Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8GFSQL)

• DOT Name: UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1)
• Synonyms: Beta-1,3-GalNAc-T1; EC 2.4.1.79; Beta-1,3-galactosyltransferase 3; Beta-1,3-GalTase 3; Beta3Gal-T3; Beta3GalT3; b3Gal-T3; Beta-3-Gx-T3; Galactosylgalactosylglucosylceramide beta-D-acetyl-galactosaminyltransferase; Globoside synthase; UDP-N-acetylgalactosamine:globotriaosylceramide beta-1,3-N-acetylgalactosaminyltransferase
• Gene Name: B3GALNT1
• Related Disease:
  Brain neoplasm
  Diabetic kidney disease
  Non-small-cell lung cancer
  Neoplasm
  Pancreatic ductal carcinoma
• UniProt ID: B3GL1_HUMAN
• EC Number: 2.4.1.79
• Pfam ID: PF01762
• Sequence:
  MASALWTVLPSRMSLRSLKWSLLLLSLLSFFVMWYLSLPHYNVIERVNWMYFYEYEPIYR
  QDFHFTLREHSNCSHQNPFLVILVTSHPSDVKARQAIRVTWGEKKSWWGYEVLTFFLLGQ
  EAEKEDKMLALSLEDEHLLYGDIIRQDFLDTYNNLTLKTIMAFRWVTEFCPNAKYVMKTD
  TDVFINTGNLVKYLLNLNHSEKFFTGYPLIDNYSYRGFYQKTHISYQEYPFKVFPPYCSG
  LGYIMSRDLVPRIYEMMGHVKPIKFEDVYVGICLNLLKVNIHIPEDTNLFFLYRIHLDVC
  QLRRVIAAHGFSSKEIITFWQVMLRNTTCHY
• Function: Transfers N-acetylgalactosamine onto globotriaosylceramide. Plays a critical role in preimplantation stage embryonic development.
• Tissue Specificity: Higher expression in heart and brain, and to a lesser extent in lung, placenta, kidney and testis. Lower expression in liver, spleen and stomach. No expression in skeletal muscle.
• KEGG Pathway:
  Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)
  Glycosphingolipid biosynthesis - globo and isoglobo series (hsa00603)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Glycosphingolipid biosynthesis (R-HSA-9840309)
• BioCyc Pathway: MetaCyc:HS09918-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brain neoplasm	DISY3EKS	Strong	Biomarker	[1]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	moderate	Altered Expression	[4]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Altered Expression	[4]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1 (B3GALNT1).	[14]

References

• [1] UDP-Gal: betaGlcNAc beta1, 3-galactosyltransferase, polypeptide 3 (GALT3) is a tumour antigen recognised by HLA-A2-restricted cytotoxic T lymphocytes from patients with brain tumour.Br J Cancer. 2002 Oct 21;87(9):1006-12. doi: 10.1038/sj.bjc.6600593.
• [2] Globo-series glycosphingolipids enhance Toll-like receptor 4-mediated inflammation and play a pathophysiological role in diabetic nephropathy.Glycobiology. 2019 Mar 1;29(3):260-268. doi: 10.1093/glycob/cwy105.
• [3] TINAGL1 and B3GALNT1 are potential therapy target genes to suppress metastasis in non-small cell lung cancer.BMC Genomics. 2014;15 Suppl 9(Suppl 9):S2. doi: 10.1186/1471-2164-15-S9-S2. Epub 2014 Dec 8.
• [4] Shiga toxin glycosphingolipid receptor expression and toxin susceptibility of human pancreatic ductal adenocarcinomas of differing origin and differentiation.Biol Chem. 2012 Aug;393(8):785-99. doi: 10.1515/hsz-2012-0165.
• [5] 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.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] 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.
• [11] Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
• [12] 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.
• [13] 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.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.