Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVXS75P)

• DOT Name: General transcription factor IIF subunit 1 (GTF2F1)
• Synonyms: General transcription factor IIF 74 kDa subunit; Transcription initiation factor IIF subunit alpha; TFIIF-alpha; Transcription initiation factor RAP74
• Gene Name: GTF2F1
• Related Disease:
  Inflammatory bowel disease
  Epithelial ovarian cancer
• UniProt ID: T2FA_HUMAN
• PDB ID: 1F3U ; 1I27 ; 1J2X ; 1NHA ; 1ONV ; 2K7L ; 5IY6 ; 5IY7 ; 5IY8 ; 5IY9 ; 5IYA ; 5IYB ; 5IYC ; 5IYD ; 6O9L ; 7EDX ; 7EG7 ; 7EG8 ; 7EG9 ; 7EGA ; 7EGB ; 7EGC ; 7ENA ; 7ENC ; 7LBM ; 7NVR ; 7NVS ; 7NVT ; 7NVU ; 7NVY ; 7NVZ ; 7NW0 ; 7ZWD ; 7ZX7 ; 7ZX8 ; 8BVW ; 8BYQ ; 8BZ1 ; 8GXQ ; 8GXS ; 8WAK ; 8WAL ; 8WAN ; 8WAO ; 8WAP ; 8WAQ ; 8WAR ; 8WAS ; 8WAT ; 8WAU ; 8WAV ; 8WAW ; 8WAX ; 8WAY ; 8WAZ ; 8WB0
• Pfam ID: PF05793
• Sequence:
  MAALGPSSQNVTEYVVRVPKNTTKKYNIMAFNAADKVNFATWNQARLERDLSNKKIYQEE
  EMPESGAGSEFNRKLREEARRKKYGIVLKEFRPEDQPWLLRVNGKSGRKFKGIKKGGVTE
  NTSYYIFTQCPDGAFEAFPVHNWYNFTPLARHRTLTAEEAEEEWERRNKVLNHFSIMQQR
  RLKDQDQDEDEEEKEKRGRRKASELRIHDLEDDLEMSSDASDASGEEGGRVPKAKKKAPL
  AKGGRKKKKKKGSDDEAFEDSDDGDFEGQEVDYMSDGSSSSQEEPESKAKAPQQEEGPKG
  VDEQSDSSEESEEEKPPEEDKEEEEEKKAPTPQEKKRRKDSSEESDSSEESDIDSEASSA
  LFMAKKKTPPKRERKPSGGSSRGNSRPGTPSAEGGSTSSTLRAAASKLEQGKRVSEMPAA
  KRLRLDTGPQSLSGKSTPQPPSGKTTPNSGDVQVTEDAVRRYLTRKPMTTKDLLKKFQTK
  KTGLSSEQTVNVLAQILKRLNPERKMINDKMHFSLKE
• Function: TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It promotes transcription elongation.
• KEGG Pathway: Basal transcription factors (hsa03022)
• Reactome Pathway:
  Formation of the Early Elongation Complex (R-HSA-113418)
  Formation of HIV elongation complex in the absence of HIV Tat (R-HSA-167152)
  Formation of the HIV-1 Early Elongation Complex (R-HSA-167158)
  RNA Pol II CTD phosphorylation and interaction with CE during HIV infection (R-HSA-167160)
  HIV Transcription Initiation (R-HSA-167161)
  RNA Polymerase II HIV Promoter Escape (R-HSA-167162)
  Transcription of the HIV genome (R-HSA-167172)
  Formation of HIV-1 elongation complex containing HIV-1 Tat (R-HSA-167200)
  Pausing and recovery of Tat-mediated HIV elongation (R-HSA-167238)
  Abortive elongation of HIV-1 transcript in the absence of Tat (R-HSA-167242)
  Tat-mediated HIV elongation arrest and recovery (R-HSA-167243)
  Tat-mediated elongation of the HIV-1 transcript (R-HSA-167246)
  HIV elongation arrest and recovery (R-HSA-167287)
  Pausing and recovery of HIV elongation (R-HSA-167290)
  Viral Messenger RNA Synthesis (R-HSA-168325)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  FGFR2 alternative splicing (R-HSA-6803529)
  RNA polymerase II transcribes snRNA genes (R-HSA-6807505)
  mRNA Capping (R-HSA-72086)
  mRNA Splicing - Major Pathway (R-HSA-72163)
  mRNA Splicing - Minor Pathway (R-HSA-72165)
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  RNA Polymerase II Promoter Escape (R-HSA-73776)
  RNA Polymerase II Transcription Pre-Initiation And Promoter Opening (R-HSA-73779)
  RNA Polymerase II Transcription Initiation (R-HSA-75953)
  RNA Polymerase II Transcription Elongation (R-HSA-75955)
  RNA Polymerase II Transcription Initiation And Promoter Clearance (R-HSA-76042)
  RNA Pol II CTD phosphorylation and interaction with CE (R-HSA-77075)
  Signaling by FGFR2 IIIa TM (R-HSA-8851708)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Formation of RNA Pol II elongation complex (R-HSA-112382)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[2]

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 IIF subunit 1 (GTF2F1).	[3]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of General transcription factor IIF subunit 1 (GTF2F1).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of General transcription factor IIF subunit 1 (GTF2F1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of General transcription factor IIF subunit 1 (GTF2F1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of General transcription factor IIF subunit 1 (GTF2F1).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of General transcription factor IIF subunit 1 (GTF2F1).	[6]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of General transcription factor IIF subunit 1 (GTF2F1).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of General transcription factor IIF subunit 1 (GTF2F1).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of General transcription factor IIF subunit 1 (GTF2F1).	[6]

References

• [1] Genome-wide analysis identifies rare copy number variations associated with inflammatory bowel disease.PLoS One. 2019 Jun 11;14(6):e0217846. doi: 10.1371/journal.pone.0217846. eCollection 2019.
• [2] BTF4/BTNA3.2 and GCS as candidate mRNA prognostic markers in epithelial ovarian cancer.Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):913-20. doi: 10.1158/1055-9965.EPI-07-0692.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [8] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] 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.