Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT14W6UW)

• DOT Name: Nucleolar protein 4-like (NOL4L)
• Gene Name: NOL4L
• Related Disease:
  Childhood acute lymphoblastic leukemia
  Chronic obstructive pulmonary disease
• UniProt ID: NOL4L_HUMAN
• Sequence:
  MSDSTWMSADPHLASSLSPSQDERMRSPQNLHSQEDDDSSSESGSGNGSSTLNPSTSSST
  QGDPAFPEMNGNGAVAPMDFTTAAEDQPINLCDKLPPATALGTASYPSDGCGADGLRSRV
  KYGVKTTPESPPYSSGSYDSIKTEVSGCPEDLTVGRAPTADDDDDDHDDHEDNDKMNDSE
  GMDPERLKAFNMFVRLFVDENLDRMVPISKQPKEKIQAIIESCSRQFPEFQERARKRIRT
  YLKSCRRMKKNGMEMTRPTPPHLTSAMAENILAAACESETRKAAKRMRLEIYQSSQDEPI
  ALDKQHSRDSAAITHSTYSLPASSYSQDPVYANGGLNYSYRGYGALSSNLQPPASLQTGN
  HSNGPTDLSMKGGASTTSTTPTPTPSSTSTSRPVPTAQLSPTEISAVRQLIAGYRESAAF
  LLRSADELENLILQQN

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]

6 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 Nucleolar protein 4-like (NOL4L).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Nucleolar protein 4-like (NOL4L).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Nucleolar protein 4-like (NOL4L).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Nucleolar protein 4-like (NOL4L).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nucleolar protein 4-like (NOL4L).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Nucleolar protein 4-like (NOL4L).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleolar protein 4-like (NOL4L).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nucleolar protein 4-like (NOL4L).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nucleolar protein 4-like (NOL4L).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nucleolar protein 4-like (NOL4L).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nucleolar protein 4-like (NOL4L).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Nucleolar protein 4-like (NOL4L).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Nucleolar protein 4-like (NOL4L).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nucleolar protein 4-like (NOL4L).	[10]
Marinol	DM70IK5	Approved	Marinol increases the expression of Nucleolar protein 4-like (NOL4L).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nucleolar protein 4-like (NOL4L).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nucleolar protein 4-like (NOL4L).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nucleolar protein 4-like (NOL4L).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nucleolar protein 4-like (NOL4L).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nucleolar protein 4-like (NOL4L).	[19]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Nucleolar protein 4-like (NOL4L).	[20]

References

• [1] Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray.Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11921-6. doi: 10.1073/pnas.0711039105. Epub 2008 Aug 12.
• [2] Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.Nat Genet. 2017 Mar;49(3):426-432. doi: 10.1038/ng.3752. Epub 2017 Feb 6.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] 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.
• [11] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] 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.
• [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] 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.
• [19] 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.
• [20] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.