Details of Drug Off-Target (DOT)

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

• DOT Name: N-alpha-acetyltransferase 40 (NAA40)
• Synonyms: EC 2.3.1.257; N-acetyltransferase 11; N-alpha-acetyltransferase D; NatD; hNatD; Protein acetyltransferase 1
• Gene Name: NAA40
• Related Disease:
  Hepatocellular carcinoma
  Neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Lung cancer
  Lung carcinoma
• UniProt ID: NAA40_HUMAN
• PDB ID: 4U9V; 4U9W; 7KD7; 7KPU
• EC Number: 2.3.1.257
• Pfam ID: PF00583
• Sequence:
  MGRKSSKAKEKKQKRLEERAAMDAVCAKVDAANRLGDPLEAFPVFKKYDRNGLNVSIECK
  RVSGLEPATVDWAFDLTKTNMQTMYEQSEWGWKDREKREEMTDDRAWYLIAWENSSVPVA
  FSHFRFDVECGDEVLYCYEVQLESKVRRKGLGKFLIQILQLMANSTQMKKVMLTVFKHNH
  GAYQFFREALQFEIDDSSPSMSGCCGEDCSYEILSRRTKFGDSHHSHAGGHCGGCCH
• Function: N-alpha-acetyltransferase that specifically mediates the acetylation of the N-terminal residues of histones H4 and H2A. In contrast to other N-alpha-acetyltransferase, has a very specific selectivity for histones H4 and H2A N-terminus and specifically recognizes the 'Ser-Gly-Arg-Gly sequence'. Acts as a negative regulator of apoptosis. May play a role in hepatic lipid metabolism.
• Tissue Specificity: Widely expressed; with the highest expression level in liver and the lowest expression in brain (at protein level).
• BioCyc Pathway: MetaCyc:ENSG00000110583-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Colon cancer	DISVC52G	Limited	Biomarker	[2]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[2]
Lung cancer	DISCM4YA	Limited	Biomarker	[3]
Lung carcinoma	DISTR26C	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of N-alpha-acetyltransferase 40 (NAA40).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of N-alpha-acetyltransferase 40 (NAA40).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-alpha-acetyltransferase 40 (NAA40).	[6]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of N-alpha-acetyltransferase 40 (NAA40).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of N-alpha-acetyltransferase 40 (NAA40).	[7]

References

• [1] Patt1, a novel protein acetyltransferase that is highly expressed in liver and downregulated in hepatocellular carcinoma, enhances apoptosis of hepatoma cells.Int J Biochem Cell Biol. 2009 Dec;41(12):2528-37. doi: 10.1016/j.biocel.2009.08.009. Epub 2009 Aug 18.
• [2] NAA40 contributes to colorectal cancer growth by controlling PRMT5 expression.Cell Death Dis. 2019 Mar 11;10(3):236. doi: 10.1038/s41419-019-1487-3.
• [3] NatD promotes lung cancer progression by preventing histone H4 serine phosphorylation to activate Slug expression.Nat Commun. 2017 Oct 13;8(1):928. doi: 10.1038/s41467-017-00988-5.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] 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.
• [8] Ochratoxin a lowers mRNA levels of genes encoding for key proteins of liver cell metabolism. Cancer Genomics Proteomics. 2008 Nov-Dec;5(6):319-32.