Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE56C5T)

• DOT Name: N-alpha-acetyltransferase 30 (NAA30)
• Synonyms: EC 2.3.1.256; N-acetyltransferase 12; N-acetyltransferase MAK3 homolog; NatC catalytic subunit
• Gene Name: NAA30
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
• UniProt ID: NAA30_HUMAN
• PDB ID: 7MX2; 7RB3
• EC Number: 2.3.1.256
• Pfam ID: PF00583
• Sequence:
  MAEVPPGPSSLLPPPAPPAPAAVEPRCPFPAGAALACCSEDEEDDEEHEGGGSRSPAGGE
  SATVAAKGHPCLRCPQPPQEQQQLNGLISPELRHLRAAASLKSKVLSVAEVAATTATPDG
  GPRATATKGAGVHSGERPPHSLSSNARTAVPSPVEAAAASDPAAARNGLAEGTEQEEEEE
  DEQVRLLSSSLTADCSLRSPSGREVEPGEDRTIRYVRYESELQMPDIMRLITKDLSEPYS
  IYTYRYFIHNWPQLCFLAMVGEECVGAIVCKLDMHKKMFRRGYIAMLAVDSKYRRNGIGT
  NLVKKAIYAMVEGDCDEVVLETEITNKSALKLYENLGFVRDKRLFRYYLNGVDALRLKLW
  LR
• Function: Catalytic subunit of the N-terminal acetyltransferase C (NatC) complex. Catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Leu-Ala and Met-Leu-Gly. Necessary for the lysosomal localization and function of ARL8B sugeesting that ARL8B is a NatC substrate.
• Reactome Pathway: Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
• BioCyc Pathway: MetaCyc:ENSG00000139977-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[1]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of N-alpha-acetyltransferase 30 (NAA30).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of N-alpha-acetyltransferase 30 (NAA30).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of N-alpha-acetyltransferase 30 (NAA30).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of N-alpha-acetyltransferase 30 (NAA30).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of N-alpha-acetyltransferase 30 (NAA30).	[6]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of N-alpha-acetyltransferase 30 (NAA30).	[6]

References

• [1] Knockdown of NAT12/NAA30 reduces tumorigenic features of glioblastoma-initiating cells.Mol Cancer. 2015 Aug 21;14:160. doi: 10.1186/s12943-015-0432-z.
• [2] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [3] 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.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [6] 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.