Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTGSI8P)

• DOT Name: General transcription factor 3C polypeptide 5 (GTF3C5)
• Synonyms: TF3C-epsilon; Transcription factor IIIC 63 kDa subunit; TFIIIC 63 kDa subunit; TFIIIC63; Transcription factor IIIC subunit epsilon
• Gene Name: GTF3C5
• UniProt ID: TF3C5_HUMAN
• PDB ID: 8CLK
• Pfam ID: PF09734 ; PF17682
• Sequence:
  MAAEAADLGLGAAVPVELRRERRMVCVEYPGVVRDVAKMLPTLGGEEGVSRIYADPTKRL
  ELYFRPKDPYCHPVCANRFSTSSLLLRIRKRTRRQKGVLGTEAHSEVTFDMEILGIISTI
  YKFQGMSDFQYLAVHTEAGGKHTSMYDKVLMLRPEKEAFFHQELPLYIPPPIFSRLDAPV
  DYFYRPETQHREGYNNPPISGENLIGLSRARRPHNAIFVNFEDEEVPKQPLEAAAQTWRR
  VCTNPVDRKVEEELRKLFDIRPIWSRNAVKANISVHPDKLKVLLPFIAYYMITGPWRSLW
  IRFGYDPRKNPDAKIYQVLDFRIRCGMKHGYAPSDLPVKAKRSTYNYSLPITVKKTSSQL
  VTMHDLKQGLGPSGTSGARKPASSKYKLKDSVYIFREGALPPYRQMFYQLCDLNVEELQK
  IIHRNDGAENSCTERDGWCLPKTSDELRDTMSLMIRQTIRSKRPALFSSSAKADGGKEQL
  TYESGEDEEDEEEEEEEEEDFKPSDGSENEMETEILDYV
• 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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of General transcription factor 3C polypeptide 5 (GTF3C5).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of General transcription factor 3C polypeptide 5 (GTF3C5).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of General transcription factor 3C polypeptide 5 (GTF3C5).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of General transcription factor 3C polypeptide 5 (GTF3C5).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of General transcription factor 3C polypeptide 5 (GTF3C5).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of General transcription factor 3C polypeptide 5 (GTF3C5).	[4]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of General transcription factor 3C polypeptide 5 (GTF3C5).	[7]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of General transcription factor 3C polypeptide 5 (GTF3C5).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] 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.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] 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.
• [6] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [7] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [8] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.