MPGES-2

Microsomal prostaglandin E synthase-2 (mPGES-2)^[5][6] or Prostaglandin E synthase 2 is an enzyme that in humans encoded by the PTGES2 gene located on chromosome 9.^[7][8] The protein encoded by this gene is a membrane-associated prostaglandin E synthase, which catalyzes the conversion of prostaglandin H2 to prostaglandin E2. This protein also has been shown to activate the transcription regulated by a gamma-interferon-activated transcription element (GATE). Multiple transcript variants have been found for this gene.^[9]

PTGES2
Identifiers
Aliases	PTGES2, C9orf15, GBF-1, GBF1, PGES2, mPGES-2, prostaglandin E synthase 2
External IDs	OMIM: 608152; MGI: 1917592; HomoloGene: 11819; GeneCards: PTGES2; OMA:PTGES2 - orthologs
EC number	5.3.99.3
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q34.11 Start 128,120,693 bp[1] End 128,128,462 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 B Start 32,285,908 bp[2] End 32,295,784 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart gastrocnemius muscle mucosa of transverse colon left ventricle right auricle of heart right frontal lobe prefrontal cortex anterior cingulate cortex muscle of thigh left adrenal gland Top expressed in right kidney muscle of thigh proximal tubule brown adipose tissue granulocyte neural layer of retina soleus muscle masseter muscle dentate gyrus of hippocampal formation granule cell interventricular septum More reference expression data BioGPS n/a
Gene ontology Molecular function protein-disulfide reductase activity DNA binding glutathione binding isomerase activity protein binding heme binding lyase activity electron transfer activity prostaglandin-E synthase activity Cellular component cytoplasm integral component of membrane Golgi apparatus membrane Golgi membrane mitochondrion perinuclear region of cytoplasm nucleus extracellular region cytosol azurophil granule lumen Biological process prostaglandin metabolic process lipid metabolism cell redox homeostasis fatty acid metabolic process secretion positive regulation of transcription, DNA-templated fatty acid biosynthetic process prostaglandin biosynthetic process cyclooxygenase pathway neutrophil degranulation electron transport chain Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 80142 96979 Ensembl ENSG00000148334 ENSMUSG00000026820 UniProt Q9H7Z7 Q8BWM0 RefSeq (mRNA) NM_001256335 NM_025072 NM_198938 NM_198939 NM_198940 NM_133783 RefSeq (protein) NP_001243264 NP_079348 NP_945176 NP_598544 Location (UCSC) Chr 9: 128.12 – 128.13 Mb Chr 2: 32.29 – 32.3 Mb PubMed search [3] [4]
Wikidata
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Structure

Microsomal prostaglandin E synthase type-2 (mPTGES2) has been crystallized with an anti-inflammatory drug indomethacin (IMN).^[10] The N-terminal of mPTGES2 is attached to the lipid membrane and the two hydrophobic pockets connected to form a V shape are located in the bottom of a large cavity for IMN binding. The mPTGES2 exists in a dimer.^[10]

Function

The gene encoding the PTGES2 protein contains 10 exons. The PTGE2 protein encoded by the gene is a 33-kDa membrane-associated ^[11] prostaglandin E synthase that is thought to be targeted to the Golgi apparatus as well as the mitochondrion within the cell. Prostaglandin E synthase catalyzes the conversion of prostaglandin H2 to prostaglandin E2. The particular reaction catalyzed by PTGE2 is thought to be:

(5Z,13E)-(15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate.^[12]

The PTGE2 protein functions in part of the prostaglandin synthesis pathway, which forms a component of the overall lipid synthesis mechanism in the human body. The activity of PTGES2 is thought to be increased in the presence of sulfhydryl compounds, in particular dithiothreitol.^[13]

The PTGE2 protein also has been shown to activate the transcription regulated by an interferon-gamma gamma-interferon-activated transcription element (GATE).^[8]

Clinical significance

The excess production of prostaglandin E 2 is known to contribute to inflammatory diseases which includes rheumatoid arthritis, atherosclerosis, and cancer.^[14][15] Furthermore, naturally occurring polymorphisms of PTGES2 have been shown to be associated with increased risks for diabetes mellitus and metabolic syndromes.^[16][17]

As such, pharmacological inhibition of prostaglandin E 2 production by synthetic minor prenylated chalcones and flavonoids has potential therapeutic viability.^[14] It has been shown that the synthesis of prostaglandin E 2 in the endothelial cells of the brain is important for inflammation-induced fever.^[18] Additionally, investigators have observed elevations in cell doubling rates for several cancer cell types in the presence of prostaglandin E 2 –producing cell lines.^[19]