PTGS2 (prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase))

2007-05-01   Panagiotis A Konstantinopoulos  , Michalis V Karamouzis  , Athanasios G Papavassiliou  

Department of Biological Chemistry, Medical School, University of Athens, GR-11527 Goudi-Athens, Greece (AGP).

Identity

HGNC
PTGS2
LOCATION
1q31.1
LOCUSID
5743
ALIAS
COX-2,COX2,GRIPGHS,PGG/HS,PGHS-2,PHS-2,hCox-2

DNA/RNA

Description

8633 bases, 10 Exons.

Transcription

One transcript (chr1:184907546-184916179). COX2 promoter is regulated via the interplay between two opposite beta isoforms of the CCAAT/enhancer binding protein and the p300 coactivator.

Proteins

Description

COX2 is an enzyme that belongs to the prostaglandin G/H synthase family. It consists of 604 amino acids and has a molecular weight of 68996Da.
COX2 possesses two catalytic activities and respective active sites:
  • a cyclooxygenase (COX) that converts arachidonic acid to a prostaglandin endoperoxide, prostaglandin G2 (PGG2), and
  • a peroxidase (POX) that reduces PGG2 to PGH2.
    COX2 functions as homodimer although each subunit has both a POX and a COX active site.
    Each subunit binds one heme B (iron-protoporphyrin IX) group.

    • Expression

    Wide expression in alimentary system (esophagus, pharynx), male reproductive system (prostate, seminal vesicles, ejaculatory duct), female reproductive system (cervix, uterus), hematopoietic system (bone marrow, monocytes).

    Localisation

    Intracellular, cytoplasm, microsome, microsomal membrane.

    Function

    Enzyme that functions both as a dioxygenase and as a peroxidase. COX-2 catalyzes the transformation of arachidonic acid to prostaglandin H2, which is the rate-limiting step in the formation of prostaglandins (PGs) and thromboxane A2 (TXA2). COX-2 is a potent mediator of inflammation and is implicated in prostanoid signaling in activity dependent plasticity. It is an inducible enzyme that plays an important role in several pathophysiological processes, including inflammation, angiogenesis, and tumorigenesis.

    Mutations

    Note

    Five heterozygous mutations (1 missense/nonsense, 1 splicing, 3 regulatory) have been identified. Two were associated with diabetes mellitus type 2, one with bladder cancer risk, one with increased risk of colorectal cancer and one with decreased risk of colorectal cancer.

    Implicated in

    Entity name
    Colorectal Cancers
    Disease
    COX2 is involved in regulation of apoptosis, proliferation and invasiveness of colorectal tumor cells and promotes angiogenesis in several animal colon cancer models. It is also implicated in several premalignant lesions including adenomatous polyps. COX2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor, EP2.
    Entity name
    Gastric Cancer
    Disease
    Expression of COX2 is elevated in gastric adenocarcinomas, which correlates with several clinicopathological parameters, including depth of invasion and lymph node metastasis.
    Entity name
    Non small cell lung cancer
    Disease
    Non-small-cell lung cancer (NSCLC), especially adenocarcinomas, overexpress COX2, which contributes to the progression of malignancy by several mechanisms.
    Entity name
    Cholangiocarcinoma
    Disease
    COX2 has been implicated in cholangiocarcinogenesis. Selective COX-2 inhibitors have been shown to inhibit cholangiocarcinoma cell growth in vitro and in animal models.
    Entity name
    Uterine Carcinosarcoma
    Disease
    COX2 is overexpressed in one-third of uterine carcinosarcomas. COX-2 expression is a strong indicator of unfavorable prognosis.
    Entity name
    Head and Neck squamous cell cancer
    Disease
    COX2 is overexpressed in a variety of premalignant and malignant conditions, including oral leukoplakia and squamous cell carcinoma of the head and neck.
    Entity name
    Ovarian cancer
    Disease
    COX-2 is increased in epithelial ovarian cancer and PGE2-synthesis and signalling are important for malignant transformation and progression.
    Entity name
    Pancreatic cancer
    Disease
    Mounting evidence suggests that COX2 is implicated in pancreatic cancer.
    Immunohistochemical, RT-PCR, and Western blotting studies have shown that COX2, is upregulated in human pancreatic cancer cell lines as well as human pancreatic cancer tissues compared with normal ductal cells and normal pancreas specimens. COX2 inhibitors significantly inhibit pancreatic cancer growth both in vitro and in vivo while simultaneously induce apoptosis.
    Entity name
    Other Malignant Diseases
    Disease
    Similar to above tumors, COX2 is implicated in carcinogenesis of multiple tumors including transitional cell bladder cancer, prostate cancer, uterine cancer, cervical cancer, angiosarcoma, hepatocellular cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, thyroid cancer, Wilms tumor.
    Entity name
    Primary Dysmenorrhea
    Disease
    In vivo studies have demonstrated that selective COX-2 inhibitors are effective in treatment of primary dysmenorrhea in women.
    Entity name
    Inflammatory Conditions
    Disease
    COX2 occupies an important in several inflammatory diseases such as osteoarthritis and rheumatoid arthritis.
    Entity name
    Neurolomuscular Disorders
    Disease
    COX2 is implicated in encephalitis, cerebral infarction, polyneuropathy and muscular dystrophies.
    Entity name
    Cardiovascular toxicity and thromboembolic Discorders
    Note
    Selective inhibition of COX2 (without concomitant inhibition of COX1) is associated with significant cardiovascular risk and thromboembolic phenomena.
    Entity name
    Retinopathy
    Disease
    COX2 plays an important role in ischemic proliferative retinopathy, as in the case of diabetic retinopathy.

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    165060212007NF-kappaB/PPAR gamma and/or AP-1/PPAR gamma 'on/off' switches and induction of CBP in colon adenocarcinomas: correlation with COX-2 expression.Konstantinopoulos PA et al
    122038062002Cyclooxygenase-2: a novel molecular target for the prevention and treatment of head and neck cancer.Lin DT et al
    149670782004Cyclooxygenase-2 inhibitors in lung cancer.Ramalingam S et al
    171076252006Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression.Rask K et al
    155895952005COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?Raspollini MR et al
    146165422003Cyclooxygenase-2 and gastric carcinogenesis.Saukkonen K et al
    159218582005Cyclooxygenase-2 and prostaglandin signaling in cholangiocarcinoma.Wu T et al
    153746272004Cyclooxygenases in cancer: progress and perspective.Zha S et al
    117419382002Dynamic regulation of cyclooxygenase-2 promoter activity by isoforms of CCAAT/enhancer-binding proteins.Zhu Y et al

    Other Information

    Locus ID:

    NCBI: 5743
    MIM: 600262
    HGNC: 9605
    Ensembl: ENSG00000073756

    Variants:

    dbSNP: 5743
    ClinVar: 5743
    TCGA: ENSG00000073756
    COSMIC: PTGS2

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000073756ENST00000367468P35354
    ENSG00000073756ENST00000559627Q6ZYK7

    Expression (GTEx)

    0
    5
    10
    15
    20
    25
    Adipose - Subcutaneous
    Adipose - Visceral
    Adrenal Gland
    Artery - Aorta
    Artery - Tibial
    Bladder
    Brain - Amygdala
    Brain - Anterior cingulate cortex
    Brain - Caudate
    Brain - Cerebellar Hemisphere
    Brain - Cerebellum
    Brain - Cortex
    Brain - Frontal Cortex
    Brain - Hippocampus
    Brain - Hypothalamus
    Brain - Nucleus accumbens
    Brain - Putamen
    Brain - Spinal cord
    Brain - Substantia nigra
    Breast - Mammary Tissue
    Cells - Cultured fibroblasts
    Cells - EBV - transformed lymphocytes
    Cervix - Ectocervix
    Cervix - Endocervix
    Colon - Sigmoid
    Colon - Transverse
    Esophagus - Gastroesophageal Junction
    Esophagus - Mucosa
    Esophagus - Muscularis
    Fallopian Tube
    Heart - Atrial Appendage
    Heart - Left Ventricle
    Kidney - Cortex
    Kidney - Medulla
    Liver
    Lung
    Minor Salivary Gland
    Muscle - Skeletal
    Nerve - Tibial
    Ovary
    Pancreas
    Pituitary
    Prostate
    Skin - Not Sun Exposed
    Skin - Sun Exposed
    Small Intestine - Terminal Ileum
    Spleen
    Stomach
    Testis
    Thyroid
    Uterus
    Vagina
    Whole Blood

    Pathways

    PathwaySourceExternal ID
    Arachidonic acid metabolismKEGGko00590
    VEGF signaling pathwayKEGGko04370
    Small cell lung cancerKEGGko05222
    Arachidonic acid metabolismKEGGhsa00590
    VEGF signaling pathwayKEGGhsa04370
    Pathways in cancerKEGGhsa05200
    Small cell lung cancerKEGGhsa05222
    Metabolic pathwaysKEGGhsa01100
    LeishmaniasisKEGGko05140
    LeishmaniasisKEGGhsa05140
    Serotonergic synapseKEGGhsa04726
    Retrograde endocannabinoid signalingKEGGhsa04723
    Retrograde endocannabinoid signalingKEGGko04723
    NF-kappa B signaling pathwayKEGGhsa04064
    NF-kappa B signaling pathwayKEGGko04064
    Chemical carcinogenesisKEGGhsa05204
    Chemical carcinogenesisKEGGko05204
    Ovarian steroidogenesisKEGGhsa04913
    Ovarian steroidogenesisKEGGko04913
    TNF signaling pathwayKEGGhsa04668
    TNF signaling pathwayKEGGko04668
    MicroRNAs in cancerKEGGhsa05206
    MicroRNAs in cancerKEGGko05206
    Oxytocin signaling pathwayKEGGhsa04921
    Oxytocin signaling pathwayKEGGko04921
    Regulation of lipolysis in adipocytesKEGGhsa04923
    Immune SystemREACTOMER-HSA-168256
    Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
    Signaling by InterleukinsREACTOMER-HSA-449147
    MetabolismREACTOMER-HSA-1430728
    Metabolism of lipids and lipoproteinsREACTOMER-HSA-556833
    Arachidonic acid metabolismREACTOMER-HSA-2142753
    Synthesis of Prostaglandins (PG) and Thromboxanes (TX)REACTOMER-HSA-2162123
    Synthesis of 15-eicosatetraenoic acid derivativesREACTOMER-HSA-2142770
    Metabolism of vitamins and cofactorsREACTOMER-HSA-196854
    Metabolism of water-soluble vitamins and cofactorsREACTOMER-HSA-196849
    Nicotinate metabolismREACTOMER-HSA-196807
    Nicotinamide salvagingREACTOMER-HSA-197264
    Interleukin-4 and 13 signalingREACTOMER-HSA-6785807
    Interleukin-10 signalingREACTOMER-HSA-6783783
    IL-17 signaling pathwayKEGGko04657
    IL-17 signaling pathwayKEGGhsa04657

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High
    cerebral cortex
    cerebellum
    hippocampus
    caudate
    thyroid gland
    adrenal gland
    bronchus
    lung
    oral mucosa
    salivary gland
    esophagus
    stomach 1
    stomach 2
    duodenum
    small intestine
    rectum
    liver
    gallbladder
    pancreas
    kidney
    urinary bladder
    testis
    epididymis
    seminal vesicle
    prostate
    vagina
    ovary
    fallopian tube
    endometrium 1
    endometrium 2
    cervix, uterine
    placenta
    heart muscle
    smooth muscle
    skeletal muscle
    soft tissue 1
    soft tissue 2
    adipose tissue
    skin 1
    skin 2
    appendix
    spleen
    lymph node
    tonsil
    bone marrow

    PharmGKB

    Entity IDNameTypeEvidenceAssociationPKPDPMIDs
    PA10226valdecoxibChemicalVipGeneassociated19602986
    PA10384antiinflammatory and antirheumatic products, non-steroidsChemicalPathwayassociated22336956
    PA131285527oxaliplatinChemicalClinicalAnnotationassociatedPD19219602
    PA137179528nimesulideChemicalVariantAnnotationassociatedPK
    PA164712462Antiinflammatory agents, non-steroidsChemicalMultilinkAnnotation, VipGeneassociated19602986, 25876828
    PA164712669CoxibsChemicalVipGeneassociated19602986
    PA164769031lumiracoxibChemicalVipGeneassociated19602986
    PA164776853etoricoxibChemicalVipGeneassociated19602986
    PA166153552rs5275VariantVipGeneassociated17066444, 17573729, 18085997, 18989535, 19748095, 16678543
    PA166153559rs20417VariantVipGeneassociated12920574, 14754878, 15138244, 15316498, 15544595, 15604423, 15767339, 16083713, 16401468, 16678543, 17178263, 17350020, 17578436, 17631383, 18085997, 18489027, 19056642, 19468846, 19488068, 19625268, 20033767, 20299798, 12377741
    PA166153585rs689466VariantVipGeneassociated15167446, 16083713, 18085997, 18489027, 19422084, 12920574
    PA443635Cardiovascular DiseasesDiseaseVipGeneassociated
    PA443796Coronary Artery DiseaseDiseaseClinicalAnnotationassociatedPD
    PA443797Coronary DiseaseDiseaseVipGeneassociated
    PA444552HypertensionDiseaseClinicalAnnotationassociatedPD
    PA445019Myocardial InfarctionDiseaseVipGeneassociated
    PA445062NeoplasmsDiseaseVipGeneassociated11857443
    PA445425Prostatic NeoplasmsDiseaseClinicalAnnotationassociatedPD
    PA446108Colorectal NeoplasmsDiseaseClinicalAnnotationassociatedPD19219602
    PA447054StrokeDiseaseVipGeneassociated
    PA448497aspirinChemicalClinicalAnnotationassociatedPD
    PA448499atenololChemicalClinicalAnnotationassociatedPD
    PA448771capecitabineChemicalClinicalAnnotationassociatedPD19219602
    PA448871celecoxibChemicalPathway, VipGeneassociated19602986, 22336956
    PA449293diclofenacChemicalVipGeneassociated19602986
    PA449550etodolacChemicalVipGeneassociated19602986
    PA449957ibuprofenChemicalClinicalAnnotation, Pathway, VipGeneassociatedPD16678543, 19602986, 25502615
    PA449982indomethacinChemicalVipGeneassociated19602986
    PA450353meloxicamChemicalVipGeneassociated19602986
    PA450595naproxenChemicalVipGeneassociated19602986
    PA451268rofecoxibChemicalClinicalAnnotation, VipGeneassociatedPD16678543, 19602986

    References

    Pubmed IDYearTitleCitations
    382893942024Mutation of the cyclooxygenase 2 gene promoter and anastomotic leakage in colorectal cancer patients: retrospective cohort study.0
    383346502024Involvement of Cyclooxygenase-2 in Establishing an Immunosuppressive Microenvironment in Tumorspheres Derived from TMZ-Resistant Glioblastoma Cell Lines and Primary Cultures.0
    384266192024Expression of PTGS2 along with genes regulating VEGF signalling pathway and association with high-risk factors in locally advanced oral squamous cell carcinoma.2
    385246342024Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis.2
    385553912024The cyclooxygenase-2 upregulation mediates production of PGE2 autacoid to positively regulate interleukin-6 secretion in chronic rhinosinusitis with nasal polyps and polyp-derived fibroblasts.0
    385830312024[The relationship between the expression of PGE2 and COX-2 and the osteogenic activity and oxygen level of alveolar bone].0
    386124782024Rel Family Transcription Factor NFAT5 Upregulates COX2 via HIF-1α Activity in Ishikawa and HEC1a Cells.0
    387780472024RUNX1-induced upregulation of PTGS2 enhances cell growth, migration and invasion in colorectal cancer cells.0
    389673642024Breast volume in non-obese females is related to breast adipose cell hypertrophy, inflammation, and COX2 expression.0
    382893942024Mutation of the cyclooxygenase 2 gene promoter and anastomotic leakage in colorectal cancer patients: retrospective cohort study.0
    383346502024Involvement of Cyclooxygenase-2 in Establishing an Immunosuppressive Microenvironment in Tumorspheres Derived from TMZ-Resistant Glioblastoma Cell Lines and Primary Cultures.0
    384266192024Expression of PTGS2 along with genes regulating VEGF signalling pathway and association with high-risk factors in locally advanced oral squamous cell carcinoma.2
    385246342024Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis.2
    385553912024The cyclooxygenase-2 upregulation mediates production of PGE2 autacoid to positively regulate interleukin-6 secretion in chronic rhinosinusitis with nasal polyps and polyp-derived fibroblasts.0
    385830312024[The relationship between the expression of PGE2 and COX-2 and the osteogenic activity and oxygen level of alveolar bone].0

    Citation

    Panagiotis A Konstantinopoulos ; Michalis V Karamouzis ; Athanasios G Papavassiliou

    PTGS2 (prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase))

    Atlas Genet Cytogenet Oncol Haematol. 2007-05-01

    Online version: http://atlasgeneticsoncology.org/gene/509/ptgs2