Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT48AES1)

• DOT Name: NHS-like protein 3 (NHSL3)
• Gene Name: NHSL3
• UniProt ID: NHSL3_HUMAN
• Pfam ID: PF15273
• Sequence:
  MVVFVGRRLPALLGLFKKKGSAKAENDKHLSVGPGQGPGSAVDEHQDNVFFPSGRPPHLE
  ELHTQAQEGLRSLQHQEKQKLNKGGWDHGDTQSIQSSRTGPDEDNISFCSQTTSYVAESS
  TAEDALSIRSEMIQRKGSTFRPHDSFPKSGKSGRRRRERRSTVLGLPQHVQKELGLRNER
  EAPGTPRAPGARDAVRIPTVDGRPRGTSGMGARVSLQALEAEAEAGAETEAMLQRHIDRV
  YRDDTFVGRSTGTRAPPLTRPMSLAVPGLTGGAGPAEPLSPAMSISPQATYLSKLIPHAV
  LPPTVDVVALGRCSLRTLSRCSLHSASPASVRSLGRFSSVSSPQPRSRHPSSSSDTWSHS
  QSSDTIVSDGSTLSSKGGSEGQPESSTASNSVVPPPQGGSGRGSPSGGSTAEASDTLSIR
  SSGQLSGRSVSLRKLKRPPPPPRRTHSLHQRGLAVPDGPLGLPPKPERKQQPQLPRPPTT
  GGSEGAGAAPCPPNPANSWVPGLSPGGSRRPPRSPERTLSPSSGYSSQSGTPTLPPKGLA
  GPPASPGKAQPPKPERVTSLRSPGASVSSSLTSLCSSSSDPAPSDRSGPQILTPLGDRFV
  IPPHPKVPAPFSPPPSKPRSPNPAAPALAAPAVVPGPVSTTDASPQSPPTPQTTLTPLQE
  SPVISKDQSPPPSPPPSYHPPPPPTKKPEVVVEAPSASETAEEPLQDPNWPPPPPPAPEE
  QDLSMADFPPPEEAFFSVASPEPAGPSGSPELVSSPAASSSSATALQIQPPGSPDPPPAP
  PAPAPASSAPGHVAKLPQKEPVGCSKGGGPPREDVGAPLVTPSLLQMVRLRSVGAPGGAP
  TPALGPSAPQKPLRRALSGRASPVPAPSSGLHAAVRLKACSLAASEGLSSAQPNGPPEAE
  PRPPQSPASTASFIFSKGSRKLQLERPVSPETQADLQRNLVAELRSISEQRPPQAPKKSP
  KAPPPVARKPSVGVPPPASPSYPRAEPLTAPPTNGLPHTQDRTKRELAENGGVLQLVGPE
  EKMGLPGSDSQKELA
• Function: Able to directly activate the TNF-NFkappaB signaling pathway.
• Tissue Specificity: Expressed in lung.

Molecular Interaction Atlas (MIA) of This DOT

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 NHS-like protein 3 (NHSL3).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of NHS-like protein 3 (NHSL3).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of NHS-like protein 3 (NHSL3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of NHS-like protein 3 (NHSL3).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of NHS-like protein 3 (NHSL3).	[4]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of NHS-like protein 3 (NHSL3).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of NHS-like protein 3 (NHSL3).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of NHS-like protein 3 (NHSL3).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of NHS-like protein 3 (NHSL3).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of NHS-like protein 3 (NHSL3).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of NHS-like protein 3 (NHSL3).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of NHS-like protein 3 (NHSL3).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of NHS-like protein 3 (NHSL3).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of NHS-like protein 3 (NHSL3).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of NHS-like protein 3 (NHSL3).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of NHS-like protein 3 (NHSL3).	[14]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [6] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] 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.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] 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.
• [14] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.