Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0190)
DME Name S-adenosylmethionine synthase 2 (MAT2A), Homo sapiens DME Info
UniProt ID
METK2_HUMAN
EC Number    EC: 2.5.1.6     (Click to Show/Hide the Complete EC Tree)
Transferase
Alkyl/aryl transferase
Alkyl/aryl transferase
EC: 2.5.1.6
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Interactome
Interactions between Xenobiotics and DME (XEOTIC)
      Fungicide(s), Herbicide(s) or Insecticide(s)
                  Pesticide/Insecticide Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Dicrotophos Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01050   XEOTIC Info Gene Form mRNA
                                 Classification Pesticide/Insecticide
                                 DME Modulation Dicrotophos up-regulates the expression of DME MAT2A [1]
      Health or Environmental Toxicant(s)
                  Acute Toxic Substance Click to Show/Hide the Full List of Xenobiotics:        5 Xenobiotics
                              2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01119   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine inhibits the expression of DME MAT2A [2]
                              2-butenal Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01122   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation 2-butenal inhibits the expression of DME MAT2A [3]
                              Chloropicrin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01247   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Chloropicrin inhibits the expression of DME MAT2A [4]
                              Formaldehyde Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01305   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Formaldehyde inhibits the expression of DME MAT2A [5], [6]
                              Nickel chloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01397   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Nickel chloride inhibits the expression of DME MAT2A [7]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene up-regulates the expression of DME MAT2A [8], [9]
                              Ethyl methanesulfonate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00772   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Ethyl methanesulfonate inhibits the expression of DME MAT2A [6]
                              Aflatoxin B1 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00806   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen-mycotoxin
                                 DME Modulation Aflatoxin B1 up-regulates the expression of DME MAT2A [10]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Acetaldehyde Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00872   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Acetaldehyde inhibits the expression of DME MAT2A [11]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Quercitrin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01449   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Quercitrin induces the drug-metabolizing activity of DME MAT2A [12]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      11 Xenobiotics
                              Cisplatin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00334   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cisplatin inhibits the expression of DME MAT2A [13]
                              Copper sulfate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00117   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Copper sulfate up-regulates the expression of DME MAT2A [14]
                              Cyclosporine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00241   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cyclosporine inhibits the expression of DME MAT2A [15]
                              Dexamethasone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00088   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Dexamethasone up-regulates the expression of DME MAT2A [16]
                              Doxorubicin hydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00292   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Doxorubicin hydrochloride inhibits the expression of DME MAT2A [17]
                              Estradiol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00090   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Estradiol up-regulates the expression of DME MAT2A [18], [19]
                              Fenofibrate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00035   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Fenofibrate inhibits the expression of DME MAT2A [20]
                              Folic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00404   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Folic acid up-regulates the expression of DME MAT2A [16]
                              Leflunomide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00053   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Leflunomide inhibits the expression of DME MAT2A [21]
                              Methotrexate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00366   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Methotrexate inhibits the expression of DME MAT2A [22]
                              Tretinoin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00253   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Tretinoin inhibits the drug-metabolizing activity of DME MAT2A [23]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              4-phenylbutyric acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00584   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2/3
                                 DME Modulation 4-phenylbutyric acid inhibits the expression of DME MAT2A [24]
                              Ethanol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00539   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Ethanol inhibits the expression of DME MAT2A [25]
                              MeIQx Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00609   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation MeIQx up-regulates the expression of DME MAT2A [2]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              (+)-JQ1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00723   XEOTIC Info Gene Form mRNA
                                 Classification Drug in Preclinical Study
                                 DME Modulation (+)-JQ1 inhibits the expression of DME MAT2A [26]
References
1 Molecular mechanisms of discrotophos-induced toxicity in HepG2 cells: The role of CSA in oxidative stress. Food Chem Toxicol. 2017 May;103:253-260.
2 Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.
3 Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.
4 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
5 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
6 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
7 Gene expression profiles in peripheral blood mononuclear cells of Chinese nickel refinery workers with high exposures to nickel and control subjects. Cancer Epidemiol Biomarkers Prev. 2013 Feb;22(2):261-9.
8 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
9 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
10 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
11 In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
12 Simultaneous action of the flavonoid quercetin on cytochrome P450 (CYP) 1A2, CYP2A6, N-acetyltransferase and xanthine oxidase activity in healthy volunteers. Clin Exp Pharmacol Physiol. 2009 Aug;36(8):828-33.
13 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
14 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
15 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
16 Low-dose methotrexate inhibits methionine S-adenosyltransferase in vitro and in vivo. Mol Med. 2012 May 9;18:423-32.
17 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
18 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
19 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
20 In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer. Mol Cancer. 2006 Mar 28;5:13.
21 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
22 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
23 Modulation of aromatase activity and mRNA by various selected pesticides in the human choriocarcinoma JEG-3 cell line. Toxicology. 2006 Nov 10;228(1):98-108.
24 Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
25 Ethanol inhibits methionine adenosyltransferase II activity and S-adenosylmethionine biosynthesis and enhances caspase-3-dependent cell death in T lymphocytes: relevance to alcohol-induced immunosuppression. J Nutr Biochem. 2008 Jun;19(6):384-91.
26 BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.

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