Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE5Q4OS)

• DOT Name: Transcription initiation factor IIA subunit 2 (GTF2A2)
• Synonyms: General transcription factor IIA subunit 2; TFIIA p12 subunit; TFIIA-12; TFIIAS; Transcription initiation factor IIA gamma chain; TFIIA-gamma
• Gene Name: GTF2A2
• UniProt ID: T2AG_HUMAN
• PDB ID: 1NVP ; 5FUR ; 5IY6 ; 5IY7 ; 5IY8 ; 5IY9 ; 5IYA ; 5IYB ; 5IYC ; 5IYD ; 5M4S ; 6MZM ; 6O9L ; 7EDX ; 7EG7 ; 7EG8 ; 7EG9 ; 7EGA ; 7EGB ; 7EGC ; 7EGD ; 7EGI ; 7EGJ ; 7ENA ; 7ENC ; 7LBM ; 7NVR ; 7NVS ; 7NVT ; 7NVU ; 7NVY ; 7NVZ ; 7NW0 ; 7ZWC ; 7ZWD ; 7ZX7 ; 7ZX8 ; 7ZXE ; 8BVW ; 8BYQ ; 8BZ1 ; 8GXQ ; 8GXS ; 8WAK ; 8WAL ; 8WAN ; 8WAO ; 8WAP ; 8WAQ ; 8WAR ; 8WAS
• Pfam ID: PF02751 ; PF02268
• Sequence:
  MAYQLYRNTTLGNSLQESLDELIQSQQITPQLALQVLLQFDKAINAALAQRVRNRVNFRG
  SLNTYRFCDNVWTFVLNDVEFREVTELIKVDKVKIVACDGKNTGSNTTE
• Function: TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation. TFIIA in a complex with TBP mediates transcriptional activity.
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  RNA Polymerase II HIV Promoter Escape (R-HSA-167162)
  Transcription of the HIV genome (R-HSA-167172)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  RNA polymerase II transcribes snRNA genes (R-HSA-6807505)
  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 Initiation And Promoter Clearance (R-HSA-76042)
  Estrogen-dependent gene expression (R-HSA-9018519)
  HIV Transcription Initiation (R-HSA-167161)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Transcription initiation factor IIA subunit 2 (GTF2A2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription initiation factor IIA subunit 2 (GTF2A2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription initiation factor IIA subunit 2 (GTF2A2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transcription initiation factor IIA subunit 2 (GTF2A2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transcription initiation factor IIA subunit 2 (GTF2A2).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription initiation factor IIA subunit 2 (GTF2A2).	[5]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Transcription initiation factor IIA subunit 2 (GTF2A2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription initiation factor IIA subunit 2 (GTF2A2).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transcription initiation factor IIA subunit 2 (GTF2A2).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transcription initiation factor IIA subunit 2 (GTF2A2).	[10]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Transcription initiation factor IIA subunit 2 (GTF2A2).	[11]

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] Transcription Factor IIA tau is associated with undifferentiated cells and its gene expression is repressed in primary neurons at the chromatin level in vivo. Stem Cells Dev. 2006 Apr;15(2):175-90. doi: 10.1089/scd.2006.15.175.
• [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] 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] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [7] 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.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.