Details of Drug Off-Target (DOT)

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

• DOT Name: Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E)
• Synonyms: LANP-like protein; LANP-L
• Gene Name: ANP32E
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
  Triple negative breast cancer
  Ulcerative colitis
• UniProt ID: AN32E_HUMAN
• PDB ID: 4CAY; 4NFT
• Pfam ID: PF14580
• Sequence:
  MEMKKKINLELRNRSPEEVTELVLDNCLCVNGEIEGLNDTFKELEFLSMANVELSSLARL
  PSLNKLRKLELSDNIISGGLEVLAEKCPNLTYLNLSGNKIKDLSTVEALQNLKNLKSLDL
  FNCEITNLEDYRESIFELLQQITYLDGFDQEDNEAPDSEEEDDEDGDEDDEEEEENEAGP
  PEGYEEEEEEEEEEDEDEDEDEDEAGSELGEGEEEVGLSYLMKEEIQDEEDDDDYVEEGE
  EEEEEEEGGLRGEKRKRDAEDDGEEEDD
• Function: Histone chaperone that specifically mediates the genome-wide removal of histone H2A.Z/H2AZ1 from the nucleosome: removes H2A.Z/H2AZ1 from its normal sites of deposition, especially from enhancer and insulator regions. Not involved in deposition of H2A.Z/H2AZ1 in the nucleosome. May stabilize the evicted H2A.Z/H2AZ1-H2B dimer, thus shifting the equilibrium towards dissociation and the off-chromatin state. Inhibits activity of protein phosphatase 2A (PP2A). Does not inhibit protein phosphatase 1. May play a role in cerebellar development and synaptogenesis.
• Tissue Specificity: Expressed in peripheral blood leukocytes, colon, small intestine, prostate, thymus, spleen, skeletal muscle, liver and kidney.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[1]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[2]

19 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 Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[11]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[20]

2 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 decreases the methylation of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[14]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E).	[16]

References

• [1] ANP32E induces tumorigenesis of triple-negative breast cancer cells by upregulating E2F1.Mol Oncol. 2018 Jun;12(6):896-912. doi: 10.1002/1878-0261.12202. Epub 2018 Apr 18.
• [2] ANP32E, a Protein Involved in Steroid-Refractoriness in Ulcerative Colitis, Identified by a Systems Biology Approach.J Crohns Colitis. 2019 Mar 26;13(3):351-361. doi: 10.1093/ecco-jcc/jjy171.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [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] 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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.