Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVT1Q25)

• DOT Name: N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3)
• Synonyms: EC 2.4.1.149; Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase; EC 2.4.1.146; Beta-1,3-galactosyltransferase 8; Beta-1,3-GalTase 8; Beta3Gal-T8; Beta3GalT8; b3Gal-T8; Beta-3-Gx-T8; Core 1 extending beta-1,3-N-acetylglucosaminyltransferase; Core1-beta3GlcNAcT; Transmembrane protein 3; UDP-Gal:beta-GlcNAc beta-1,3-galactosyltransferase 8; UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3; BGnT-3; Beta-1,3-Gn-T3; Beta-1,3-N-acetylglucosaminyltransferase 3; Beta3Gn-T3; UDP-galactose:beta-N-acetylglucosamine beta-1,3-galactosyltransferase 8
• Gene Name: B3GNT3
• Related Disease:
  Advanced cancer
  Influenza
  Non-small-cell lung cancer
  Triple negative breast cancer
  Neoplasm
  Cervical cancer
  Cervical carcinoma
  Human papillomavirus infection
  Neuroblastoma
• UniProt ID: B3GN3_HUMAN
• EC Number: 2.4.1.146; 2.4.1.149
• Pfam ID: PF01762
• Sequence:
  MKYLRHRRPNATLILAIGAFTLLLFSLLVSPPTCKVQEQPPAIPEALAWPTPPTRPAPAP
  CHANTSMVTHPDFATQPQHVQNFLLYRHCRHFPLLQDVPPSKCAQPVFLLLVIKSSPSNY
  VRRELLRRTWGRERKVRGLQLRLLFLVGTASNPHEARKVNRLLELEAQTHGDILQWDFHD
  SFFNLTLKQVLFLQWQETRCANASFVLNGDDDVFAHTDNMVFYLQDHDPGRHLFVGQLIQ
  NVGPIRAFWSKYYVPEVVTQNERYPPYCGGGGFLLSRFTAAALRRAAHVLDIFPIDDVFL
  GMCLELEGLKPASHSGIRTSGVRAPSQRLSSFDPCFYRDLLLVHRFLPYEMLLMWDALNQ
  PNLTCGNQTQIY
• Function: Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Has activity for type 2 oligosaccharides. Also acts as a core1-1,3-N-acetylglucosaminyltransferase (Core1-beta3GlcNAcT) to form the 6-sulfo sialyl Lewis x on extended core1 O-glycans.
• Tissue Specificity: Expressed in colon, jejunum, stomach, esophagus, placenta and trachea.
• KEGG Pathway:
  Mucin type O-glycan biosynthesis (hsa00512)
  Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  O-linked glycosylation of mucins (R-HSA-913709)
  Keratan sulfate biosynthesis (R-HSA-2022854)
• BioCyc Pathway: MetaCyc:ENSG00000179913-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Influenza	DIS3PNU3	Strong	Genetic Variation	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[5]
Cervical cancer	DISFSHPF	Limited	Biomarker	[1]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[1]
Human papillomavirus infection	DISX61LX	Limited	Altered Expression	[1]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[6]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) decreases the response to substance of Arsenic trioxide.	[15]
Methotrexate	DM2TEOL	Approved	N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) affects the response to substance of Methotrexate.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3).	[14]

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 increases the methylation of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3).	[12]

References

• [1] B3GNT3 Expression Is a Novel Marker Correlated with Pelvic Lymph Node Metastasis and Poor Clinical Outcome in Early-Stage Cervical Cancer.PLoS One. 2015 Dec 28;10(12):e0144360. doi: 10.1371/journal.pone.0144360. eCollection 2015.
• [2] Interferon-Inducible Transmembrane Protein 3 Genetic Variant rs12252 and Influenza Susceptibility and Severity: A Meta-Analysis.PLoS One. 2015 May 5;10(5):e0124985. doi: 10.1371/journal.pone.0124985. eCollection 2015.
• [3] B3GNT3 overexpression is associated with unfavourable survival in non-small cell lung cancer.J Clin Pathol. 2018 Jul;71(7):642-647. doi: 10.1136/jclinpath-2017-204860. Epub 2018 Feb 26.
• [4] Eradication of Triple-Negative Breast Cancer Cells by Targeting Glycosylated PD-L1.Cancer Cell. 2018 Feb 12;33(2):187-201.e10. doi: 10.1016/j.ccell.2018.01.009.
• [5] Novel role of O-glycosyltransferases GALNT3 and B3GNT3 in the self-renewal of pancreatic cancer stem cells.BMC Cancer. 2018 Nov 22;18(1):1157. doi: 10.1186/s12885-018-5074-2.
• [6] B3GNT3 expression suppresses cell migration and invasion and predicts favorable outcomes in neuroblastoma.Cancer Sci. 2013 Dec;104(12):1600-8. doi: 10.1111/cas.12294. Epub 2013 Oct 28.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.
• [16] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.