Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT59OKEJ)

• DOT Name: Mediator of RNA polymerase II transcription subunit 9 (MED9)
• Synonyms: Mediator complex subunit 9
• Gene Name: MED9
• Related Disease:
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hereditary hemochromatosis
  Prostate cancer
  Prostate carcinoma
• UniProt ID: MED9_HUMAN
• PDB ID: 7EMF; 7ENA; 7ENC; 7ENJ; 7LBM; 7NVR; 8GXQ; 8GXS
• Pfam ID: PF07544
• Sequence:
  MASAGVAAGRQAEDVLPPTSDQPLPDTKPLPPPQPPPVPAPQPQQSPAPRPQSPARAREE
  ENYSFLPLVHNIIKCMDKDSPEVHQDLNALKSKFQEMRKLISTMPGIHLSPEQQQQQLQS
  LREQVRTKNELLQKYKSLCMFEIPKE
• Function: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
• Reactome Pathway:
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[2]
Hereditary hemochromatosis	DISVG5MT	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Mediator of RNA polymerase II transcription subunit 9 (MED9).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mediator of RNA polymerase II transcription subunit 9 (MED9).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Mediator of RNA polymerase II transcription subunit 9 (MED9).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Mediator of RNA polymerase II transcription subunit 9 (MED9).	[8]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Mediator of RNA polymerase II transcription subunit 9 (MED9).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mediator of RNA polymerase II transcription subunit 9 (MED9).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Mediator of RNA polymerase II transcription subunit 9 (MED9).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Mediator of RNA polymerase II transcription subunit 9 (MED9).	[11]

References

• [1] Clinical significance of a highly sensitive enzyme immunoassay of hepatitis B surface antigen using a novel electron spin resonance technique.J Med Virol. 2002 Feb;66(2):166-70. doi: 10.1002/jmv.2126.
• [2] In vitro-targeted gene identification in patients with hepatitis C using a genome-wide microarray technology.Hepatology. 2009 Feb;49(2):378-86. doi: 10.1002/hep.22677.
• [3] ETV4 and AP1 Transcription Factors Form Multivalent Interactions with three Sites on the MED25 Activator-Interacting Domain.J Mol Biol. 2017 Oct 13;429(20):2975-2995. doi: 10.1016/j.jmb.2017.06.024. Epub 2017 Jul 17.
• [4] Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] 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.
• [10] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [11] 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.