Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8P1FP6)

• DOT Name: N-acylglucosamine 2-epimerase (RENBP)
• Synonyms: AGE; EC 5.1.3.8; GlcNAc 2-epimerase; N-acetyl-D-glucosamine 2-epimerase; Renin-binding protein; RnBP
• Gene Name: RENBP
• UniProt ID: RENBP_HUMAN
• EC Number: 5.1.3.8
• Pfam ID: PF07221
• Sequence:
  MSKGLPARQDMEKERETLQAWKERVGQELDRVVAFWMEHSHDQEHGGFFTCLGREGRVYD
  DLKYVWLQGRQVWMYCRLYRTFERFRHAQLLDAAKAGGEFLLRYARVAPPGKKCAFVLTR
  DGRPVKVQRTIFSECFYTMAMNELWRATGEVRYQTEAVEMMDQIVHWVQEDASGLGRPQL
  QGAPAAEPMAVPMMLLNLVEQLGEADEELAGKYAELGDWCARRILQHVQRDGQAVLENVS
  EGGKELPGCLGRQQNPGHTLEAGWFLLRHCIRKGDPELRAHVIDKFLLLPFHSGWDPDHG
  GLFYFQDADNFCPTQLEWAMKLWWPHSEAMIAFLMGYSDSGDPVLLRLFYQVAEYTFRQF
  RDPEYGEWFGYLSREGKVALSIKGGPFKGCFHVPRCLAMCEEMLGALLSRPAPAPSPAPT
  PACRGAE
• Function: Catalyzes the interconversion of N-acetylglucosamine to N-acetylmannosamine. Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway: although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded.
• KEGG Pathway:
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of UDP-N-acetyl-glucosamine (R-HSA-446210)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of N-acylglucosamine 2-epimerase (RENBP).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of N-acylglucosamine 2-epimerase (RENBP).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of N-acylglucosamine 2-epimerase (RENBP).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of N-acylglucosamine 2-epimerase (RENBP).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of N-acylglucosamine 2-epimerase (RENBP).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of N-acylglucosamine 2-epimerase (RENBP).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of N-acylglucosamine 2-epimerase (RENBP).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of N-acylglucosamine 2-epimerase (RENBP).	[3]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the expression of N-acylglucosamine 2-epimerase (RENBP).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of N-acylglucosamine 2-epimerase (RENBP).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of N-acylglucosamine 2-epimerase (RENBP).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of N-acylglucosamine 2-epimerase (RENBP).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of N-acylglucosamine 2-epimerase (RENBP).	[12]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of N-acylglucosamine 2-epimerase (RENBP).	[13]

References

• [1] 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.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Methamphetamine alters the normal progression by inducing cell cycle arrest in astrocytes. PLoS One. 2014 Oct 7;9(10):e109603.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [11] 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.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [13] In Vitro Exposure of Human Luteinized Mural Granulosa Cells to Dibutyl Phthalate Affects Global Gene Expression. Toxicol Sci. 2017 Nov 1;160(1):180-188. doi: 10.1093/toxsci/kfx170.