Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0162)
DME Name Transglutaminase H (TGM2), Homo sapiens DME Info
UniProt ID
TGM2_HUMAN
EC Number    EC: 2.3.2.13     (Click to Show/Hide the Complete EC Tree)
Transferase
Acyltransferase
Aminoacyltransferase
EC: 2.3.2.13
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)
      Health or Environmental Toxicant(s)
                  Acute Toxic Substance Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              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 TGM2 [1]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene inhibits the expression of DME TGM2 [2]
                              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 TGM2 [3]
                  Environmental Pollutant Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Enzacamene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00903   XEOTIC Info Gene Form mRNA
                                 Classification Environmental Pollutant
                                 DME Modulation Enzacamene inhibits the expression of DME TGM2 [4]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01145   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation 4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid induces the drug-metabolizing activity of DME TGM2 [5]
                              Diethylhexyl phthalate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01004   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Diethylhexyl phthalate inhibits the drug-metabolizing activity of DME TGM2 [6]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Mixture Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Tobacco smoke pollution Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00821   XEOTIC Info Gene Form Protein
                                 Classification Natural Mixture
                                 DME Modulation Tobacco smoke pollution inhibits the drug-metabolizing activity of DME TGM2 [7]
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        4 Xenobiotics
                              4-oxoretinoic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01154   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation 4-oxoretinoic acid up-regulates the expression of DME TGM2 [8]
                              4-oxoretinol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01155   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation 4-oxoretinol up-regulates the expression of DME TGM2 [8]
                              Isoxazole Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00786   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Isoxazole inhibits the drug-metabolizing activity of DME TGM2 [9]
                              Quercitrin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01449   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation Quercitrin inhibits the expression of DME TGM2 [10]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      14 Xenobiotics
                              Acetaminophen Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00217   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Acetaminophen inhibits the expression of DME TGM2 [11]
                              Alitretinoin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00167   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Alitretinoin induces the drug-metabolizing activity of DME TGM2 [5]
                              Beta carotene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00401   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Beta carotene up-regulates the expression of DME TGM2 [8]
                              Bexarotene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00144   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Bexarotene up-regulates the expression of DME TGM2 [12]
                              Calcitriol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00184   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Calcitriol up-regulates the expression of DME TGM2 [13], [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 TGM2 [15]
                              Doxorubicin hydrochloride Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00292   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Doxorubicin hydrochloride up-regulates the expression of DME TGM2 [16], [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 TGM2 [18], [19]
                              Piroxicam Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00204   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Piroxicam inhibits the drug-metabolizing activity of DME TGM2 [20]
                              Progesterone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00094   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Progesterone up-regulates the expression of DME TGM2 [21]
                              Rosiglitazone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00380   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Rosiglitazone up-regulates the expression of DME TGM2 and leads to increasing the drug-metabolizing activity of this enzyme [22]
                              Testosterone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00095   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Testosterone up-regulates the expression of DME TGM2 [23]
                              Tretinoin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00253   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Tretinoin induces the drug-metabolizing activity of DME TGM2 [24]
                              Valproic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00029   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Valproic acid up-regulates the expression of DME TGM2 [25]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Triclosan Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00560   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Triclosan inhibits the drug-metabolizing activity of DME TGM2 [26]
                              Vitamin A Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00551   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Vitamin A up-regulates the expression of DME TGM2 [27]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Bisphenol A Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01226   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Bisphenol A inhibits the expression of DME TGM2 [28]
                              Ethanol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00539   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Ethanol induces the drug-metabolizing activity of DME TGM2 [29]
                              MS-275 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00581   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation MS-275 up-regulates the expression of DME TGM2 [30]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Hexylresorcinol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01329   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Hexylresorcinol inhibits the drug-metabolizing activity of DME TGM2 [31]
                              Quercetin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00538   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Quercetin inhibits the expression of DME TGM2 [32]
                              Trichostatin A Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01492   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Trichostatin A up-regulates the expression of DME TGM2 [33]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        2 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 TGM2 [34], [35]
                              AM-580 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00728   XEOTIC Info Gene Form Protein
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation AM-580 induces the drug-metabolizing activity of DME TGM2 [36]
References
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2 Gene expression profiling of A549 cells exposed to Milan PM2.5. Toxicol Lett. 2012 Mar 7;209(2):136-45.
3 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
4 4-Methylbenzylidene-camphor inhibits proliferation and induces reactive oxygen species-mediated apoptosis of human trophoblast cells. Reprod Toxicol. 2019 Mar;84:49-58.
5 Retinoic acid receptors and tissue-transglutaminase mediate short-term effect of retinoic acid on migration and invasion of neuroblastoma SH-SY5Y cells. Oncogene. 2006 Jan 12;25(2):240-7.
6 Di-(2-ethylhexyl)-phthalate induces apoptosis via the PPARgama/PTEN/AKT pathway in differentiated human embryonic stem cells. Food Chem Toxicol. 2019 Sep;131:110552.
7 Expression and kinetic properties of a recombinant 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzyme of human liver. J Biochem. 1995 Aug;118(2):285-90.
8 Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
9 Chemistry and biology of dihydroisoxazole derivatives: selective inhibitors of human transglutaminase 2. Chem Biol. 2005 Apr;12(4):469-75.
10 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
11 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
12 Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res. 2006 Dec 15;66(24):12009-18.
13 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
14 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
15 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
16 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.
17 Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype. Oncogene. 2005 Jul 14;24(30):4765-77.
18 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
19 Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
20 Synthesis, biological activity, and preliminary pharmacokinetic evaluation of analogues of a phosphosulfomannan angiogenesis inhibitor (PI-88). J Med Chem. 2005 Dec 29;48(26):8229-36.
21 Tissue-specific, inducible, and hormonal control of the human UDP-glucuronosyltransferase-1 (UGT1) locus. J Biol Chem. 2005 Nov 11;280(45):37547-57.
22 Regulation of cytochrome P450 2C9 expression in primary cultures of human hepatocytes. J Biochem Mol Toxicol. 2009 Jan-Feb;23(1):43-58.
23 The azole fungicide tebuconazole affects human CYP1A1 and CYP1A2 expression by an aryl hydrocarbon receptor-dependent pathway. Food Chem Toxicol. 2019 Jan;123:481-491.
24 The effect of Topotecan on oxidative stress in MCF-7 human breast cancer cell line. Acta Biochim Pol. 2005;52(4):897-902.
25 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
26 Trichlorfon induces apoptosis in SH-SY5Y neuroblastoma cells via the endoplasmic reticulum? Chem Biol Interact. 2009 Sep 14;181(1):37-44.
27 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
28 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
29 NF-kappaB-activated tissue transglutaminase is involved in ethanol-induced hepatic injury and the possible role of propolis in preventing fibrogenesis. Toxicology. 2008 Apr 18;246(2-3):148-57.
30 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
31 4-Hexylresorcinol inhibits transglutaminase-2 activity and has synergistic effects along with cisplatin in KB cells. Oncol Rep. 2011 Jun;25(6):1597-602.
32 Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis. Toxicol In Vitro. 2015 Oct;29(7):1669-82.
33 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
34 PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
35 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
36 New benzoic acid derivatives with retinoid activity: lack of direct correlation between biological activity and binding to cellular retinoic acid binding protein. Cancer Res. 1987 Jul 1;47(13):3523-7.

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