Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLWR71Z)

• DOT Name: N-alpha-acetyltransferase 80 (NAA80)
• Synonyms: HsNAAA80; EC 2.3.1.-; N-acetyltransferase 6; Protein fusion-2; Protein fus-2
• Gene Name: NAA80
• Related Disease:
  Advanced cancer
  Malignant tumor of nasopharynx
  Neoplasm
• UniProt ID: NAA80_HUMAN
• PDB ID: 6NAS; 6NBE; 6NBW
• EC Number: 2.3.1.-
• Pfam ID: PF00583
• Sequence:
  MELILSTSPAELTLDPACQPKLPLDSTCQPEMTFNPGPTELTLDPEHQPEETPAPSLAEL
  TLEPVHRRPELLDACADLINDQWPRSRTSRLHSLGQSSDAFPLCLMLLSPHPTLEAAPVV
  VGHARLSRVLNQPQSLLVETVVVARALRGRGFGRRLMEGLEVFARARGFRKLHLTTHDQV
  HFYTHLGYQLGEPVQGLVFTSRRLPATLLNAFPTAPSPRPPRKAPNLTAQAAPRGPKGPP
  LPPPPPLPECLTISPPVPSGPPSKSLLETQYQNVRGRPIFWMEKDI
• Function: N-alpha-acetyltransferase that specifically mediates the acetylation of the acidic amino terminus of processed forms of beta- and gamma-actin (ACTB and ACTG, respectively). N-terminal acetylation of processed beta- and gamma-actin regulates actin filament depolymerization and elongation. In vivo, preferentially displays N-terminal acetyltransferase activity towards acid N-terminal sequences starting with Asp-Asp-Asp and Glu-Glu-Glu. In vitro, shows high activity towards Met-Asp-Glu-Leu and Met-Asp-Asp-Asp. May act as a tumor suppressor.
• Tissue Specificity: Strongly expressed in heart and skeletal muscle, followed by brain and pancreas, with weak expression in kidney, liver, and lung and no expression in placenta.
• BioCyc Pathway: MetaCyc:MONOMER66-43060

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[1]
Malignant tumor of nasopharynx	DISTGIGF	moderate	Genetic Variation	[1]
Neoplasm	DISZKGEW	moderate	Biomarker	[1]

9 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 80 (NAA80).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of N-alpha-acetyltransferase 80 (NAA80).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-alpha-acetyltransferase 80 (NAA80).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of N-alpha-acetyltransferase 80 (NAA80).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of N-alpha-acetyltransferase 80 (NAA80).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of N-alpha-acetyltransferase 80 (NAA80).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of N-alpha-acetyltransferase 80 (NAA80).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of N-alpha-acetyltransferase 80 (NAA80).	[9]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of N-alpha-acetyltransferase 80 (NAA80).	[10]

References

• [1] Characterization of a new SNP c767A/T (Arg222Trp) in the candidate TSG FUS2 on human chromosome 3p21.3: prevalence in Asian populations and analysis of association with nasopharyngeal cancer.Mol Cell Probes. 2004 Feb;18(1):39-44. doi: 10.1016/j.mcp.2003.09.002.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [9] Bortezomib induces caspase-dependent apoptosis in Hodgkin lymphoma cell lines and is associated with reduced c-FLIP expression: a gene expression profiling study with implications for potential combination therapies. Leuk Res. 2008 Feb;32(2):275-85. doi: 10.1016/j.leukres.2007.05.024. Epub 2007 Jul 19.
• [10] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.