Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3BZWO8)

• DOT Name: E3 ubiquitin-protein ligase NEURL1B (NEURL1B)
• Synonyms: EC 2.3.2.27; Neuralized-2; NEUR2; Neuralized-like protein 1B; Neuralized-like protein 3; RING-type E3 ubiquitin transferase NEURL1B
• Gene Name: NEURL1B
• UniProt ID: NEU1B_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF07177 ; PF13920
• Sequence:
  MGNTVHRTLPDPSPPARLLATRPCCGPGPERRPVLGEAPRFHAQAKGKNVRLDGHSRRAT
  RRNSFCNGVTFTQRPIRLYEQVRLRLVAVRPGWSGALRFGFTAHDPSLMSAQDIPKYACP
  DLVTRPGYWAKALPENLALRDTVLAYWADRHGRVFYSVNDGEPVLFHCGVAVGGPLWALI
  DVYGITDEVQLLESAFADTLTPARLSQARFSACLPPSSHDAANFDNNELENNQVVAKLGH
  LALGRAPGPPPADAAAAAIPCGPRERPRPASSPALLEADLRFHATRGPDVSLSADRKVAC
  APRPDGGRTLVFSERPLRPGESLFVEVGRPGLAAPGALAFGITSCDPGVLRPNELPADPD
  ALLDRKEYWVVARAGPVPSGGDALSFTLRPGGDVLLGINGRPRGRLLCVDTTQALWAFFA
  VRGGVAGQLRLLGTLQSSPATTTPSGSLSGSQDDSDSDMTFSVNQSSSASESSLVTAPSS
  PLSPPVSPVFSPPEPAGIKNGECTVCFDGEVDTVIYTCGHMCLCHSCGLRLKRQARACCP
  ICRRPIKDVIKIYRP
• Function: E3 ubiquitin-protein ligase involved in regulation of the Notch pathway through influencing the stability and activity of several Notch ligands.
• Tissue Specificity: Highest expression in brain, prostate and small intestine. In the brain the levels are higher in fetal than in adult stage. In the adult brain the highest levels are detected in the olfactory system, cerebellar cortex, optic nerve and the frontal lobe.
• Reactome Pathway:
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD Domain Mutants (R-HSA-2691232)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  NOTCH2 Activation and Transmission of Signal to the Nucleus (R-HSA-2979096)
  NOTCH3 Activation and Transmission of Signal to the Nucleus (R-HSA-9013507)
  Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948)

Molecular Interaction Atlas (MIA) of This DOT

11 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 E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[3]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[4]
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[12]

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 E3 ubiquitin-protein ligase NEURL1B (NEURL1B).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Differently expressed long noncoding RNAs and mRNAs in TK6 cells exposed to low dose hydroquinone. Oncotarget. 2017 Oct 4;8(56):95554-95567. doi: 10.18632/oncotarget.21481. eCollection 2017 Nov 10.
• [5] NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
• [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] 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] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.