Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9JSU8L)

• DOT Name: Nucleoplasmin-2 (NPM2)
• Gene Name: NPM2
• Related Disease: Melanoma
• UniProt ID: NPM2_HUMAN
• PDB ID: 3T30
• Pfam ID: PF03066
• Sequence:
  MNLSSASSTEEKAVTTVLWGCELSQERRTWTFRPQLEGKQSCRLLLHTICLGEKAKEEMH
  RVEILPPANQEDKKMQPVTIASLQASVLPMVSMVGVQLSPPVTFQLRAGSGPVFLSGQER
  YEASDLTWEEEEEEEGEEEEEEEEDDEDEDADISLEEQSPVKQVKRLVPQKQASVAKKKK
  LEKEEEEIRASVRDKSPVKKAKATARAKKPGFKK
• Function: Core histones chaperone involved in chromatin reprogramming, specially during fertilization and early embryonic development. Probably involved in sperm DNA decondensation during fertilization.
• Reactome Pathway: Replacement of protamines by nucleosomes in the male pronucleus (R-HSA-9821993)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]

4 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 Nucleoplasmin-2 (NPM2).	[2]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Nucleoplasmin-2 (NPM2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nucleoplasmin-2 (NPM2).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Nucleoplasmin-2 (NPM2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleoplasmin-2 (NPM2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nucleoplasmin-2 (NPM2).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Nucleoplasmin-2 (NPM2).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Nucleoplasmin-2 (NPM2).	[9]

References

• [1] Gene Expression and Methylation Analysis in Melanomas and Melanocytes From the Same Patient: Loss of NPM2 Expression Is a Potential Immunohistochemical Marker for Melanoma.Front Oncol. 2019 Jan 21;8:675. doi: 10.3389/fonc.2018.00675. eCollection 2018.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [6] Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia. Blood. 2008 Feb 15;111(4):2382-4. doi: 10.1182/blood-2007-07-103960. Epub 2007 Nov 30.
• [7] 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.
• [8] 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.
• [9] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.