Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUEF3PL)

• DOT Name: Probable N-acetyltransferase 14 (NAT14)
• Synonyms: EC 2.3.1.-; K562 cell-derived leucine-zipper-like protein 1
• Gene Name: NAT14
• UniProt ID: NAT14_HUMAN
• EC Number: 2.3.1.-
• Pfam ID: PF00583
• Sequence:
  MAPSHLSVREMREDEKPLVLEMLKAGVKDTENRVALHALTRPPALLLLAAASSGLRFVLA
  SFALALLLPVFLAVAAVKLGLRARWGSLPPPGGLGGPWVAVRGSGDVCGVLALAPGTNAG
  DGARVTRLSVSRWHRRRGVGRRLLAFAEARARAWAGGMGEPRARLVVPVAVAAWGVGGML
  EGCGYQAEGGWGCLGYTLVREFSKDL
• Function: Probable acetyltransferase; May act as a transcription factor that regulates the expression of coproporphyrinogen oxidase by binding to a promoter regulatory element.
• Tissue Specificity: Expressed in K-562 and HeLa cell lines and in brain.

Molecular Interaction Atlas (MIA) of This DOT

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 Probable N-acetyltransferase 14 (NAT14).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Probable N-acetyltransferase 14 (NAT14).	[6]

6 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 Probable N-acetyltransferase 14 (NAT14).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Probable N-acetyltransferase 14 (NAT14).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Probable N-acetyltransferase 14 (NAT14).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Probable N-acetyltransferase 14 (NAT14).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Probable N-acetyltransferase 14 (NAT14).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Probable N-acetyltransferase 14 (NAT14).	[8]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] 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.
• [6] 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.
• [7] 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.
• [8] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.