Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUEG3QY)

• DOT Name: Nucleosome assembly protein 1-like 4 (NAP1L4)
• Synonyms: Nucleosome assembly protein 2; NAP-2
• Gene Name: NAP1L4
• Related Disease:
  Alcohol dependence
  Childhood kidney Wilms tumor
  Wilms tumor
• UniProt ID: NP1L4_HUMAN
• Pfam ID: PF00956
• Sequence:
  MADHSFSDGVPSDSVEAAKNASNTEKLTDQVMQNPRVLAALQERLDNVPHTPSSYIETLP
  KAVKRRINALKQLQVRCAHIEAKFYEEVHDLERKYAALYQPLFDKRREFITGDVEPTDAE
  SEWHSENEEEEKLAGDMKSKVVVTEKAAATAEEPDPKGIPEFWFTIFRNVDMLSELVQEY
  DEPILKHLQDIKVKFSDPGQPMSFVLEFHFEPNDYFTNSVLTKTYKMKSEPDKADPFSFE
  GPEIVDCDGCTIDWKKGKNVTVKTIKKKQKHKGRGTVRTITKQVPNESFFNFFNPLKASG
  DGESLDEDSEFTLASDFEIGHFFRERIVPRAVLYFTGEAIEDDDNFEEGEEGEEEELEGD
  EEGEDEDDAEINPKV
• Function: Acts as a histone chaperone in nucleosome assembly.
• Tissue Specificity: Ubiquitous. Biallelically expressed in fetal and adult tissues. Highest levels in testis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[1]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Biomarker	[2]
Wilms tumor	DISB6T16	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Nucleosome assembly protein 1-like 4 (NAP1L4).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nucleosome assembly protein 1-like 4 (NAP1L4).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nucleosome assembly protein 1-like 4 (NAP1L4).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nucleosome assembly protein 1-like 4 (NAP1L4).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nucleosome assembly protein 1-like 4 (NAP1L4).	[9]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Nucleosome assembly protein 1-like 4 (NAP1L4).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Nucleosome assembly protein 1-like 4 (NAP1L4).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nucleosome assembly protein 1-like 4 (NAP1L4).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nucleosome assembly protein 1-like 4 (NAP1L4).	[14]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Nucleosome assembly protein 1-like 4 (NAP1L4).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Nucleosome assembly protein 1-like 4 (NAP1L4).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Nucleosome assembly protein 1-like 4 (NAP1L4).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Nucleosome assembly protein 1-like 4 (NAP1L4).	[12]

References

• [1] Genome-wide association study of alcohol dependence implicates a region on chromosome 11.Alcohol Clin Exp Res. 2010 May;34(5):840-52. doi: 10.1111/j.1530-0277.2010.01156.x. Epub 2010 Mar 1.
• [2] Functional characterization of human nucleosome assembly protein-2 (NAP1L4) suggests a role as a histone chaperone.Genomics. 1997 Sep 15;44(3):253-65. doi: 10.1006/geno.1997.4868.
• [3] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] 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.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [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] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [11] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [12] 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.
• [13] 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.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [15] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.