MPGES-1

PTGES
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3DWW, 4WAB, 4AL1, 4BPM, 4YL1, 4YL3, 4YK5, 4AL0, 4YL0, 5BQI, 5BQG, 5BQH
Identifiers
Aliases	PTGES , MGST-IV, MGST1-L1, MGST1L1, MPGES, PGES, PIG12, PP102, PP1294, TP53I12, mPGES-1, prostaglandin E synthase
External IDs	OMIM: 605172; MGI: 1927593; HomoloGene: 3587; GeneCards: PTGES; OMA:PTGES - orthologs
Gene location (Human) Chr. Chromosome 9 (human) [1] Band 9q34.11 Start 129,738,331 bp [1] End 129,753,042 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2 B|2 21.75 cM Start 30,779,483 bp [2] End 30,819,875 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in palpebral conjunctiva nasal epithelium gastric mucosa seminal vesicula cartilage tissue skin of leg mucosa of urinary bladder skin of abdomen nipple minor salivary glands Top expressed in blastocyst gastrula morula lactiferous gland decidua right kidney cumulus cell genital tubercle lumbar spinal ganglion granulocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function glutathione binding isomerase activity prostaglandin-E synthase activity glutathione transferase activity Cellular component cytoplasm integral component of membrane endoplasmic reticulum membrane intracellular membrane-bounded organelle membrane nuclear envelope lumen perinuclear region of cytoplasm mitochondrion Biological process prostaglandin metabolic process response to cytokine response to organic cyclic compound response to retinoic acid lipid metabolism cyclooxygenase pathway fatty acid metabolic process response to calcium ion response to lipopolysaccharide fatty acid biosynthetic process acute inflammatory response prostaglandin biosynthetic process chronic inflammatory response negative regulation of cell population proliferation signal transduction glutathione metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9536 64292 Ensembl ENSG00000148344 ENSMUSG00000050737 UniProt O14684 Q9JM51 RefSeq (mRNA) NM_004878 NM_198797 NM_022415 RefSeq (protein) NP_004869 NP_071860 Location (UCSC) Chr 9: 129.74 – 129.75 Mb Chr 2: 30.78 – 30.82 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Microsomal prostaglandin E synthase-1 (mPGES-1) ^{[5] [6]} or Prostaglandin E synthase is an enzyme that in humans is encoded by the PTGES gene. ^{[7] [8] [9]}

The protein encoded by this gene is a glutathione-dependent prostaglandin E synthase. The expression of this gene has been shown to be induced by proinflammatory cytokine interleukin 1 beta (IL1B). Its expression can also be induced by tumor suppressor protein TP53, and may be involved in TP53-induced apoptosis.

Knockout studies in mice suggest that this gene may contribute to the pathogenesis of collagen-induced arthritis and mediate acute pain during inflammatory responses. ^[9]

It is inhibited by crisdesalazine (AAD-2004; GedaCure). ^[10]

See also

• Prostaglandin E synthase

References

1. GRCh38: Ensembl release 89: ENSG00000148344 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000050737 – 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. Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B (Sep 1997). "A model for p53-induced apoptosis". Nature. 389 (6648): 300–5. Bibcode:1997Natur.389..300P. doi:10.1038/38525. PMID   9305847. S2CID   4429638.
8. Jakobsson PJ, Morgenstern R, Mancini J, Ford-Hutchinson A, Persson B (May 1999). "Common structural features of MAPEG -- a widespread superfamily of membrane-associated proteins with highly divergent functions in eicosanoid and glutathione metabolism". Protein Sci. 8 (3): 689–92. doi:10.1110/ps.8.3.689. PMC   2144274 . PMID   10091672.
9. "Entrez Gene: PTGES prostaglandin E synthase".
10. Dunkel P, Chai CL, Sperlágh B, Huleatt PB, Mátyus P (September 2012). "Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis". Expert Opin Investig Drugs. 21 (9): 1267–308. doi:10.1517/13543784.2012.703178. PMID   22741814.

Further reading

• Bastien L, Sawyer N, Grygorczyk R, et al. (1994). "Cloning, functional expression, and characterization of the human prostaglandin E2 receptor EP2 subtype". J. Biol. Chem. 269 (16): 11873–7. doi: 10.1016/S0021-9258(17)32654-6 . PMID   8163486.
• Wu T, Wu H, Wang J, Wang J (2011). "Expression and cellular localization of cyclooxygenases and prostaglandin E synthases in the hemorrhagic brain". J Neuroinflammation. 8: 22. doi: 10.1186/1742-2094-8-22 . PMC   3062590 . PMID   21385433.
• Funk CD, Furci L, FitzGerald GA, et al. (1994). "Cloning and expression of a cDNA for the human prostaglandin E receptor EP1 subtype". J. Biol. Chem. 268 (35): 26767–72. doi: 10.1016/S0021-9258(19)74379-8 . PMID   8253813.
• Giacomini E, Giordani L, di Modugno F, et al. (1998). "Increased PGE2 production mediates the in vitro inhibitory effect of the human immunodeficiency virus P24 immunosuppressive heptapeptide Ch7". Scand. J. Immunol. 48 (3): 248–53. doi:10.1046/j.1365-3083.1998.00389.x. PMID   9743208. S2CID   20332912.
• Jakobsson PJ, Thorén S, Morgenstern R, Samuelsson B (1999). "Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target". Proc. Natl. Acad. Sci. U.S.A. 96 (13): 7220–5. Bibcode:1999PNAS...96.7220J. doi: 10.1073/pnas.96.13.7220 . PMC   22058 . PMID   10377395.
• Forsberg L, Leeb L, Thorén S, et al. (2000). "Human glutathione dependent prostaglandin E synthase: gene structure and regulation". FEBS Lett. 471 (1): 78–82. doi:10.1016/S0014-5793(00)01367-3. PMID   10760517. S2CID   10901322.
• Han R, Smith TJ (2002). "Cytoplasmic prostaglandin E2 synthase is dominantly expressed in cultured KAT-50 thyrocytes, cells that express constitutive prostaglandin-endoperoxide H synthase-2. Basis for low protaglandin E2 production". J. Biol. Chem. 277 (39): 36897–903. doi: 10.1074/jbc.M206949200 . PMID   12145315.
• Giannoulias D, Alfaidy N, Holloway AC, et al. (2002). "Expression of prostaglandin I(2) synthase, but not prostaglandin E synthase, changes in myometrium of women at term pregnancy". J. Clin. Endocrinol. Metab. 87 (11): 5274–82. doi: 10.1210/jc.2002-020521 . PMID   12414902.
• Ouellet M, Falgueyret JP, Ear PH, et al. (2003). "Purification and characterization of recombinant microsomal prostaglandin E synthase-1". Protein Expr. Purif. 26 (3): 489–95. doi:10.1016/S1046-5928(02)00566-1. PMID   12460774.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Uracz W, Uracz D, Olszanecki R, Gryglewski RJ (2003). "Interleukin 1beta induces functional prostaglandin E synthase in cultured human umbilical vein endothelial cells". J. Physiol. Pharmacol. 53 (4 Pt 1): 643–54. PMID   12512699.
• Meadows JW, Eis AL, Brockman DE, Myatt L (2003). "Expression and localization of prostaglandin E synthase isoforms in human fetal membranes in term and preterm labor". J. Clin. Endocrinol. Metab. 88 (1): 433–9. doi: 10.1210/jc.2002-021061 . PMID   12519887.
• Kamei D, Murakami M, Nakatani Y, et al. (2003). "Potential role of microsomal prostaglandin E synthase-1 in tumorigenesis". J. Biol. Chem. 278 (21): 19396–405. doi: 10.1074/jbc.M213290200 . PMID   12626523.
• Jakobsson PJ, Thorén S, Morgenstern R, Samuelsson B (2003). "Characterization of Microsomal, Glutathione Dependent Prostaglandin e Synthase". Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5. Advances in Experimental Medicine and Biology. Vol. 507. pp. 287–91. doi:10.1007/978-1-4615-0193-0_44. ISBN   978-0-306-47283-1. PMID   12664599.
• Thorén S, Weinander R, Saha S, et al. (2003). "Human microsomal prostaglandin E synthase-1: purification, functional characterization, and projection structure determination". J. Biol. Chem. 278 (25): 22199–209. doi: 10.1074/jbc.M303227200 . PMID   12672824.
• Alfaidy N, Sun M, Challis JR, Gibb W (2003). "Expression of membrane prostaglandin E synthase in human placenta and fetal membranes and effect of labor". Endocrine. 20 (3): 219–25. doi:10.1385/ENDO:20:3:219. PMID   12721500. S2CID   9590845.
• Ekström L, Lyrenäs L, Jakobsson PJ, et al. (2003). "Basal expression of the human MAPEG members microsomal glutathione transferase 1 and prostaglandin E synthase genes is mediated by Sp1 and Sp3". Biochim. Biophys. Acta. 1627 (2–3): 79–84. doi:10.1016/S0167-4781(03)00077-0. PMID   12818425.
• Murakami M, Nakashima K, Kamei D, et al. (2003). "Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2". J. Biol. Chem. 278 (39): 37937–47. doi: 10.1074/jbc.M305108200 . PMID   12835322.
• Trebino CE, Stock JL, Gibbons CP, et al. (2003). "Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase". Proc. Natl. Acad. Sci. U.S.A. 100 (15): 9044–9. Bibcode:2003PNAS..100.9044T. doi: 10.1073/pnas.1332766100 . PMC   166435 . PMID   12835414.