Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCTH3C6)

• DOT Name: Transcription initiation factor TFIID subunit 9 (TAF9)
• Synonyms: RNA polymerase II TBP-associated factor subunit G; STAF31/32; Transcription initiation factor TFIID 31 kDa subunit; TAFII-31; TAFII31; Transcription initiation factor TFIID 32 kDa subunit; TAFII-32; TAFII32
• Gene Name: TAF9
• Related Disease:
  Hepatocellular carcinoma
  HIV infectious disease
  Testicular cancer
  Schizophrenia
• UniProt ID: TAF9_HUMAN
• PDB ID: 6F3T; 6MZC; 6MZD; 6MZL; 6MZM; 7EDX; 7EG7; 7EG8; 7EG9; 7EGA; 7EGB; 7EGC; 7EGD; 7EGE; 7EGF; 7EGG; 7EGI; 7EGJ; 7ENA; 7ENC; 8GXQ; 8GXS; 8H7G; 8WAK; 8WAL; 8WAN; 8WAO; 8WAP; 8WAQ; 8WAR; 8WAS
• Pfam ID: PF02291
• Sequence:
  MESGKTASPKSMPKDAQMMAQILKDMGITEYEPRVINQMLEFAFRYVTTILDDAKIYSSH
  AKKATVDADDVRLAIQCRADQSFTSPPPRDFLLDIARQRNQTPLPLIKPYSGPRLPPDRY
  CLTAPNYRLKSLQKKASTSAGRITVPRLSVGSVTSRPSTPTLGTPTPQTMSVSTKVGTPM
  SLTGQRFTVQMPTSQSPAVKASIPATSAVQNVLINPSLIGSKNILITTNMMSSQNTANES
  SNALKRKREDDDDDDDDDDDYDNL
• 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. TAF9 is also a component of the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TAF9 and its paralog TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. Essential for cell viability. May have a role in gene regulation associated with apoptosis.
• 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 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)
  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
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
HIV infectious disease	DISO97HC	Strong	Biomarker	[2]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	No Known	Unknown	[4]

3 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 TFIID subunit 9 (TAF9).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Transcription initiation factor TFIID subunit 9 (TAF9).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Transcription initiation factor TFIID subunit 9 (TAF9).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription initiation factor TFIID subunit 9 (TAF9).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription initiation factor TFIID subunit 9 (TAF9).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transcription initiation factor TFIID subunit 9 (TAF9).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Transcription initiation factor TFIID subunit 9 (TAF9).	[7]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Transcription initiation factor TFIID subunit 9 (TAF9).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Transcription initiation factor TFIID subunit 9 (TAF9).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Transcription initiation factor TFIID subunit 9 (TAF9).	[12]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Transcription initiation factor TFIID subunit 9 (TAF9).	[13]
GW7604	DMCA4RM	Investigative	GW7604 increases the expression of Transcription initiation factor TFIID subunit 9 (TAF9).	[14]

References

• [1] A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection.Gastroenterology. 2013 Jul;145(1):176-187. doi: 10.1053/j.gastro.2013.03.051. Epub 2013 Apr 6.
• [2] Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.J Virol. 2004 Sep;78(17):9458-73. doi: 10.1128/JVI.78.17.9458-9473.2004.
• [3] Cancertestis antigen HCA587/MAGEC2 interacts with the general transcription coactivator TAF9 in cancer cells.Mol Med Rep. 2018 Feb;17(2):3226-3231. doi: 10.3892/mmr.2017.8260. Epub 2017 Dec 12.
• [4] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [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] 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.
• [7] Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
• [8] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [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.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [13] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [14] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.