Details of Drug Off-Target (DOT)

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

DOT Name Transcription initiation factor TFIID subunit 4 (TAF4)
Synonyms
RNA polymerase II TBP-associated factor subunit C; TBP-associated factor 4; Transcription initiation factor TFIID 130 kDa subunit; TAF(II)130; TAFII-130; TAFII130; Transcription initiation factor TFIID 135 kDa subunit; TAF(II)135; TAFII-135; TAFII135
Gene Name TAF4
Related Disease
Acute myelogenous leukaemia ( )
Dentatorubral-pallidoluysian atrophy ( )
Huntington disease ( )
Myocardial infarction ( )
Spinocerebellar ataxia type 3 ( )
UniProt ID
TAF4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1H3O; 2P6V; 6MZC; 6MZD; 6MZL; 6MZM; 7EDX; 7EG7; 7EG8; 7EG9; 7EGA; 7EGB; 7EGC; 7EGD; 7EGE; 7EGF; 7EGG; 7EGI; 7EGJ; 7ENA; 7ENC; 8GXQ; 8GXS; 8WAK; 8WAL; 8WAN; 8WAO; 8WAP; 8WAQ; 8WAR; 8WAS
Pfam ID
PF05236 ; PF07531
Sequence
MAAGSDLLDEVFFNSEVDEKVVSDLVGSLESQLAASAAHHHHLAPRTPEVRAAAAGALGN
HVVSGSPAGAAGAGPAAPAEGAPGAAPEPPPAGRARPGGGGPQRPGPPSPRRPLVPAGPA
PPAAKLRPPPEGSAGSCAPVPAAAAVAAGPEPAPAGPAKPAGPAALAARAGPGPGPGPGP
GPGPGPGKPAGPGAAQTLNGSAALLNSHHAAAPAVSLVNNGPAALLPLPKPAAPGTVIQT
PPFVGAAAPPAPAAPSPPAAPAPAAPAAAPPPPPPAPATLARPPGHPAGPPTAAPAVPPP
AAAQNGGSAGAAPAPAPAAGGPAGVSGQPGPGAAAAAPAPGVKAESPKRVVQAAPPAAQT
LAASGPASTAASMVIGPTMQGALPSPAAVPPPAPGTPTGLPKGAAGAVTQSLSRTPTATT
SGIRATLTPTVLAPRLPQPPQNPTNIQNFQLPPGMVLVRSENGQLLMIPQQALAQMQAQA
HAQPQTTMAPRPATPTSAPPVQISTVQAPGTPIIARQVTPTTIIKQVSQAQTTVQPSATL
QRSPGVQPQLVLGGAAQTASLGTATAVQTGTPQRTVPGATTTSSAATETMENVKKCKNFL
STLIKLASSGKQSTETAANVKELVQNLLDGKIEAEDFTSRLYRELNSSPQPYLVPFLKRS
LPALRQLTPDSAAFIQQSQQQPPPPTSQATTALTAVVLSSSVQRTAGKTAATVTSALQPP
VLSLTQPTQVGVGKQGQPTPLVIQQPPKPGALIRPPQVTLTQTPMVALRQPHNRIMLTTP
QQIQLNPLQPVPVVKPAVLPGTKALSAVSAQAAAAQKNKLKEPGGGSFRDDDDINDVASM
AGVNLSEESARILATNSELVGTLTRSCKDETFLLQAPLQRRILEIGKKHGITELHPDVVS
YVSHATQQRLQNLVEKISETAQQKNFSYKDDDRYEQASDVRAQLKFFEQLDQIEKQRKDE
QEREILMRAAKSRSRQEDPEQLRLKQKAKEMQQQELAQMRQRDANLTALAAIGPRKKRKV
DCPGPGSGAEGSGPGSVVPGSSGVGTPRQFTRQRITRVNLRDLIFCLENERETSHSLLLY
KAFLK
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. TAF4 may maintain an association between the TFIID and TFIIA complexes, while bound to the promoter, together with TBP, during PIC assembly. Potentiates transcriptional activation by the AF-2S of the retinoic acid, vitamin D3 and thyroid hormone.
KEGG Pathway
Basal transcription factors (hsa03022 )
Huntington disease (hsa05016 )
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

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [1]
Dentatorubral-pallidoluysian atrophy DISHWE0K Strong Biomarker [2]
Huntington disease DISQPLA4 Strong Biomarker [3]
Myocardial infarction DIS655KI Strong Genetic Variation [4]
Spinocerebellar ataxia type 3 DISQBQID Strong Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 4 (TAF4) affects the response to substance of Josamycin. [15]
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5 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 4 (TAF4). [5]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the methylation of Transcription initiation factor TFIID subunit 4 (TAF4). [6]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Transcription initiation factor TFIID subunit 4 (TAF4). [11]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Transcription initiation factor TFIID subunit 4 (TAF4). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Transcription initiation factor TFIID subunit 4 (TAF4). [13]
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5 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 TFIID subunit 4 (TAF4). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Transcription initiation factor TFIID subunit 4 (TAF4). [8]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Transcription initiation factor TFIID subunit 4 (TAF4). [9]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Transcription initiation factor TFIID subunit 4 (TAF4). [10]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Transcription initiation factor TFIID subunit 4 (TAF4). [14]
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References

1 A TFIID-SAGA Perturbation that Targets MYB and Suppresses Acute Myeloid Leukemia.Cancer Cell. 2018 Jan 8;33(1):13-28.e8. doi: 10.1016/j.ccell.2017.12.002.
2 Pathology of CAG repeat diseases.Neuropathology. 2000 Dec;20(4):319-25. doi: 10.1046/j.1440-1789.2000.00354.x.
3 Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease.Science. 2002 Jun 21;296(5576):2238-43. doi: 10.1126/science.1072613. Epub 2002 May 2.
4 Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
5 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.
6 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
7 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
8 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.
9 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
10 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.
11 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.
12 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.
13 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
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.