Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQNA67C)

DOT Name Cell growth-regulating nucleolar protein (LYAR)
Gene Name LYAR
Related Disease
Medulloblastoma ( )
Neuroblastoma ( )
UniProt ID
LYAR_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6ZMI; 6ZMO; 6ZVH
Pfam ID
PF17848 ; PF08790
Sequence
MVFFTCNACGESVKKIQVEKHVSVCRNCECLSCIDCGKDFWGDDYKNHVKCISEDQKYGG
KGYEGKTHKGDIKQQAWIQKISELIKRPNVSPKVRELLEQISAFDNVPRKKAKFQNWMKN
SLKVHNESILDQVWNIFSEASNSEPVNKEQDQRPLHPVANPHAEISTKVPASKVKDAVEQ
QGEVKKNKRERKEERQKKRKREKKELKLENHQENSRNQKPKKRKKGQEADLEAGGEEVPE
ANGSAGKRSKKKKQRKDSASEEEARVGAGKRKRRHSEVETDSKKKKMKLPEHPEGGEPED
DEAPAKGKFNWKGTIKAILKQAPDNEITIKKLRKKVLAQYYTVTDEHHRSEEELLVIFNK
KISKNPTFKLLKDKVKLVK
Function
Plays a role in the maintenance of the appropriate processing of 47S/45S pre-rRNA to 32S/30S pre-rRNAs and their subsequent processing to produce 18S and 28S rRNAs. Also acts at the level of transcription regulation. Along with PRMT5, binds the gamma-globin (HBG1/HBG2) promoter and represses its expression. In neuroblastoma cells, may also repress the expression of oxidative stress genes, including CHAC1, HMOX1, SLC7A11, ULBP1 and SNORD41 that encodes a small nucleolar RNA. Preferentially binds to a DNA motif containing 5'-GGTTAT-3'. Negatively regulates the antiviral innate immune response by targeting IRF3 and impairing its DNA-binding activity. In addition, inhibits NF-kappa-B-mediated expression of pro-inflammatory cytokines. Stimulates phagocytosis of photoreceptor outer segments by retinal pigment epithelial cells. Prevents nucleolin/NCL self-cleavage, maintaining a normal steady-state level of NCL protein in undifferentiated embryonic stem cells (ESCs), which in turn is essential for ESC self-renewal.
Tissue Specificity Predominantly expressed in testis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Medulloblastoma DISZD2ZL Strong Biomarker [1]
Neuroblastoma DISVZBI4 Limited Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
17 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 Cell growth-regulating nucleolar protein (LYAR). [3]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Cell growth-regulating nucleolar protein (LYAR). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Cell growth-regulating nucleolar protein (LYAR). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Cell growth-regulating nucleolar protein (LYAR). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Cell growth-regulating nucleolar protein (LYAR). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Cell growth-regulating nucleolar protein (LYAR). [8]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Cell growth-regulating nucleolar protein (LYAR). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Cell growth-regulating nucleolar protein (LYAR). [10]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Cell growth-regulating nucleolar protein (LYAR). [10]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Cell growth-regulating nucleolar protein (LYAR). [11]
Menadione DMSJDTY Approved Menadione affects the expression of Cell growth-regulating nucleolar protein (LYAR). [9]
Ethanol DMDRQZU Approved Ethanol decreases the expression of Cell growth-regulating nucleolar protein (LYAR). [12]
GSK2110183 DMZHB37 Phase 2 GSK2110183 decreases the expression of Cell growth-regulating nucleolar protein (LYAR). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Cell growth-regulating nucleolar protein (LYAR). [14]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Cell growth-regulating nucleolar protein (LYAR). [16]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Cell growth-regulating nucleolar protein (LYAR). [18]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Cell growth-regulating nucleolar protein (LYAR). [20]
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⏷ Show the Full List of 17 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Cell growth-regulating nucleolar protein (LYAR). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Cell growth-regulating nucleolar protein (LYAR). [17]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Cell growth-regulating nucleolar protein (LYAR). [19]
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References

1 Mutations in Lyar and p53 are synergistically lethal in female mice.Birth Defects Res A Clin Mol Teratol. 2012 Sep;94(9):729-37. doi: 10.1002/bdra.23048. Epub 2012 Jul 19.
2 Upregulation of LYAR induces neuroblastoma cell proliferation and survival.Cell Death Differ. 2017 Sep;24(9):1645-1654. doi: 10.1038/cdd.2017.98. Epub 2017 Jul 7.
3 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.
4 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.
5 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
6 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
7 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
8 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.
9 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.
10 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
11 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
12 Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
13 Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
14 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
15 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
16 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.
17 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
18 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
19 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
20 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.