Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQZII5O)

• DOT Name: Transcription initiation factor TFIID subunit 12 (TAF12)
• Synonyms: Transcription initiation factor TFIID 20/15 kDa subunits; TAFII-20/TAFII-15; TAFII20/TAFII15
• Gene Name: TAF12
• Related Disease:
  Acute myelogenous leukaemia
  Familial amyotrophic lateral sclerosis
  Liposarcoma
  Malignant soft tissue neoplasm
  Sarcoma
  Neuroblastoma
• UniProt ID: TAF12_HUMAN
• PDB ID: 1H3O; 6MZC; 6MZD; 6MZL; 6MZM; 7EDX; 7EG7; 7EG8; 7EG9; 7EGA; 7EGB; 7EGC; 7EGD; 7EGE; 7EGF; 7EGG; 7EGI; 7EGJ; 7ENA; 7ENC; 7KTR; 7KTS; 8GXQ; 8GXS; 8H7G; 8WAK; 8WAL; 8WAN; 8WAO; 8WAP; 8WAQ; 8WAR; 8WAS
• Pfam ID: PF03847
• Sequence:
  MNQFGPSALINLSNFSSIKPEPASTPPQGSMANSTAVVKIPGTPGAGGRLSPENNQVLTK
  KKLQDLVREVDPNEQLDEDVEEMLLQIADDFIESVVTAACQLARHRKSSTLEVKDVQLHL
  ERQWNMWIPGFGSEEIRPYKKACTTEAHKQRMALIRKTTKK
• 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. Component of the TATA-binding protein-free TAF complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex.
• Tissue Specificity: Ubiquitous.
• 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)
  HATs acetylate histones (R-HSA-3214847)
  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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Genetic Variation	[2]
Liposarcoma	DIS8IZVM	Strong	Altered Expression	[2]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Genetic Variation	[2]
Sarcoma	DISZDG3U	Strong	Genetic Variation	[2]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcription initiation factor TFIID subunit 12 (TAF12).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription initiation factor TFIID subunit 12 (TAF12).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription initiation factor TFIID subunit 12 (TAF12).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transcription initiation factor TFIID subunit 12 (TAF12).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Transcription initiation factor TFIID subunit 12 (TAF12).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Transcription initiation factor TFIID subunit 12 (TAF12).	[6]

3 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 affects the methylation of Transcription initiation factor TFIID subunit 12 (TAF12).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Transcription initiation factor TFIID subunit 12 (TAF12).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Transcription initiation factor TFIID subunit 12 (TAF12).	[11]

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] mRNA and protein levels of FUS, EWSR1, and TAF15 are upregulated in liposarcoma.Genes Chromosomes Cancer. 2011 May;50(5):338-47. doi: 10.1002/gcc.20858. Epub 2011 Feb 22.
• [3] Histone deacetylase 1 gene expression and sensitization of multidrug-resistant neuroblastoma cell lines to cytotoxic agents by depsipeptide.J Natl Cancer Inst. 2007 Jul 18;99(14):1107-19. doi: 10.1093/jnci/djm044. Epub 2007 Jul 10.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] 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.
• [9] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [10] 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.
• [11] 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.