Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWW4PN0)

• DOT Name: Transcription initiation factor IIA subunit 1 (GTF2A1)
• Synonyms: General transcription factor IIA subunit 1; TFIIAL; Transcription initiation factor TFIIA 42 kDa subunit; TFIIA-42
• Gene Name: GTF2A1
• Related Disease:
  Bipolar disorder
  Coeliac disease
  Gastric cancer
  Stomach cancer
• UniProt ID: TF2AA_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 ; 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: PF03153
• Sequence:
  MANSANTNTVPKLYRSVIEDVINDVRDIFLDDGVDEQVLMELKTLWENKLMQSRAVDGFH
  SEEQQLLLQVQQQHQPQQQQHHHHHHHQQAQPQQTVPQQAQTQQVLIPASQQATAPQVIV
  PDSKLIQHMNASNMSAAATAATLALPAGVTPVQQILTNSGQLLQVVRAANGAQYIFQPQQ
  SVVLQQQVIPQMQPGGVQAPVIQQVLAPLPGGISPQTGVIIQPQQILFTGNKTQVIPTTV
  AAPTPAQAQITATGQQQPQAQPAQTQAPLVLQVDGTGDTSSEEDEDEEEDYDDDEEEDKE
  KDGAEDGQVEEEPLNSEDDVSDEEGQELFDTENVVVCQYDKIHRSKNKWKFHLKDGIMNL
  NGRDYIFSKAIGDAEW
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[1]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[2]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[3]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[3]

4 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 1 (GTF2A1).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transcription initiation factor IIA subunit 1 (GTF2A1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the sumoylation of Transcription initiation factor IIA subunit 1 (GTF2A1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Transcription initiation factor IIA subunit 1 (GTF2A1).	[14]

10 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 1 (GTF2A1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription initiation factor IIA subunit 1 (GTF2A1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription initiation factor IIA subunit 1 (GTF2A1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transcription initiation factor IIA subunit 1 (GTF2A1).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transcription initiation factor IIA subunit 1 (GTF2A1).	[11]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Transcription initiation factor IIA subunit 1 (GTF2A1).	[12]
Gemcitabine	DMSE3I7	Approved	Gemcitabine affects the expression of Transcription initiation factor IIA subunit 1 (GTF2A1).	[13]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Transcription initiation factor IIA subunit 1 (GTF2A1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transcription initiation factor IIA subunit 1 (GTF2A1).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transcription initiation factor IIA subunit 1 (GTF2A1).	[17]

References

• [1] Integrated transcriptome and methylome analysis in youth at high risk for bipolar disorder: a preliminary analysis.Transl Psychiatry. 2017 Mar 14;7(3):e1059. doi: 10.1038/tp.2017.32.
• [2] Human genome search in celiac disease: mutated gliadin T-cell-like epitope in two human proteins promotes T-cell activation.J Mol Biol. 2002 Jun 7;319(3):593-602. doi: 10.1016/S0022-2836(02)00366-2.
• [3] Interaction of polymorphisms in the interleukin 1B-31 and general transcription factor 2A1 genes on the susceptibility to gastric cancer.Cytokine. 2007 May;38(2):96-100. doi: 10.1016/j.cyto.2007.05.008. Epub 2007 Jun 26.
• [4] 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.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Arsenic-induced sumoylation of Mus81 is involved in regulating genomic stability. Cell Cycle. 2017 Apr 18;16(8):802-811. doi: 10.1080/15384101.2017.1302628. Epub 2017 Mar 20.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [13] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [14] 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.
• [15] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.