Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIAM1A3)

• DOT Name: Nucleoplasmin-3 (NPM3)
• Gene Name: NPM3
• Related Disease:
  Alzheimer disease
  B-cell lymphoma
  Lung adenocarcinoma
  Neoplasm
  Parkinson disease
• UniProt ID: NPM3_HUMAN
• Pfam ID: PF03066
• Sequence:
  MAAGTAAALAFLSQESRTRAGGVGGLRVPAPVTMDSFFFGCELSGHTRSFTFKVEEEDDA
  EHVLALTMLCLTEGAKDECNVVEVVARNHDHQEIAVPVANLKLSCQPMLSLDDFQLQPPV
  TFRLKSGSGPVRITGRHQIVTMSNDVSEEESEEEEEDSDEEEVELCPILPAKKQGGRP
• Function: Plays a role in the regulation of diverse cellular processes such as ribosome biogenesis, chromatin remodeling or protein chaperoning. Modulates the histone chaperone function and the RNA-binding activity of nucleolar phosphoprotein B23/NPM. Efficiently mediates chromatin remodeling when included in a pentamer containing NPM3 and NPM.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[2]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Limited	Altered Expression	[4]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Nucleoplasmin-3 (NPM3).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleoplasmin-3 (NPM3).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleoplasmin-3 (NPM3).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nucleoplasmin-3 (NPM3).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nucleoplasmin-3 (NPM3).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Nucleoplasmin-3 (NPM3).	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Nucleoplasmin-3 (NPM3).	[13]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of Nucleoplasmin-3 (NPM3).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Nucleoplasmin-3 (NPM3).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nucleoplasmin-3 (NPM3).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nucleoplasmin-3 (NPM3).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nucleoplasmin-3 (NPM3).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Nucleoplasmin-3 (NPM3).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Nucleoplasmin-3 (NPM3).	[17]

References

• [1] Altered Machinery of Protein Synthesis in Alzheimer's: From the Nucleolus to the Ribosome.Brain Pathol. 2016 Sep;26(5):593-605. doi: 10.1111/bpa.12335. Epub 2015 Dec 14.
• [2] Clinical quantitation of diagnostic and predictive gene expression levels in follicular and diffuse large B-cell lymphoma by RT-PCR gene expression profiling.Blood. 2007 May 1;109(9):3922-8. doi: 10.1182/blood-2006-09-046391. Epub 2007 Jan 25.
• [3] c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
• [4] Genes affected by mouse mammary tumor virus (MMTV) proviral insertions in mouse mammary tumors are deregulated or mutated in primary human mammary tumors.Oncotarget. 2012 Nov;3(11):1320-34. doi: 10.18632/oncotarget.682.
• [5] Altered machinery of protein synthesis is region- and stage-dependent and is associated with -synuclein oligomers in Parkinson's disease.Acta Neuropathol Commun. 2015 Dec 1;3:76. doi: 10.1186/s40478-015-0257-4.
• [6] 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.
• [7] 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.
• [8] 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.
• [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] 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.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [14] Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
• [15] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [16] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [17] 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.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.