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FLASH GENE
Symbol PTGS2 contributors: mct - updated : 25-12-2016
HGNC name prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)
HGNC id 9605
Location 1q31.1      Physical location : 186.640.944 - 186.649.559
Synonym name
  • cyclooxygenase 2
  • prostaglandin G/H synthase and cyclooxygenase
  • PGH synthase 2
  • PHS II
    • Synonym symbol(s) COX2, PGH2, PGHS2, COX-2, GRIPGHS, PGG/HS
    EC.number 1.14.99.1
    DNA
    TYPE functioning gene
    STRUCTURE 8.61 kb     10 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor   HRE
    motif repetitive sequence   other
    text structure
  • 5'-flanking region has shown several potential transcription regulatory sequences, including a TATA box, a C/EBP motif, two AP-2 sites, three SP1 sites, two NF-kappa B sites, a CRE motif and an Ets-1 site (Appleby 1994)
  • three SNP in the promoter
  • regulation of the promoter by an interplay between two opposite beta isoforms of CCAAT/enhancer binding protein and p300 coactivator
  • a Lef1-binding site at the 3 prime region of the genomic locus
  • promoter activity was repressed upon SNAI1 overexpression
    • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 4507 - 604 - PMID: 7945196
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     pharynx   highly
    Reproductivefemale systemuteruscervix highly
     male systemprostate  highly
     male systemseminal vesicles   
     male systemmale genital tractejaculatory duct  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, growth/childhood, puberty
    Text seminal vesicles and ejaculatory ducts,prebubertal period
    PROTEIN
    PHYSICAL PROPERTIES Hydrophobic
    STRUCTURE
    motifs/domains
  • a single eight-stranded continuously hydrogen-bunded antiparallel beta-barrel which encloses an internal ligand binding site
  • one EGF-like domain
    • mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine Ptgs2
    Homologene
    FAMILY
  • Kernel group, lipocalin family
  • prostaglandin G/H synthase family
    • CATEGORY enzyme , protooncogene , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic,microsome
    basic FUNCTION
  • prostaglandin G/H synthase, potent mediator of inflammation and role for prostanoid signaling in activity dependent plasticity
  • oxidoreductase/electron transporter
  • inducible enzyme that plays an important role in several pathophysiological processes, including inflammation, angiogenesis, and tumorigenesis( may be involved in the regulation of angiogenesis in pituitary tumors)
  • playing an important role in ischemic proliferative retinopathy, as in diabetes
  • stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor, EP2
  • catalyzing the crucial step of the production of prostaglandin E2, which is a principal mediator of joint inflammation such as rheumatoid arthritis and osteoarthritis
  • may also play a role in pterygium formation
  • is transcriptionally active before and after labour
  • in cardiomyocytes, influences cardiac rhythm and function
  • with ST6GALNAC5 and HBEGF, are mediators of cancer cell passage through the blood-brain barrier
  • PTGES and PTGS2 are co-localized and act together to exacerbate stroke injury, by excessive PGE(2) production
  • plays an important role in GDF2 induced osteogenic differentiation in mesenchymal stem cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS electron transport
    PATHWAY
    metabolism
    signaling
  • role of the CPSF4/PTGS2 signaling pathway in the regulation of lung cancer growth and progression
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with ADIPOQ and PRKAB1 to protects the heart from ischemia-reperfusion injury
  • interacting with ELAVL1(can stabilize the mRNA of PTGS2, and cytoplasmic expression of ELAVL1 is associated with increased PTGS2 expression in some cancers)
  • negatively regulating STK17B, a serine-threonine kinase implicated in the regulation of apoptosis, suggesting a novel mechanism for the effect of PTGS2 on cancer cell survival
  • VRK2 is an active kinase playing a role in regulation of cancer cell invasion through the NFAT pathway and PTGS2 expression
  • PTGS2 and GDF2 may form an important regulatory loop to orchestrate the osteogenic differentiation in mesenchymal stem cells
  • PTGS2 and and VEGFC are inducers of lymphangiogenesis and their expression levels were correlated in non-Hodgkin lymphoma
  • apoptosis-enhancing effect of FAU-BCL2L14 is due in part to down-regulation of PTGS2 activation in macrophages
  • MAT2A interacts with histone methyltransferase SETDB1 and inhibits PTGS2 gene expression
  • RXRA suppresses PGE2 production through inhibiting NFKB activity and PTGS2 expression
  • CAV1 may be a cofactor in the interaction of DERL1 and PTGS2 and may facilitate DERL1- and VCP complex-mediated PTGS2 ubiquitination, retrotranslocation, and degradation
  • AREG, BTC, and EREG induced prostaglandin E2 (PGE2) production by upregulating PTGS2 expression through ERK1/2 signaling in granulosa cells
  • role for ADRB1 in the downregulation of PTGS2
  • PTH can stimulate a novel negative feedback of its anabolic actions by stimulating TNFSF1l and PTGS2 expression
  • CPSF4 bind to PTGS2 promoter sequences directly and activate the transcription of PTGS2
    • cell & other
    REGULATION
    activated by inducible nitric oxide synthase (NOS2A)
    induced by mitogen and cytokine inducible form
    Other regulated by an endogenous cellular factor
    regulated by LEF1 with CTNN1B in arthritic chondrocytes
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in squamous cell carcinoma of the head and neck, in retinoblastoma, and in cholangiocarcinoma
    tumoral     --over  
    in lung and colon adenocarcinoma, pituitary tumors and mammary tumors, in colorectal adenomas
    tumoral     --over  
    correlated with K-RAS mutation in colorectal adenoma in progression
    constitutional     --over  
    in neurals cell of the myenteric plexus in active inflammatory bowel disease
    constitutional     --over  
    in amyotrophic lateral sclerosis
    tumoral     --over  
    in renal call carcinoma
    constitutional       loss of function
    in cardiomyocytes may contribute to heart failure in patients receiving nonsteroidal anti-inflammatory drugs specific for inhibition of PTGS2
    tumoral     --over  
    in colorectal cancer (CRC), rendering tumour cells resistant to apoptosis
    constitutional     --over  
    in the amnion is critical for the production of prostaglandins that induce labour
    tumoral     --low  
    in squamous cell carcinoma (SCC) (pMID: 23261444)
    tumoral     --over  
    of CPSF4 and PTGS2 proteins predicted poor prognosis of patients with lung cancers
    Susceptibility
  • to type 2 diabetes mellitus in Pima indians
  • to development of prostate cancer
  • to aspirin resistance
    • Variant & Polymorphism SNP , insertion/deletion
  • allele C associated with decreased promoter activity and susceptibility to type 2 diabetes mellitus
  • SNP -297G was associated with a decreased risk for prostate cancer
  • partial deletion of exon 5 associated with aspirin resistance
    • Candidate gene for treatment of amyotrophic lateral sclerosis
    Marker
    Therapy target
    ANIMAL & CELL MODELS