source: UniProtKB
    4. lipid binding Source: Ensembl
    5. metal ion binding Source: UniProtKB-KW
    6. peroxidase activity Source: UniProtKB
    7. prostaglandin-endoperoxide synthase activity Source: UniProtKB

    GO - Biological processi

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

    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

    BioCyciMetaCyc:HS01115-MONOMER.
    BRENDAi1.14.99.1. 2681.
    ReactomeiREACT_150149. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    REACT_150422. Synthesis of 15-eicosatetraenoic acid derivatives.
    SABIO-RKP35354.
    UniPathwayiUPA00662.

    Protein family/group databases

    PeroxiBasei3321. HsPGHS02.

    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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:9605. PTGS2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. endoplasmic reticulum membrane Source: Reactome
    3. neuron projection Source: MGI
    4. nucleus Source: UniProtKB
    5. protein complex Source: Ensembl

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi526 – 5261C → S: Prevents activation by nitric oxid (NO). 1 Publication
    Mutagenesisi555 – 5551C → S: Abolishes enzyme activity. 1 Publication
    Mutagenesisi561 – 5611C → S: Does not affect activation by nitric oxid (NO). 1 Publication

    Organism-specific databases

    PharmGKBiPA293.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1717Sequence AnalysisAdd
    BLAST
    Chaini18 – 604587Prostaglandin G/H synthase 2PRO_0000023875Add
    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
    Glycosylationi130 – 1301N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi396 – 3961N-linked (GlcNAc...)Sequence Analysis
    Modified residuei526 – 5261S-nitrosocysteine1 Publication
    Disulfide bondi555 ↔ 561By similarity
    Glycosylationi580 – 5801N-linked (GlcNAc...)1 Publication

    Post-translational modificationi

    S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, S-nitrosylation

    Proteomic databases

    MaxQBiP35354.
    PaxDbiP35354.
    PRIDEiP35354.

    PTM databases

    PhosphoSiteiP35354.

    Expressioni

    Inductioni

    By cytokines and mitogens.

    Gene expression databases

    ArrayExpressiP35354.
    BgeeiP35354.
    CleanExiHS_PTGS2.
    GenevestigatoriP35354.

    Organism-specific databases

    HPAiCAB000113.
    HPA001335.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    BioGridi111715. 27 interactions.
    DIPiDIP-28131N.
    IntActiP35354. 2 interactions.
    MINTiMINT-203337.
    STRINGi9606.ENSP00000356438.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1V0Xmodel-A1-604[»]
    ProteinModelPortaliP35354.
    SMRiP35354. 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.
    InParanoidiP35354.
    KOiK11987.
    OMAiICNNVKG.
    OrthoDBiEOG7RFTHC.
    PhylomeDBiP35354.
    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. 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.

    P35354-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLARALLLCA VLALSHTANP CCSHPCQNRG VCMSVGFDQY KCDCTRTGFY    50
    GENCSTPEFL TRIKLFLKPT PNTVHYILTH FKGFWNVVNN IPFLRNAIMS 100
    YVLTSRSHLI DSPPTYNADY GYKSWEAFSN LSYYTRALPP VPDDCPTPLG 150
    VKGKKQLPDS NEIVEKLLLR RKFIPDPQGS NMMFAFFAQH FTHQFFKTDH 200
    KRGPAFTNGL GHGVDLNHIY GETLARQRKL RLFKDGKMKY QIIDGEMYPP 250
    TVKDTQAEMI YPPQVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD 300
    VLKQEHPEWG DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE 350
    LLFNKQFQYQ NRIAAEFNTL YHWHPLLPDT FQIHDQKYNY QQFIYNNSIL 400
    LEHGITQFVE SFTRQIAGRV AGGRNVPPAV QKVSQASIDQ SRQMKYQSFN 450
    EYRKRFMLKP YESFEELTGE KEMSAELEAL YGDIDAVELY PALLVEKPRP 500
    DAIFGETMVE VGAPFSLKGL MGNVICSPAY WKPSTFGGEV GFQIINTASI 550
    QSLICNNVKG CPFTSFSVPD PELIKTVTIN ASSSRSGLDD INPTVLLKER 600
    STEL 604
    Length:604
    Mass (Da):68,996
    Last modified:December 15, 1998 - v2
    Checksum:i72FBD699F6128519
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti165 – 1651E → G in AAA58433. (PubMed:1380156)Curated
    Sequence conflicti438 – 4381I → T in AAA35803. (PubMed:8473346)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti228 – 2281R → H.1 Publication
    Corresponds to variant rs3218622 [ dbSNP | Ensembl ].
    VAR_016262
    Natural varianti428 – 4281P → A.1 Publication
    Corresponds to variant rs4648279 [ dbSNP | Ensembl ].
    VAR_016263
    Natural varianti488 – 4881E → G.
    Corresponds to variant rs5272 [ dbSNP | Ensembl ].
    VAR_011980
    Natural varianti511 – 5111V → A.2 Publications
    Corresponds to variant rs5273 [ dbSNP | Ensembl ].
    VAR_011981
    Natural varianti587 – 5871G → R.1 Publication
    Corresponds to variant rs3218625 [ dbSNP | Ensembl ].
    VAR_016264

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L15326 mRNA. Translation: AAA35803.1.
    M90100 mRNA. Translation: AAA58433.1.
    D28235 Genomic DNA. Translation: BAA05698.1.
    U04636 Genomic DNA. Translation: AAA57317.1.
    AY462100 mRNA. Translation: AAR23927.1.
    AY229989 Genomic DNA. Translation: AAO38056.1.
    AY382629 Genomic DNA. Translation: AAQ75702.1.
    AK292167 mRNA. Translation: BAF84856.1.
    AL033533 Genomic DNA. Translation: CAB41240.1.
    CH471067 Genomic DNA. Translation: EAW91216.1.
    BC013734 mRNA. Translation: AAH13734.1.
    CCDSiCCDS1371.1.
    PIRiA46150.
    RefSeqiNP_000954.1. NM_000963.3.
    UniGeneiHs.196384.

    Genome annotation databases

    EnsembliENST00000367468; ENSP00000356438; ENSG00000073756.
    GeneIDi5743.
    KEGGihsa:5743.
    UCSCiuc001gsb.3. human.

    Polymorphism databases

    DMDMi3915797.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPs
    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L15326 mRNA. Translation: AAA35803.1 .
    M90100 mRNA. Translation: AAA58433.1 .
    D28235 Genomic DNA. Translation: BAA05698.1 .
    U04636 Genomic DNA. Translation: AAA57317.1 .
    AY462100 mRNA. Translation: AAR23927.1 .
    AY229989 Genomic DNA. Translation: AAO38056.1 .
    AY382629 Genomic DNA. Translation: AAQ75702.1 .
    AK292167 mRNA. Translation: BAF84856.1 .
    AL033533 Genomic DNA. Translation: CAB41240.1 .
    CH471067 Genomic DNA. Translation: EAW91216.1 .
    BC013734 mRNA. Translation: AAH13734.1 .
    CCDSi CCDS1371.1.
    PIRi A46150.
    RefSeqi NP_000954.1. NM_000963.3.
    UniGenei Hs.196384.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1V0X model - A 1-604 [» ]
    ProteinModelPortali P35354.
    SMRi P35354. Positions 18-568.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111715. 27 interactions.
    DIPi DIP-28131N.
    IntActi P35354. 2 interactions.
    MINTi MINT-203337.
    STRINGi 9606.ENSP00000356438.

    Chemistry

    BindingDBi P35354.
    ChEMBLi CHEMBL230.
    DrugBanki DB00316. Acetaminophen.
    DB00945. Aspirin.
    DB01014. Balsalazide.
    DB00963. Bromfenac.
    DB00821. Carprofen.
    DB00482. Celecoxib.
    DB01188. Ciclopirox.
    DB00586. Diclofenac.
    DB00861. Diflunisal.
    DB01240. Epoprostenol.
    DB00749. Etodolac.
    DB01628. Etoricoxib.
    DB00573. Fenoprofen.
    DB00712. Flurbiprofen.
    DB00154. gamma-Homolinolenic acid.
    DB01404. Ginseng.
    DB01050. Ibuprofen.
    DB00159. Icosapent.
    DB00328. Indomethacin.
    DB01009. Ketoprofen.
    DB00465. Ketorolac.
    DB00480. Lenalidomide.
    DB01283. Lumiracoxib.
    DB00939. Meclofenamic acid.
    DB00784. Mefenamic acid.
    DB00814. Meloxicam.
    DB00244. Mesalazine.
    DB00461. Nabumetone.
    DB00788. Naproxen.
    DB00991. Oxaprozin.
    DB00812. Phenylbutazone.
    DB00533. Rofecoxib.
    DB00936. Salicyclic acid.
    DB01399. Salsalate.
    DB00605. Sulindac.
    DB00870. Suprofen.
    DB00469. Tenoxicam.
    DB01041. Thalidomide.
    DB01600. Tiaprofenic acid.
    DB00500. Tolmetin.
    DB00580. Valdecoxib.
    GuidetoPHARMACOLOGYi 1376.

    Protein family/group databases

    PeroxiBasei 3321. HsPGHS02.

    PTM databases

    PhosphoSitei P35354.

    Polymorphism databases

    DMDMi 3915797.

    Proteomic databases

    MaxQBi P35354.
    PaxDbi P35354.
    PRIDEi P35354.

    Protocols and materials databases

    DNASUi 5743.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000367468 ; ENSP00000356438 ; ENSG00000073756 .
    GeneIDi 5743.
    KEGGi hsa:5743.
    UCSCi uc001gsb.3. human.

    Organism-specific databases

    CTDi 5743.
    GeneCardsi GC01M186640.
    HGNCi HGNC:9605. PTGS2.
    HPAi CAB000113.
    HPA001335.
    MIMi 600262. gene.
    neXtProti NX_P35354.
    PharmGKBi PA293.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG39991.
    HOGENOMi HOG000013149.
    HOVERGENi HBG000366.
    InParanoidi P35354.
    KOi K11987.
    OMAi ICNNVKG.
    OrthoDBi EOG7RFTHC.
    PhylomeDBi P35354.
    TreeFami TF329675.

    Enzyme and pathway databases

    UniPathwayi UPA00662 .
    BioCyci MetaCyc:HS01115-MONOMER.
    BRENDAi 1.14.99.1. 2681.
    Reactomei REACT_150149. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
    REACT_150422. Synthesis of 15-eicosatetraenoic acid derivatives.
    SABIO-RK P35354.

    Miscellaneous databases

    GeneWikii Prostaglandin-endoperoxide_synthase_2.
    PTGS2.
    GenomeRNAii 5743.
    NextBioi 22358.
    PROi P35354.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P35354.
    Bgeei P35354.
    CleanExi HS_PTGS2.
    Genevestigatori P35354.

    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 of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines."
      Jones D.A., Carlton D.P., McIntyre T.M., Zimmerman G.A., Prescott S.M.
      J. Biol. Chem. 268:9049-9054(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Endothelial cell.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Endothelial cell.
    3. "Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2."
      Kosaka T., Miyata A., Ihara H., Hara S., Sugimoto T., Takeda O., Takahashi E., Tanabe T.
      Eur. J. Biochem. 221:889-897(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Peripheral blood.
    4. "Structure of the human cyclo-oxygenase-2 gene."
      Appleby S.B., Ristimaki A., Neilson K., Narko K., Hla T.
      Biochem. J. 302:723-727(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Placenta.
    5. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
      Sharma S.V., Aronstam R.S.
      Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Placenta.
    6. NIEHS SNPs program
      Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-228; ALA-428; ALA-511 AND ARG-587.
    7. SeattleSNPs variation discovery resource
      Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    8. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Synovium.
    9. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    10. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    11. "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].
      Tissue: Lung.
    12. "Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system."
      Barnett J., Chow J., Ives D., Chiou M., Mackenzie R., Osen E., Nguyen B., Tsing S., Bach C., Freire J.
      Biochim. Biophys. Acta 1209:130-139(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION.
    13. "Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2."
      Kim S.F., Huri D.A., Snyder S.H.
      Science 310:1966-1970(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, S-NITROSYLATION AT CYS-526, MUTAGENESIS OF CYS-526; CYS-555 AND CYS-561.
    14. "Glycosylation regulates turnover of cyclooxygenase-2."
      Sevigny M.B., Li C.F., Alas M., Hughes-Fulford M.
      FEBS Lett. 580:6533-6536(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-580.
    15. "Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk."
      Goodman J.E., Bowman E.D., Chanock S.J., Alberg A.J., Harris C.C.
      Carcinogenesis 25:2467-2472(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ALA-511.
    16. "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.
    17. "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 nameiPGH2_HUMAN
    AccessioniPrimary (citable) accession number: P35354
    Secondary accession number(s): A8K802, Q16876
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: December 15, 1998
    Last modified: October 1, 2014
    This is version 160 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    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, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

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