Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHX77K8)

• DOT Name: Beta-1,4-galactosyltransferase 3 (B4GALT3)
• Synonyms: Beta-1,4-GalTase 3; Beta4Gal-T3; b4Gal-T3; EC 2.4.1.-; Beta-N-acetylglucosaminyl-glycolipid beta-1,4-galactosyltransferase; Beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase; EC 2.4.1.38; N-acetyllactosamine synthase; EC 2.4.1.90; Nal synthase; Neolactotriaosylceramide beta-1,4-galactosyltransferase; EC 2.4.1.275; UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 3; UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 3
• Gene Name: B4GALT3
• Related Disease:
  Bladder cancer
  Colorectal carcinoma
  Neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  OPTN-related open angle glaucoma
  Advanced cancer
  Cervical cancer
  Cervical carcinoma
  Neuroblastoma
• UniProt ID: B4GT3_HUMAN
• EC Number: 2.4.1.-; 2.4.1.275; 2.4.1.38; 2.4.1.90
• Pfam ID: PF02709 ; PF13733
• Sequence:
  MLRRLLERPCTLALLVGSQLAVMMYLSLGGFRSLSALFGRDQGPTFDYSHPRDVYSNLSH
  LPGAPGGPPAPQGLPYCPERSPLLVGPVSVSFSPVPSLAEIVERNPRVEPGGRYRPAGCE
  PRSRTAIIVPHRAREHHLRLLLYHLHPFLQRQQLAYGIYVIHQAGNGTFNRAKLLNVGVR
  EALRDEEWDCLFLHDVDLLPENDHNLYVCDPRGPRHVAVAMNKFGYSLPYPQYFGGVSAL
  TPDQYLKMNGFPNEYWGWGGEDDDIATRVRLAGMKISRPPTSVGHYKMVKHRGDKGNEEN
  PHRFDLLVRTQNSWTQDGMNSLTYQLLARELGPLYTNITADIGTDPRGPRAPSGPRYPPG
  SSQAFRQEMLQRRPPARPGPLSTANHTALRGSH
• Function: Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids.
• Tissue Specificity: Found in various tissues. Highest expression in placenta, prostate, testis, ovary, intestine and muscle, and in fetal brain.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Various types of N-glycan biosynthesis (hsa00513)
  Other types of O-glycan biosynthesis (hsa00514)
  Mannose type O-glycan biosynthesis (hsa00515)
  Glycosaminoglycan biosynthesis - keratan sulfate (hsa00533)
  Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  N-Glycan antennae elongation (R-HSA-975577)
  Keratan sulfate biosynthesis (R-HSA-2022854)
• BioCyc Pathway: MetaCyc:HS08336-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]
OPTN-related open angle glaucoma	DISDR98A	Disputed	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]
Cervical cancer	DISFSHPF	Limited	Biomarker	[4]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[4]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[5]

8 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 Beta-1,4-galactosyltransferase 3 (B4GALT3).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Beta-1,4-galactosyltransferase 3 (B4GALT3).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Beta-1,4-galactosyltransferase 3 (B4GALT3).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Beta-1,4-galactosyltransferase 3 (B4GALT3).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Beta-1,4-galactosyltransferase 3 (B4GALT3).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Beta-1,4-galactosyltransferase 3 (B4GALT3).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Beta-1,4-galactosyltransferase 3 (B4GALT3).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Beta-1,4-galactosyltransferase 3 (B4GALT3).	[13]

References

• [1] Circular RNA circUBXN7 represses cell growth and invasion by sponging miR-1247-3p to enhance B4GALT3 expression in bladder cancer.Aging (Albany NY). 2018 Oct 12;10(10):2606-2623. doi: 10.18632/aging.101573.
• [2] -1,4-Galactosyltransferase III suppresses 1 integrin-mediated invasive phenotypes and negatively correlates with metastasis in colorectal cancer.Carcinogenesis. 2014 Jun;35(6):1258-66. doi: 10.1093/carcin/bgu007. Epub 2014 Jan 8.
• [3] Identification of Mutations in Myocilin and Beta-1,4-galactosyltransferase 3 Genes in a Chinese Family with Primary Open-angle Glaucoma.Chin Med J (Engl). 2016 Dec 5;129(23):2810-2815. doi: 10.4103/0366-6999.194641.
• [4] B4GALT3 up-regulation by miR-27a contributes to the oncogenic activity in human cervical cancer cells.Cancer Lett. 2016 Jun 1;375(2):284-292. doi: 10.1016/j.canlet.2016.03.016. Epub 2016 Mar 14.
• [5] -1,4-Galactosyltransferase III enhances invasive phenotypes via 1-integrin and predicts poor prognosis in neuroblastoma.Clin Cancer Res. 2013 Apr 1;19(7):1705-16. doi: 10.1158/1078-0432.CCR-12-2367. Epub 2013 Feb 26.
• [6] 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.
• [7] 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.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.