Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI8VWK3)

• DOT Name: N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38)
• Synonyms: LSM domain-containing protein 1; Phosphonoformate immuno-associated protein 2
• Gene Name: NAA38
• Related Disease: Cardiovascular disease
• UniProt ID: LSMD1_HUMAN
• PDB ID: 7MX2
• Pfam ID: PF01423
• Sequence:
  MAGAGPTMLLREENGCCSRRQSSSSAGDSDGEREDSAAERARQQLEALLNKTMRIRMTDG
  RTLVGCFLCTDRDCNVILGSAQEFLKPSDSFSAGEPRVLGLAMVPGHHIVSIEVQRESLT
  GPPYL
• Function: Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues.
• Reactome Pathway: Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
• BioCyc Pathway: MetaCyc:G66-33018-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]

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 N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38).	[9]

7 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 N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38).	[7]
Aspirin	DM672AH	Approved	Aspirin increases the expression of N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of N-alpha-acetyltransferase 38, NatC auxiliary subunit (NAA38).	[10]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.