Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMLKWQ2)

• DOT Name: General transcription factor 3C polypeptide 6 (GTF3C6)
• Synonyms: Transcription factor IIIC 35 kDa subunit; TFIIIC 35 kDa subunit; TFIIIC35; Transcription factor IIIC subunit 6
• Gene Name: GTF3C6
• UniProt ID: TF3C6_HUMAN
• PDB ID: 8CLK
• Pfam ID: PF10419
• Sequence:
  MAAAADERSPEDGEDEEEEEQLVLVELSGIIDSDFLSKCENKCKVLGIDTERPILQVDSC
  VFAGEYEDTLGTCVIFEENVEHADTEGNNKTVLKYKCHTMKKLSMTRTLLTEKKEGEENI
  GGVEWLQIKDNDFSYRPNMICNFLHENEDEEVVASAPDKSLELEEEEIQMNDSSNLSCEQ
  EKPMHLEIEDSGPLIDIPSETEGSVFMETQMLP
• Function: Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters.
• Reactome Pathway:
  RNA Polymerase III Transcription Initiation From Type 1 Promoter (R-HSA-76061)
  RNA Polymerase III Transcription Initiation From Type 2 Promoter (R-HSA-76066)
  RNA Polymerase III Abortive And Retractive Initiation (R-HSA-749476)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of General transcription factor 3C polypeptide 6 (GTF3C6).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of General transcription factor 3C polypeptide 6 (GTF3C6).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of General transcription factor 3C polypeptide 6 (GTF3C6).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of General transcription factor 3C polypeptide 6 (GTF3C6).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of General transcription factor 3C polypeptide 6 (GTF3C6).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of General transcription factor 3C polypeptide 6 (GTF3C6).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of General transcription factor 3C polypeptide 6 (GTF3C6).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of General transcription factor 3C polypeptide 6 (GTF3C6).	[10]

2 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 affects the methylation of General transcription factor 3C polypeptide 6 (GTF3C6).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of General transcription factor 3C polypeptide 6 (GTF3C6).	[9]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] 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.
• [3] 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.
• [4] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.