Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHO71W8)

• DOT Name: N-acetylaspartylglutamate synthase A (RIMKLA)
• Synonyms: NAAG synthetase A; NAAGS; EC 6.3.2.41; N-acetylaspartylglutamylglutamate synthase A; EC 6.3.2.42; Ribosomal protein S6 modification-like protein A
• Gene Name: RIMKLA
• UniProt ID: RIMKA_HUMAN
• EC Number: 6.3.2.41; 6.3.2.42
• Pfam ID: PF08443
• Sequence:
  MCSQLWFLTDRRIREDYPQVQILRALRQRCSEQDVRFRAVLMDQIAVTIVGGHLGLQLNQ
  KALTTFPDVVLVRVPTPSVQSDSDITVLRHLEKLGCRLVNRPQSILNCINKFWTFQELAG
  HGVPMPDTFSYGGHEDFSKMIDEAEPLGYPVVVKSTRGHRGKAVFLARDKHHLSDICHLI
  RHDVPYLFQKYVKESHGKDIRVVVVGGQVIGSMLRCSTDGRMQSNCSLGGVGVKCPLTEQ
  GKQLAIQVSNILGMDFCGIDLLIMDDGSFVVCEANANVGFLAFDQACNLDVGGIIADYTM
  SLLPNRQTGKMAVLPGLSSPREKNEPDGCASAQGVAESVYTINSGSTSSESEPELGEIRD
  SSASTMGAPPSMLPEPGYNINNRIASELKLK
• Function: Catalyzes the synthesis of N-acetyl-L-aspartyl-L-glutamate (NAAG) and N-acetyl-L-aspartyl-L-glutamyl-L-glutamate.
• KEGG Pathway:
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Glutamate and glutamine metabolism (R-HSA-8964539)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of N-acetylaspartylglutamate synthase A (RIMKLA).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-acetylaspartylglutamate synthase A (RIMKLA).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of N-acetylaspartylglutamate synthase A (RIMKLA).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of N-acetylaspartylglutamate synthase A (RIMKLA).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of N-acetylaspartylglutamate synthase A (RIMKLA).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of N-acetylaspartylglutamate synthase A (RIMKLA).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of N-acetylaspartylglutamate synthase A (RIMKLA).	[8]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of N-acetylaspartylglutamate synthase A (RIMKLA).	[9]

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 increases the methylation of N-acetylaspartylglutamate synthase A (RIMKLA).	[7]

References

• [1] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.