Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYWGHF1)

• DOT Name: Queuosine-tRNA galactosyltransferase (B3GNTL1)
• Synonyms: QTGAL; EC 2.4.1.-; Beta-1,3-N-acetylglucosaminyltransferase 8; BGnT-8; Beta-1,3-Gn-T8; Beta3Gn-T8; UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase-like protein 1; BGnT-like protein 1; Beta1,3-N-acetylglucosaminyltransferase-like protein 1; Beta3Gn-T-like protein 1; Beta3GnTL1
• Gene Name: B3GNTL1
• Related Disease:
  Lung cancer
  Lung carcinoma
  Myocardial infarction
  Colon cancer
  Colon carcinoma
  Dravet syndrome
  Neoplasm
  Psoriasis
  Rheumatoid arthritis
• UniProt ID: QTGAL_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF00535
• Sequence:
  MQAHVSIILPVHNAEPWLDECLRSVLQQDFEGTMELSVFNDASKDKSGAIIEKWRVKLED
  SGVHVIIGGHDSPSPRGVGYAKNQAVAQSSGSYLCFLDSDDVMMPQRVRLQHEAAVQHPS
  SIIGCRVRRDPPNSTERYTRWINQLTPEQLLTQVFTSNGPTVIMPTWFCSRAWFSHVGPF
  NEGGQGVPEDLLFFYEHLRKGGGVIRVDQSLLLYRHHPQAATHCVLETTIWTHRVRFLEE
  QALPRWAAFTIWNAGKQGRRLYRSLTAGSQRKVVAFCDVDENKIRKGFYCHEDSQERPKP
  RIPILHFRAARPPFVICVKLDLTGGAFEDNLRSLHLQEGQDFLHFS
• Function: Glycosyltransferase that specifically catalyzes galactosylation of cytoplasmic tRNA(Tyr) modified with queuosine at position 34 (queuosine(34)). Galactosylates the cyclopentene hydroxyl group of queuosine(34) in tRNA(Tyr) to form galactosyl-queuosine(34). Mannosylation of queuosine(34) in tRNA(Tyr) is required to slow-down elongation at cognate codons UAC and suppress stop codon readthrough, thereby regulating protein translation.
• Tissue Specificity: Widely expressed. Highly expressed in adult pancreas. Expressed at moderate level in kidney, spleen, thymus, prostate, testis and ovary. Weakly expressed in small intestine, colon, peripheral blood leukocyte and liver.
• Reactome Pathway: O-linked glycosylation of mucins (R-HSA-913709)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Genetic Variation	[1]
Lung carcinoma	DISTR26C	Definitive	Genetic Variation	[1]
Myocardial infarction	DIS655KI	Definitive	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[3]
Dravet syndrome	DISJF7LY	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Psoriasis	DIS59VMN	Strong	Altered Expression	[6]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[7]

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 Queuosine-tRNA galactosyltransferase (B3GNTL1).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Queuosine-tRNA galactosyltransferase (B3GNTL1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Queuosine-tRNA galactosyltransferase (B3GNTL1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Queuosine-tRNA galactosyltransferase (B3GNTL1).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Queuosine-tRNA galactosyltransferase (B3GNTL1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Queuosine-tRNA galactosyltransferase (B3GNTL1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Queuosine-tRNA galactosyltransferase (B3GNTL1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Queuosine-tRNA galactosyltransferase (B3GNTL1).	[15]

References

• [1] DNA methylation and associated gene expression in blood prior to lung cancer diagnosis in the Norwegian Women and Cancer cohort.Sci Rep. 2018 Nov 13;8(1):16714. doi: 10.1038/s41598-018-34334-6.
• [2] Association of polymorphisms of platelet membrane integrins alpha IIb(beta)3 (HPA-1b/Pl) and alpha2(beta)1 (alpha807TT) with premature myocardial infarction.J Thromb Haemost. 2005 Jul;3(7):1522-9. doi: 10.1111/j.1538-7836.2005.01432.x.
• [3] A novel beta1,3-N-acetylglucosaminyltransferase (beta3Gn-T8), which synthesizes poly-N-acetyllactosamine, is dramatically upregulated in colon cancer.FEBS Lett. 2005 Jan 3;579(1):71-8. doi: 10.1016/j.febslet.2004.11.037.
• [4] A homozygous mutation of voltage-gated sodium channel (I) gene SCN1B in a patient with Dravet syndrome.Epilepsia. 2012 Dec;53(12):e200-3. doi: 10.1111/epi.12040. Epub 2012 Nov 13.
• [5] 12-month patterns of serum markers of collagen synthesis, transforming growth factor and connective tissue growth factor are similar in new-onset and chronic dilated cardiomyopathy in patients both with and without cardiac fibrosis.Cytokine. 2017 Aug;96:217-227. doi: 10.1016/j.cyto.2017.04.021. Epub 2017 Apr 28.
• [6] Abnormality of RUNX1 signal transduction in psoriatic CD34+ bone marrow cells.Br J Dermatol. 2011 May;164(5):1043-51. doi: 10.1111/j.1365-2133.2010.10192.x.
• [7] A new look at the shared epitope hypothesis.Am J Med. 1988 Dec 23;85(6A):20-2. doi: 10.1016/0002-9343(88)90375-0.
• [8] 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.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [15] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.