Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT27A1MS)

• DOT Name: Beta-citrylglutamate synthase B (RIMKLB)
• Synonyms: EC 6.3.1.17; N-acetyl-aspartylglutamate synthetase B; NAAG synthetase B; NAAGS; EC 6.3.2.41; Ribosomal protein S6 modification-like protein B
• Gene Name: RIMKLB
• UniProt ID: RIMKB_HUMAN
• EC Number: 6.3.1.17; 6.3.2.41
• Pfam ID: PF08443
• Sequence:
  MCSSVAAKLWFLTDRRIREDYPQKEILRALKAKCCEEELDFRAVVMDEVVLTIEQGNLGL
  RINGELITAYPQVVVVRVPTPWVQSDSDITVLRHLEKMGCRLMNRPQAILNCVNKFWTFQ
  ELAGHGVPLPDTFSYGGHENFAKMIDEAEVLEFPMVVKNTRGHRGKAVFLARDKHHLADL
  SHLIRHEAPYLFQKYVKESHGRDVRVIVVGGRVVGTMLRCSTDGRMQSNCSLGGVGMMCS
  LSEQGKQLAIQVSNILGMDVCGIDLLMKDDGSFCVCEANANVGFIAFDKACNLDVAGIIA
  DYAASLLPSGRLTRRMSLLSVVSTASETSEPELGPPASTAVDNMSASSSSVDSDPESTER
  ELLTKLPGGLFNMNQLLANEIKLLVD
• Function: Catalyzes the synthesis of beta-citryl-L-glutamate and N-acetyl-L-aspartyl-L-glutamate. Beta-citryl-L-glutamate is synthesized more efficiently than N-acetyl-L-aspartyl-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

12 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 Beta-citrylglutamate synthase B (RIMKLB).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Beta-citrylglutamate synthase B (RIMKLB).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Beta-citrylglutamate synthase B (RIMKLB).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Beta-citrylglutamate synthase B (RIMKLB).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Beta-citrylglutamate synthase B (RIMKLB).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Beta-citrylglutamate synthase B (RIMKLB).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Beta-citrylglutamate synthase B (RIMKLB).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Beta-citrylglutamate synthase B (RIMKLB).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Beta-citrylglutamate synthase B (RIMKLB).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Beta-citrylglutamate synthase B (RIMKLB).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Beta-citrylglutamate synthase B (RIMKLB).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Beta-citrylglutamate synthase B (RIMKLB).	[13]

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 affects the methylation of Beta-citrylglutamate synthase B (RIMKLB).	[8]

References

• [1] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.
• [10] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [12] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.