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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) Band 9q34.11 Start 128,120,693 bp End 128,128,462 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2|2 B Start 32,285,908 bp End 32,295,784 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart gastrocnemius muscle mucosa of transverse colon left ventricle right auricle 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
Wikidata
View/Edit Human View/Edit Mouse

Microsomal prostaglandin E synthase-2 (mPGES-2) or Prostaglandin E synthase 2 is an enzyme that in humans encoded by the PTGES2 gene located on chromosome 9. 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.

Structure

Microsomal prostaglandin E synthase type-2 (mPTGES2) has been crystallized with an anti-inflammatory drug indomethacin (IMN). 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.

Function

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

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.

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

Clinical significance

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

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

References

1. ^ GRCh38: Ensembl release 89: ENSG00000148334 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000026820 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Jakobsson PJ, Thorén S, Morgenstern R, et al. (1989). "Identification of human prostaglandin E synthase: a microsomal glutathione-dependent, inducible enzyme, constituting a potential novel drug target". Proc Natl Acad Sci USA. 96 (13): 7220–7225. Bibcode:1999PNAS...96.7220J. doi:10.1073/pnas.96.13.7220. PMC 22058. PMID 10377395.
6. Hui-Hua Chang, Emmanuelle J Meuillet (2011). "Identification and development of mPGES-1 inhibitors: where we are at?". Future Med Chem. 3 (15): 1909–1934. doi:10.4155/fmc.11.136. PMC 3232027. PMID 22023034.
7. 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.
8. ^ "Entrez Gene: prostaglandin E synthase 2".
9. "PTGES2 prostaglandin E synthase 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-18.
10. ^ Yamada T, Komoto J, Watanabe K, Ohmiya Y, Takusagawa F (May 2005). "Crystal structure and possible catalytic mechanism of microsomal prostaglandin E synthase type 2 (mPGES-2)". Journal of Molecular Biology. 348 (5): 1163–76. doi:10.1016/j.jmb.2005.03.035. PMID 15854652.
11. 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.
12. 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.
13. 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:
14. ^ 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" (PDF). Bioorganic & Medicinal Chemistry Letters. 24 (16): 3826–34. doi:10.1016/j.bmcl.2014.06.061. PMID 25027933.
15. 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. S2CID 10579551.
16. 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.
17. 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.
18. 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. PMC 6608410. PMID 25164664.
19. 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.

External links

• Overview of all the structural information available in the PDB for UniProt: Q9N0A4 (Macaca fascicularis (Crab-eating macaque)Prostaglandin E synthase 2) at the PDBe-KB.

Further reading

• Lehner B, Sanderson CM (Jul 2004). "A protein interaction framework for human mRNA degradation". Genome Research. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747.
• Palmieri RT, Wilson MA, Iversen ES, Clyde MA, Calingaert B, Moorman PG, Poole C, Anderson AR, Anderson S, Anton-Culver H, Beesley J, Hogdall E, Brewster W, Carney ME, Chen X, Chenevix-Trench G, Chang-Claude J, Cunningham JM, Dicioccio RA, Doherty JA, Easton DF, Edlund CK, Gayther SA, Gentry-Maharaj A, Goode EL, Goodman MT, Kjaer SK, Hogdall CK, Hopkins MP, Jenison EL, Blaakaer J, Lurie G, McGuire V, Menon U, Moysich KB, Ness RB, Pearce CL, Pharoah PD, Pike MC, Ramus SJ, Rossing MA, Song H, Terada KY, Vandenberg D, Vierkant RA, Wang-Gohrke S, Webb PM, Whittemore AS, Wu AH, Ziogas A, Berchuck A, Schildkraut JM (Dec 2008). "Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women". Cancer Epidemiology, Biomarkers & Prevention. 17 (12): 3567–72. doi:10.1158/1055-9965.EPI-08-0548. PMC 2664299. PMID 19064572.
• Chaudhry UA, Dore S (2009). "Cytosolic prostaglandin E synthase: expression patterns in control and Alzheimer's disease brains". American Journal of Alzheimer's Disease & Other Dementias. 24 (1): 46–51. doi:10.1177/1533317508323655. PMC 2859688. PMID 19001348.
• Wu T, Wu H, Wang J, Wang J (2011). "Expression and cellular localization of cyclooxygenases and prostaglandin E synthases in the hemorrhagic brain". Journal of Neuroinflammation. 8: 22. doi:10.1186/1742-2094-8-22. PMC 3062590. PMID 21385433.
• Dagle JM, Lepp NT, Cooper ME, Schaa KL, Kelsey KJ, Orr KL, Caprau D, Zimmerman CR, Steffen KM, Johnson KJ, Marazita ML, Murray JC (Apr 2009). "Determination of genetic predisposition to patent ductus arteriosus in preterm infants". Pediatrics. 123 (4): 1116–23. doi:10.1542/peds.2008-0313. PMC 2734952. PMID 19336370.
• Fischer A, Grallert H, Böhme M, Gieger C, Boomgaarden I, Heid I, Wichmann HE, Döring F, Illig T (Apr 2009). "Association analysis between the prostaglandin E synthase 2 R298H polymorphism and body mass index in 8079 participants of the KORA study cohort". Genetic Testing and Molecular Biomarkers. 13 (2): 223–6. doi:10.1089/gtmb.2008.0111. PMID 19371221.
• Mattila S, Tuominen H, Koivukangas J, Stenbäck F (Apr 2009). "The terminal prostaglandin synthases mPGES-1, mPGES-2, and cPGES are all overexpressed in human gliomas". Neuropathology. 29 (2): 156–65. doi:10.1111/j.1440-1789.2008.00963.x. PMID 19347995. S2CID 22681905.
• Lindner I, Helwig U, Rubin D, Fischer A, Marten B, Schreiber S, Döring F, Schrezenmeir J (Dec 2007). "Prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism and parameters of the metabolic syndrome". Molecular Nutrition & Food Research. 51 (12): 1447–51. doi:10.1002/mnfr.200700144. PMID 17979097.
• Seo T, Tatsuguchi A, Shinji S, Yonezawa M, Mitsui K, Tanaka S, Fujimori S, Gudis K, Fukuda Y, Sakamoto C (Jun 2009). "Microsomal prostaglandin E synthase protein levels correlate with prognosis in colorectal cancer patients". Virchows Archiv. 454 (6): 667–76. doi:10.1007/s00428-009-0777-z. PMID 19412621. S2CID 6233883.
• Lee E, Choi MK, Lee YJ, Ku JL, Kim KH, Choi JS, Lim SJ (Nov 2006). "Alpha-tocopheryl succinate, in contrast to alpha-tocopherol and alpha-tocopheryl acetate, inhibits prostaglandin E2 production in human lung epithelial cells". Carcinogenesis. 27 (11): 2308–15. doi:10.1093/carcin/bgl073. PMID 16714329.
• Meng Q, Raha A, Roy S, Hu J, Kalvakolanu DV (May 2005). "IFN-gamma-stimulated transcriptional activation by IFN-gamma-activated transcriptional element-binding factor 1 occurs via an inducible interaction with CAAAT/enhancer-binding protein-beta". Journal of Immunology. 174 (10): 6203–11. doi:10.4049/jimmunol.174.10.6203. PMID 15879117.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (Jan 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
• Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS (Dec 2005). "Transcriptome analysis of human gastric cancer". Mammalian Genome. 16 (12): 942–54. doi:10.1007/s00335-005-0075-2. PMID 16341674. S2CID 69278.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Chaudhry UA, Zhuang H, Crain BJ, Doré S (Jan 2008). "Elevated microsomal prostaglandin-E synthase-1 in Alzheimer's disease". Alzheimer's & Dementia. 4 (1): 6–13. doi:10.1016/j.jalz.2007.10.015. PMC 2500207. PMID 18631945.
• 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 (Aug 2007). "Association of prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism with type 2 diabetes in two German study populations". The Journal of Clinical Endocrinology and Metabolism. 92 (8): 3183–8. doi:10.1210/jc.2006-2550. PMID 17566096.
• Colombe L, Vindrios A, Michelet JF, Bernard BA (Sep 2007). "Prostaglandin metabolism in human hair follicle". Experimental Dermatology. 16 (9): 762–9. doi:10.1111/j.1600-0625.2007.00586.x. PMID 17697149. S2CID 43663330.
• Fisher E, Nitz I, Lindner I, Rubin D, Boeing H, Möhlig M, Hampe J, Schreiber S, Schrezenmeir J, Döring F (Feb 2007). "Candidate gene association study of type 2 diabetes in a nested case-control study of the EPIC-Potsdam cohort - role of fat assimilation". Molecular Nutrition & Food Research. 51 (2): 185–91. doi:10.1002/mnfr.200600162. PMID 17266179.

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

• Genes on human chromosome 9
• Genes mutated in mice