Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJB0VA6)

• DOT Name: N-alpha-acetyltransferase 20 (NAA20)
• Synonyms: EC 2.3.1.254; Methionine N-acetyltransferase; N-acetyltransferase 5; N-terminal acetyltransferase B complex catalytic subunit NAA20; N-terminal acetyltransferase B complex catalytic subunit NAT5; NatB complex subunit NAT5; NatB catalytic subunit
• Gene Name: NAA20
• Related Disease: Intellectual developmental disorder, autosomal recessive 73
• UniProt ID: NAA20_HUMAN
• PDB ID: 6VP9; 7STX; 8G0L
• EC Number: 2.3.1.254
• Pfam ID: PF00583
• Sequence:
  MTTLRAFTCDDLFRFNNINLDPLTETYGIPFYLQYLAHWPEYFIVAEAPGGELMGYIMGK
  AEGSVAREEWHGHVTALSVAPEFRRLGLAAKLMELLEEISERKGGFFVDLFVRVSNQVAV
  NMYKQLGYSVYRTVIEYYSASNGEPDEDAYDMRKALSRDTEKKSIIPLPHPVRPEDIE
• Function: Catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln. Proteins with cell cycle functions are overrepresented in the pool of NatB substrates. Required for maintaining the structure and function of actomyosin fibers and for proper cellular migration.
• BioCyc Pathway: MetaCyc:HS10662-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
Intellectual developmental disorder, autosomal recessive 73	DISA6RCK	Strong	Autosomal recessive	[1]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Isoniazid	DM5JVS3	Approved	N-alpha-acetyltransferase 20 (NAA20) increases the Hepatotoxicity ADR of Isoniazid.	[8]
Reserpine	DM6VM38	Approved	N-alpha-acetyltransferase 20 (NAA20) increases the Systemic lupus erythematosus ADR of Reserpine.	[8]
Procainamide	DMNMXR8	Approved	N-alpha-acetyltransferase 20 (NAA20) increases the Systemic lupus erythematosus ADR of Procainamide.	[8]
Dapsone	DM4LT8A	Approved	N-alpha-acetyltransferase 20 (NAA20) increases the Hypersensitivity ADR of Dapsone.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of N-alpha-acetyltransferase 20 (NAA20).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of N-alpha-acetyltransferase 20 (NAA20).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of N-alpha-acetyltransferase 20 (NAA20).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of N-alpha-acetyltransferase 20 (NAA20).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of N-alpha-acetyltransferase 20 (NAA20).	[7]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of N-alpha-acetyltransferase 20 (NAA20).	[5]

References

• [1] Missense NAA20 variants impairing the NatB protein N-terminal acetyltransferase cause autosomal recessive developmental delay, intellectual disability, and microcephaly. Genet Med. 2021 Nov;23(11):2213-2218. doi: 10.1038/s41436-021-01264-0. Epub 2021 Jul 6.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] 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.
• [6] 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.
• [7] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [8] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.