Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8UTTXF)

• DOT Name: UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7)
• Synonyms: BGnT-7; Beta-1,3-Gn-T7; Beta-1,3-N-acetylglucosaminyltransferase 7; Beta3Gn-T7; EC 2.4.1.-
• Gene Name: B3GNT7
• Related Disease:
  Colon adenocarcinoma
  Colon cancer
  Colon carcinoma
• UniProt ID: B3GN7_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF01762
• Sequence:
  MSLWKKTVYRSLCLALALLVAVTVFQRSLTPGQFLQEPPPPTLEPQKAQKPNGQLVNPNN
  FWKNPKDVAAPTPMASQGPQAWDVTTTNCSANINLTHQPWFQVLEPQFRQFLFYRHCRYF
  PMLLNHPEKCRGDVYLLVVVKSVITQHDRREAIRQTWGRERQSAGGGRGAVRTLFLLGTA
  SKQEERTHYQQLLAYEDRLYGDILQWGFLDTFFNLTLKEIHFLKWLDIYCPHVPFIFKGD
  DDVFVNPTNLLEFLADRQPQENLFVGDVLQHARPIRRKDNKYYIPGALYGKASYPPYAGG
  GGFLMAGSLARRLHHACDTLELYPIDDVFLGMCLEVLGVQPTAHEGFKTFGISRNRNSRM
  NKEPCFFRAMLVVHKLLPPELLAMWGLVHSNLTCSRKLQVL
• Function: N-acetyl glucosamine (GlcNAc) transferase that catalyzes the transfer of GlcNAc via a beta1->3 linkage from UDP-GlcNAc to the non-reducing terminal galactose (Gal) in the linearly growing chain of N- and O-linked keratan sulfate proteoglycans. Cooperates with B4GALT4 galactosyltransferase and CHST6 and CHST1 sulfotransferases to construct and elongate mono- and disulfated disaccharide units [->3Galbeta1->4(6-sulfoGlcNAcbeta)1->] and [->3(6-sulfoGalbeta)1->4(6-sulfoGlcNAcbeta)1->] within keratan sulfate polymer. Involved in biosynthesis of N-linked keratan sulfate proteoglycans in cornea, with an impact on proteoglycan fibril organization and corneal transparency. May play a role in the maintenance of tissue architecture by suppressing cellular motility and invasion.
• Tissue Specificity: Expressed in corneal epithelial cells.
• KEGG Pathway: Glycosaminoglycan biosynthesis - keratan sulfate (hsa00533)
• Reactome Pathway:
  O-linked glycosylation of mucins (R-HSA-913709)
  Keratan sulfate biosynthesis (R-HSA-2022854)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon adenocarcinoma	DISDRE0J	Limited	Altered Expression	[1]
Colon cancer	DISVC52G	Limited	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Limited	Genetic Variation	[1]

3 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 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7).	[11]

References

• [1] Suppression of B3GNT7 gene expression in colon adenocarcinoma and its potential effect in the metastasis of colon cancer cells.Glycobiology. 2014 Apr;24(4):359-67. doi: 10.1093/glycob/cwu002. Epub 2014 Jan 12.
• [2] 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.
• [3] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] 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.
• [11] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.