Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP0QOAL)

• DOT Name: Thiol S-methyltransferase TMT1B (TMT1B)
• Synonyms: EC 2.1.1.9; Methyltransferase-like protein 7B; Thiol S-methyltransferase METTL7B
• Gene Name: TMT1B
• UniProt ID: TMT1B_HUMAN
• EC Number: 2.1.1.9
• Pfam ID: PF08241
• Sequence:
  MDILVPLLQLLVLLLTLPLHLMALLGCWQPLCKSYFPYLMAVLTPKSNRKMESKKRELFS
  QIKGLTGASGKVALLELGCGTGANFQFYPPGCRVTCLDPNPHFEKFLTKSMAENRHLQYE
  RFVVAPGEDMRQLADGSMDVVVCTLVLCSVQSPRKVLQEVRRVLRPGGVLFFWEHVAEPY
  GSWAFMWQQVFEPTWKHIGDGCCLTRETWKDLENAQFSEIQMERQPPPLKWLPVGPHIMG
  KAVK
• Function: Thiol S-methyltransferase that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to alkyl and phenolic thiol-containing acceptor substrates. Together with TMT1B accounts for most of S-thiol methylation activity in the endoplasmic reticulum of hepatocytes. Selectively methylates S-centered nucleophiles from metabolites such as hydrogen sulfide and dithiothreitol.
• Tissue Specificity: Expressed in the liver.

Molecular Interaction Atlas (MIA) of This DOT

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[7]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[9]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Thiol S-methyltransferase TMT1B (TMT1B).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Thiol S-methyltransferase TMT1B (TMT1B).	[10]

References

• [1] 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.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] 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.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Differently expressed long noncoding RNAs and mRNAs in TK6 cells exposed to low dose hydroquinone. Oncotarget. 2017 Oct 4;8(56):95554-95567. doi: 10.18632/oncotarget.21481. eCollection 2017 Nov 10.
• [9] 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.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.