Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOAZJ55)

• DOT Name: Zinc finger protein AEBP2 (AEBP2)
• Synonyms: Adipocyte enhancer-binding protein 2; AE-binding protein 2
• Gene Name: AEBP2
• Related Disease:
  Acute myelogenous leukaemia
  Hirschsprung disease
• UniProt ID: AEBP2_HUMAN
• PDB ID: 5WAI; 5Y0U; 5Y1U; 6C23; 6C24; 6WKR; 7KSO; 8FYH
• Sequence:
  MAAAITDMADLEELSRLSPLPPGSPGSAARGRAEPPEEEEEEEEEEEEAEAEAVAALLLN
  GGSGGGGGGGGGGVGGGEAETMSEPSPESASQAGEDEDEEEDDEEEEDESSSSGGGEEES
  SAESLVGSSGGSSSDETRSLSPGAASSSSGDGDGKEGLEEPKGPRGSQGGGGGGSSSSSV
  VSSGGDEGYGTGGGGSSATSGGRRGSLEMSSDGEPLSRMDSEDSISSTIMDVDSTISSGR
  STPAMMNGQGSTTSSSKNIAYNCCWDQCQACFNSSPDLADHIRSIHVDGQRGGVFVCLWK
  GCKVYNTPSTSQSWLQRHMLTHSGDKPFKCVVGGCNASFASQGGLARHVPTHFSQQNSSK
  VSSQPKAKEESPSKAGMNKRRKLKNKRRRSLPRPHDFFDAQTLDAIRHRAICFNLSAHIE
  SLGKGHSVVFHSTVIAKRKEDSGKIKLLLHWMPEDILPDVWVNESERHQLKTKVVHLSKL
  PKDTALLLDPNIYRTMPQKRLKRTLIRKVFNLYLSKQ
• Function: Acts as an accessory subunit for the core Polycomb repressive complex 2 (PRC2), which mediates histone H3K27 (H3K27me3) trimethylation on chromatin leading to transcriptional repression of the affected target gene. Plays a role in nucleosome localization of the PRC2 complex.
• KEGG Pathway: Polycomb repressive complex (hsa03083)
• Reactome Pathway:
  PKMTs methylate histone lysines (R-HSA-3214841)
  PRC2 methylates histones and DNA (R-HSA-212300)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[1]
Hirschsprung disease	DISUUSM1	Strong	Biomarker	[2]

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 Zinc finger protein AEBP2 (AEBP2).	[3]
Selenium	DM25CGV	Approved	Selenium decreases the methylation of Zinc finger protein AEBP2 (AEBP2).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Zinc finger protein AEBP2 (AEBP2).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Zinc finger protein AEBP2 (AEBP2).	[9]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Zinc finger protein AEBP2 (AEBP2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Zinc finger protein AEBP2 (AEBP2).	[4]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Zinc finger protein AEBP2 (AEBP2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Zinc finger protein AEBP2 (AEBP2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Zinc finger protein AEBP2 (AEBP2).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Zinc finger protein AEBP2 (AEBP2).	[10]

References

• [1] The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by single nucleotide polymorphism array and exon sequencing of 100 candidate genes.Br J Haematol. 2016 Jul;174(2):292-301. doi: 10.1111/bjh.14056. Epub 2016 Mar 28.
• [2] Aebp2 as an epigenetic regulator for neural crest cells.PLoS One. 2011;6(9):e25174. doi: 10.1371/journal.pone.0025174. Epub 2011 Sep 19.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Epigenetic assessment of environmental chemicals detected in maternal peripheral and cord blood samples. J Reprod Dev. 2011 Sep;57(4):507-17. doi: 10.1262/jrd.11-034a. Epub 2011 May 23.
• [6] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [7] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] 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.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [11] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.