Details of Drug Off-Target (DOT)

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

• DOT Name: Chromatin modification-related protein MEAF6 (MEAF6)
• Synonyms: MYST/Esa1-associated factor 6; Esa1-associated factor 6 homolog; Protein EAF6 homolog; hEAF6; Sarcoma antigen NY-SAR-91
• Gene Name: MEAF6
• Related Disease:
  Lung cancer
  Neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: EAF6_HUMAN
• Pfam ID: PF09340
• Sequence:
  MAMHNKAAPPQIPDTRRELAELVKRKQELAETLANLERQIYAFEGSYLEDTQMYGNIIRG
  WDRYLTNQKNSNSKNDRRNRKFKEAERLFSKSSVTSAAAVSALAGVQDQLIEKREPGSGT
  ESDTSPDFHNQENEPSQEDPEDLDGSVQGVKPQKAASSTSSGSHHSSHKKRKNKNRHRID
  LKLNKKPRADY
• Function: Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)
• Reactome Pathway:
  Regulation of TP53 Activity through Acetylation (R-HSA-6804758)
  HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Limited	Altered Expression	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Prostate cancer	DISF190Y	Limited	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[1]

8 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 Chromatin modification-related protein MEAF6 (MEAF6).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Chromatin modification-related protein MEAF6 (MEAF6).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Chromatin modification-related protein MEAF6 (MEAF6).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Chromatin modification-related protein MEAF6 (MEAF6).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chromatin modification-related protein MEAF6 (MEAF6).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Chromatin modification-related protein MEAF6 (MEAF6).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Chromatin modification-related protein MEAF6 (MEAF6).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Chromatin modification-related protein MEAF6 (MEAF6).	[10]

References

• [1] Alternative RNA splicing of the MEAF6 gene facilitates neuroendocrine prostate cancer progression.Oncotarget. 2017 Apr 25;8(17):27966-27975. doi: 10.18632/oncotarget.15854.
• [2] MEAF6/PHF1 is a recurrent gene fusion in endometrial stromal sarcoma.Cancer Lett. 2014 May 28;347(1):75-8. doi: 10.1016/j.canlet.2014.01.030. Epub 2014 Feb 11.
• [3] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] 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.
• [8] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.