PTGES2

Prostaglandin E synthase 2

PDB rendering based on 1z9h.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PTGES2 ; C9orf15; GBF-1; GBF1; PGES2; mPGES-2
External IDs OMIM: 608152 MGI: 1917592 HomoloGene: 11819 IUPHAR: 1378 ChEMBL: 4411 GeneCards: PTGES2 Gene
EC number 5.3.99.3
Orthologs
Species Human Mouse
Entrez 80142 96979
Ensembl ENSG00000148334 ENSMUSG00000026820
UniProt Q9H7Z7 Q8BWM0
RefSeq (mRNA) NM_001256335 NM_133783
RefSeq (protein) NP_001243264 NP_598544
Location (UCSC) Chr 9:
128.12 – 128.13 Mb		 Chr 2:
32.4 – 32.41 Mb
PubMed search

Prostaglandin E synthase 2 is an enzyme that in humans is encoded by the PTGES2 gene located on chromosome 9.[1][2]

Function

The gene encoding the PTGES2 protein contains 10 exons. The PTGE2 protein encoded by the gene is a 33-kDa membrane-associated [3] 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.[4]

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 sulfhydril coumpounds, in particular dithiothreitol.[5]

The PTGE2 protein also has been shown to activate the transcription regulated by an interferon-gamma gamma-interferon-activated transcription element (GATE).[2]

Model organisms have been used in the study of PTGES2 function. A conditional knockout mouse line, called Ptges2tm1a(EUCOMM)Wtsi[10][11] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty two tests were carried out on mutant mice, but no significant abnormalities were observed.[8]

Clinical significance

The excess production of prostaglandin E 2 is known to contribute to inflammatory diseases which includes rheumatoid arthritis, atherosclerosis, and cancer.[16][17] Furthermore, naturally occurring polymorphisms of PTGES2 have been shown to be associated with increased risks for diabetes mellitus and metabolic syndromes.[18][19]

As such, pharmacological inhibition of prostaglandin E 2 production by synthetic minor prenylated chalcones and flavonoids has potential therapeutic viability.[16] It has been shown that the synthesis of prostaglandin E 2 in the endothelial cells of the brain is important for inflammation-induced fever.[20] Additionally, investigators have observed elevations in cell doubling rates for several cancer cell types in the presence of prostaglandin E 2 –producing cell lines.[21]

References

  1. ↑ Tanikawa N, Ohmiya Y, Ohkubo H, Hashimoto K, Kangawa K, Kojima M, Ito S, Watanabe K (Mar 2002). "Identification and characterization of a novel type of membrane-associated prostaglandin E synthase". Biochemical and Biophysical Research Communications 291 (4): 884–9. doi:10.1006/bbrc.2002.6531. PMID 11866447.
  2. 1 2 "Entrez Gene: prostaglandin E synthase 2".
  3. ↑ Tanikawa N, Ohmiya Y, Ohkubo H, Hashimoto K, Kangawa K, Kojima M, Ito S, Watanabe K (2002). "Identification and characterization of a novel type of membrane-associated prostaglandin E synthase". Biochem. Biophys. Res. Commun. 291 (4): 884–9. doi:10.1006/bbrc.2002.6531. PMID 11866447.
  4. ↑ Watanabe K, Ohkubo H, Niwa H, Tanikawa N, Koda N, Ito S, Ohmiya Y (2003). "Essential 110Cys in active site of membrane-associated prostaglandin E synthase-2". Biochem. Biophys. Res. Commun. 306 (2): 577–81. doi:10.1016/s0006-291x(03)01025-8. PMID 12804604.
  5. ↑ The gene encoding the PTGES2 protein contains 10 exons. The PTGE2 protein is a membrane-associated prostaglandin E synthase. Prostaglandin E synthase catalyzes the conversion of prostaglandin H2 to prostaglandin E2. The particular reaction catalyzed by PTGE2 is thought to be:
  6. ↑ "Salmonella infection data for Ptges2". Wellcome Trust Sanger Institute.
  7. ↑ "Citrobacter infection data for Ptges2". Wellcome Trust Sanger Institute.
  8. 1 2 3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
  9. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  10. ↑ "International Knockout Mouse Consortium".
  11. ↑ "Mouse Genome Informatics".
  12. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  13. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  14. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  15. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  16. 1 2 Rullah K, Mohd Aluwi MF, Yamin BM, Abdul Bahari MN, Wei LS, Ahmad S, Abas F, Ismail NH, Jantan I, Wai LK (Aug 2014). "Inhibition of prostaglandin E(2) production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation". Bioorganic & Medicinal Chemistry Letters 24 (16): 3826–34. doi:10.1016/j.bmcl.2014.06.061. PMID 25027933.
  17. ↑ Jongthawin J, Chusorn P, Techasen A, Loilome W, Boonmars T, Thanan R, Puapairoj A, Khuntikeo N, Tassaneeyakul W, Yongvanit P, Namwat N (Aug 2014). "PGE2 signaling and its biosynthesis-related enzymes in cholangiocarcinoma progression". Tumour Biology 35 (8): 8051–64. doi:10.1007/s13277-014-2021-y. PMID 24839005.
  18. ↑ Nitz I, Fisher E, Grallert H, Li Y, Gieger C, Rubin D, Boeing H, Spranger J, Lindner I, Schreiber S, Rathmann W, Gohlke H, Döring A, Wichmann HE, Schrezenmeir J, Döring F, Illig T (2007). "Association of prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism with type 2 diabetes in two German study populations". J. Clin. Endocrinol. Metab. 92 (8): 3183–8. doi:10.1210/jc.2006-2550. PMID 17566096.
  19. ↑ Lindner I, Helwig U, Rubin D, Fischer A, Marten B, Schreiber S, Döring F, Schrezenmeir J (2007). "Prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism and parameters of the metabolic syndrome". Mol Nutr Food Res 51 (12): 1447–51. doi:10.1002/mnfr.200700144. PMID 17979097.
  20. ↑ Wilhelms DB, Kirilov M, Mirrasekhian E, Eskilsson A, Kugelberg UÖ, Klar C, Ridder DA, Herschman HR, Schwaninger M, Blomqvist A, Engblom D (Aug 2014). "Deletion of prostaglandin E2 synthesizing enzymes in brain endothelial cells attenuates inflammatory fever". The Journal of Neuroscience 34 (35): 11684–90. doi:10.1523/JNEUROSCI.1838-14.2014. PMID 25164664.
  21. ↑ Ruan D, So SP (Oct 2014). "Prostaglandin E2 produced by inducible COX-2 and mPGES-1 promoting cancer cell proliferation in vitro and in vivo". Life Sciences 116 (1): 43–50. doi:10.1016/j.lfs.2014.07.042. PMID 25139833.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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