Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF4Q6ZW)

• DOT Name: Nucleosome assembly protein 1-like 5 (NAP1L5)
• Synonyms: Down-regulated in liver malignancy
• Gene Name: NAP1L5
• Related Disease:
  Advanced cancer
  Obesity
• UniProt ID: NP1L5_HUMAN
• Pfam ID: PF00956
• Sequence:
  MADSENQGPAEPSQAAAAAEAAAEEVMAEGGAQGGDCDSAAGDPDSAAGQMAEEPQTPAE
  NAPKPKNDFIESLPNSVKCRVLALKKLQKRCDKIEAKFDKEFQALEKKYNDIYKPLLAKI
  QELTGEMEGCAWTLEGEEEEEEEYEDDEEEGEDEEEEEAAAEAAAGAKHDDAHAEMPDDA
  KK
• Tissue Specificity: Predominantly expressed in brain.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Strong	Genetic Variation	[2]

2 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 Nucleosome assembly protein 1-like 5 (NAP1L5).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nucleosome assembly protein 1-like 5 (NAP1L5).	[13]

16 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 Nucleosome assembly protein 1-like 5 (NAP1L5).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[9]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[10]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[18]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Nucleosome assembly protein 1-like 5 (NAP1L5).	[7]

References

• [1] Down-regulation of a novel gene, DRLM, in human liver malignancy from 4q22 that encodes a NAP-like protein.Gene. 2002 Aug 21;296(1-2):171-7. doi: 10.1016/s0378-1119(02)00855-7.
• [2] Large copy-number variations are enriched in cases with moderate to extreme obesity.Diabetes. 2010 Oct;59(10):2690-4. doi: 10.2337/db10-0192. Epub 2010 Jul 9.
• [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] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [11] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] 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.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.