Details of Drug Off-Target (DOT)

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

• DOT Name: General transcription factor 3C polypeptide 2 (GTF3C2)
• Synonyms: TF3C-beta; Transcription factor IIIC 110 kDa subunit; TFIIIC 110 kDa subunit; TFIIIC110; Transcription factor IIIC subunit beta
• Gene Name: GTF3C2
• Related Disease:
  Gout
  Neoplasm
• UniProt ID: TF3C2_HUMAN
• PDB ID: 8CLI; 8CLJ; 8CLL
• Pfam ID: PF00400
• Sequence:
  MDTCGVGYVALGEAGPVGNMTVVDSPGQEVLNQLDVKTSSEMTSAEASVEMSLPTPLPGF
  EDSPDQRRLPPEQESLSRLEQPDLSSEMSKVSKPRASKPGRKRGGRTRKGPKRPQQPNPP
  SAPLVPGLLDQSNPLSTPMPKKRGRKSKAELLLLKLSKDLDRPESQSPKRPPEDFETPSG
  ERPRRRAAQVALLYLQELAEELSTALPAPVSCPEGPKVSSPTKPKKIRQPAACPGGEEVD
  GAPRDEDFFLQVEAEDVEESEGPSESSSEPEPVVPRSTPRGSTSGKQKPHCRGMAPNGLP
  NHIMAPVWKCLHLTKDFREQKHSYWEFAEWIPLAWKWHLLSELEAAPYLPQEEKSPLFSV
  QREGLPEDGTLYRINRFSSITAHPERWDVSFFTGGPLWALDWCPVPEGAGASQYVALFSS
  PDMNETHPLSQLHSGPGLLQLWGLGTLQQESCPGNRAHFVYGIACDNGCIWDLKFCPSGA
  WELPGTPRKAPLLPRLGLLALACSDGKVLLFSLPHPEALLAQQPPDAVKPAIYKVQCVAT
  LQVGSMQATDPSECGQCLSLAWMPTRPHQHLAAGYYNGMVVFWNLPTNSPLQRIRLSDGS
  LKLYPFQCFLAHDQAVRTLQWCKANSHFLVSAGSDRKIKFWDLRRPYEPINSIKRFLSTE
  LAWLLPYNGVTVAQDNCYASYGLCGIHYIDAGYLGFKAYFTAPRKGTVWSLSGSDWLGTI
  AAGDISGELIAAILPDMALNPINVKRPVERRFPIYKADLIPYQDSPEGPDHSSASSGVPN
  PPKARTYTETVNHHYLLFQDTDLGSFHDLLRREPMLRMQEGEGHSQLCLDRLQLEAIHKV
  RFSPNLDSYGWLVSGGQSGLVRIHFVRGLASPLGHRMQLESRAHFNAMFQPSSPTRRPGF
  SPTSHRLLPTP
• Function: Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. May play a direct role in stabilizing interactions of TFIIIC2 with TFIIIC1.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gout	DISHC0U7	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of General transcription factor 3C polypeptide 2 (GTF3C2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of General transcription factor 3C polypeptide 2 (GTF3C2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of General transcription factor 3C polypeptide 2 (GTF3C2).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of General transcription factor 3C polypeptide 2 (GTF3C2).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of General transcription factor 3C polypeptide 2 (GTF3C2).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of General transcription factor 3C polypeptide 2 (GTF3C2).	[8]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of General transcription factor 3C polypeptide 2 (GTF3C2).	[9]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of General transcription factor 3C polypeptide 2 (GTF3C2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of General transcription factor 3C polypeptide 2 (GTF3C2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of General transcription factor 3C polypeptide 2 (GTF3C2).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of General transcription factor 3C polypeptide 2 (GTF3C2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of General transcription factor 3C polypeptide 2 (GTF3C2).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of General transcription factor 3C polypeptide 2 (GTF3C2).	[11]

References

• [1] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [2] Clinical, histopathologic, and genomic features of Spitz tumors with ALK fusions.Am J Surg Pathol. 2015 May;39(5):581-91. doi: 10.1097/PAS.0000000000000387.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [7] 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.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [10] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [11] 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.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.