Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTORBI4I)

• DOT Name: Transcription initiation factor TFIID subunit 9B (TAF9B)
• Synonyms: Neuronal cell death-related protein 7; DN-7; Transcription initiation factor TFIID subunit 9-like; Transcription-associated factor TAFII31L
• Gene Name: TAF9B
• UniProt ID: TAF9B_HUMAN
• PDB ID: 7KTR; 7KTS
• Pfam ID: PF02291
• Sequence:
  MESGKMAPPKNAPRDALVMAQILKDMGITEYEPRVINQMLEFAFRYVTTILDDAKIYSSH
  AKKPNVDADDVRLAIQCRADQSFTSPPPRDFLLDIARQKNQTPLPLIKPYAGPRLPPDRY
  CLTAPNYRLKSLIKKGPNQGRLVPRLSVGAVSSKPTTPTIATPQTVSVPNKVATPMSVTS
  QRFTVQIPPSQSTPVKPVPATTAVQNVLINPSMIGPKNILITTNMVSSQNTANEANPLKR
  KHEDDDDNDIM
• Function: Essential for cell viability. TAF9 and TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. May have a role in gene regulation associated with apoptosis. TAFs are components of the transcription factor IID (TFIID) complex, the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TFIID or TFTC are essential for the regulation of RNA polymerase II-mediated transcription.
• KEGG Pathway: Basal transcription factors (hsa03022)
• Reactome Pathway:
  RNA Polymerase II HIV Promoter Escape (R-HSA-167162)
  Transcription of the HIV genome (R-HSA-167172)
  Ub-specific processing proteases (R-HSA-5689880)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  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)
  HIV Transcription Initiation (R-HSA-167161)

Molecular Interaction Atlas (MIA) of This DOT

4 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 Transcription initiation factor TFIID subunit 9B (TAF9B).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription initiation factor TFIID subunit 9B (TAF9B).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Transcription initiation factor TFIID subunit 9B (TAF9B).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Transcription initiation factor TFIID subunit 9B (TAF9B).	[13]

15 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 Transcription initiation factor TFIID subunit 9B (TAF9B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat affects the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[9]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[16]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Transcription initiation factor TFIID subunit 9B (TAF9B).	[17]

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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] 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.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] 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.
• [7] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [8] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] 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.
• [14] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Chromatin modifiers: A new class of pollutants with potential epigenetic effects revealed by in vitro assays and transcriptomic analyses. Toxicology. 2023 Jan 15;484:153413. doi: 10.1016/j.tox.2022.153413. Epub 2022 Dec 26.