Details of Drug Off-Target (DOT)

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

• DOT Name: N-alpha-acetyltransferase 35, NatC auxiliary subunit (NAA35)
• Synonyms: Embryonic growth-associated protein homolog; Protein MAK10 homolog
• Gene Name: NAA35
• Related Disease:
  Candidemia
  Esophageal squamous cell carcinoma
• UniProt ID: NAA35_HUMAN
• PDB ID: 7MX2; 7RB3
• Pfam ID: PF04112
• Sequence:
  MVMKASVDDDDSGWELSMPEKMEKSNTNWVDITQDFEEACRELKLGELLHDKLFGLFEAM
  SAIEMMDPKMDAGMIGNQVNRKVLNFEQAIKDGTIKIKDLTLPELIGIMDTCFCCLITWL
  EGHSLAQTVFTCLYIHNPDFIEDPAMKAFALGILKICDIAREKVNKAAVFEEEDFQSMTY
  GFKMANSVTDLRVTGMLKDVEDDMQRRVKSTRSRQGEERDPEVELEHQQCLAVFSRVKFT
  RVLLTVLIAFTKKETSAVAEAQKLMVQAADLLSAIHNSLHHGIQAQNDTTKGDHPIMMGF
  EPLVNQRLLPPTFPRYAKIIKREEMVNYFARLIDRIKTVCEVVNLTNLHCILDFFCEFSE
  QSPCVLSRSLLQTTFLVDNKKVFGTHLMQDMVKDALRSFVSPPVLSPKCYLYNNHQAKDC
  IDSFVTHCVRPFCSLIQIHGHNRARQRDKLGHILEEFATLQDEAEKVDAALHTMLLKQEP
  QRQHLACLGTWVLYHNLRIMIQYLLSGFELELYSMHEYYYIYWYLSEFLYAWLMSTLSRA
  DGSQMAEERIMEEQQKGRSSKKTKKKKKVRPLSREITMSQAYQNMCAGMFKTMVAFDMDG
  KVRKPKFELDSEQVRYEHRFAPFNSVMTPPPVHYLQFKEMSDLNKYSPPPQSPELYVAAS
  KHFQQAKMILENIPNPDHEVNRILKVAKPNFVVMKLLAGGHKKESKVPPEFDFSAHKYFP
  VVKLV
• Function: Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues. Involved in regulation of apoptosis and proliferation of smooth muscle cells.
• Reactome Pathway: Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
• BioCyc Pathway: MetaCyc:ENSG00000135040-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
Candidemia	DISVKFN7	Strong	Genetic Variation	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of N-alpha-acetyltransferase 35, NatC auxiliary subunit (NAA35).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-alpha-acetyltransferase 35, NatC auxiliary subunit (NAA35).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of N-alpha-acetyltransferase 35, NatC auxiliary subunit (NAA35).	[5]

2 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 35, NatC auxiliary subunit (NAA35).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of N-alpha-acetyltransferase 35, NatC auxiliary subunit (NAA35).	[7]

References

• [1] Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi.Nat Med. 2016 Aug;22(8):952-60. doi: 10.1038/nm.4139. Epub 2016 Jul 4.
• [2] Aberrant chimeric RNA GOLM1-MAK10 encoding a secreted fusion protein as a molecular signature for human esophageal squamous cell carcinoma.Oncotarget. 2013 Nov;4(11):2135-43. doi: 10.18632/oncotarget.1465.
• [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] 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.
• [6] 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.
• [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.