Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVMULE9)

• DOT Name: Transcription initiation factor TFIID subunit 3 (TAF3)
• Synonyms: 140 kDa TATA box-binding protein-associated factor; TBP-associated factor 3; Transcription initiation factor TFIID 140 kDa subunit; TAF(II)140; TAF140; TAFII-140; TAFII140
• Gene Name: TAF3
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
• UniProt ID: TAF3_HUMAN
• PDB ID: 5C13; 5WXG; 5WXH; 5XMY; 6MZD; 6MZL; 7EDX; 7EG7; 7EG8; 7EG9; 7EGA; 7EGB; 7EGC; 7EGD; 7EGE; 7EGF; 7EGI; 7EGJ; 7ENA; 7ENC; 8GXQ; 8GXS; 8WAK; 8WAL; 8WAN; 8WAO; 8WAP; 8WAQ; 8WAR; 8WAS
• Pfam ID: PF07524 ; PF00628
• Sequence:
  MCESYSRSLLRVSVAQICQALGWDSVQLSACHLLTDVLQRYLQQLGRGCHRYSELYGRTD
  PILDDVGEAFQLMGVSLHELEDYIHNIEPVTFPHQIPSFPVSKNNVLQFPQPGSKDAEER
  KEYIPDYLPPIVSSQEEEEEEQVPTDGGTSAEAMQVPLEEDDELEEEEIINDENFLGKRP
  LDSPEAEELPAMKRPRLLSTKGDTLDVVLLEAREPLSSINTQKIPPMLSPVHVQDSTDLA
  PPSPEPPMLAPVAKSQMPTAKPLETKSFTPKTKTKTSSPGQKTKSPKTAQSPAMVGSPIR
  SPKTVSKEKKSPGRSKSPKSPKSPKVTTHIPQTPVRPETPNRTPSATLSEKISKETIQVK
  QIQTPPDAGKLNSENQPKKAVVADKTIEASIDAVIARACAEREPDPFEFSSGSESEGDIF
  TSPKRISGPECTTPKASTSANNFTKSGSTPLPLSGGTSSSDNSWTMDASIDEVVRKAKLG
  TPSNMPPNFPYISSPSVSPPTPEPLHKVYEEKTKLPSSVEVKKKLKKELKTKMKKKEKQR
  DREREKDKNKDKSKEKDKVKEKEKDKETGRETKYPWKEFLKEEEADPYKFKIKEFEDVDP
  KVKLKDGLVRKEKEKHKDKKKDREKGKKDKDKREKEKVKDKGREDKMKAPAPPLVLPPKE
  LALPLFSPATASRVPAMLPSLLPVLPEKLFEEKEKVKEKEKKKDKKEKKKKKEKEKEKKE
  KEREKEKREREKREKEKEKHKHEKIKVEPVALAPSPVIPRLTLRVGAGQDKIVISKVVPA
  PEAKPAPSQNRPKTPPPAPAPAPGPMLVSPAPVPLPLLAQAAAGPALLPSPGPAASGASA
  KAPVRSVVTETVSTYVIRDEWGNQIWICPGCNKPDDGSPMIGCDDCDDWYHWPCVGIMTA
  PPEEMQWFCPKCANKKKDKKHKKRKHRAH
• Function: The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C. TAF3 forms the TFIID-A module together with TAF5 and TBP. Required in complex with TBPL2 for the differentiation of myoblasts into myocytes. The TAF3-TBPL2 complex replaces TFIID at specific promoters at an early stage in the differentiation process.
• 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)
  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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Josamycin	DMKJ8LB	Approved	Transcription initiation factor TFIID subunit 3 (TAF3) affects the response to substance of Josamycin.	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[9]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcription initiation factor TFIID subunit 3 (TAF3).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transcription initiation factor TFIID subunit 3 (TAF3).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Transcription initiation factor TFIID subunit 3 (TAF3).	[13]

References

• [1] Silencing of CD40 invivo reduces progression of experimental atherogenesis through an NF-B/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis.Atherosclerosis. 2016 Dec;255:80-89. doi: 10.1016/j.atherosclerosis.2016.11.002. Epub 2016 Nov 2.
• [2] 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.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [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] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [9] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.