Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAX8BNJ)

• DOT Name: Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase (B3GNT6)
• Synonyms: EC 2.4.1.147; Core 3 synthase; UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6; BGnT-6; Beta-1,3-Gn-T6; Beta-1,3-N-acetylglucosaminyltransferase 6; Beta3Gn-T6
• Gene Name: B3GNT6
• Related Disease:
  Advanced cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Familial adenomatous polyposis
  Neoplasm
  Pancreatic cancer
  Pancreatic tumour
• UniProt ID: B3GN6_HUMAN
• EC Number: 2.4.1.147
• Pfam ID: PF01762
• Sequence:
  MAFPCRRSLTAKTLACLLVGVSFLALQQWFLQAPRSPREERSPQEETPEGPTDAPAADEP
  PSELVPGPPCVANASANATADFEQLPARIQDFLRYRHCRHFPLLWDAPAKCAGGRGVFLL
  LAVKSAPEHYERRELIRRTWGQERSYGGRPVRRLFLLGTPGPEDEARAERLAELVALEAR
  EHGDVLQWAFADTFLNLTLKHLHLLDWLAARCPHARFLLSGDDDVFVHTANVVRFLQAQP
  PGRHLFSGQLMEGSVPIRDSWSKYFVPPQLFPGSAYPVYCSGGGFLLSGPTARALRAAAR
  HTPLFPIDDAYMGMCLERAGLAPSGHEGIRPFGVQLPGAQQSSFDPCMYRELLLVHRFAP
  YEMLLMWKALHSPALSCDRGHRVS
• Function: Beta-1,3-N-acetylglucosaminyltransferase that synthesizes the core 3 structure of the O-glycan, an important precursor in the biosynthesis of mucin-type glycoproteins. Plays an important role in the synthesis of mucin-type O-glycans in digestive organs.
• Tissue Specificity: Present in stomach and colon (at protein level). Restricted in the stomach, colon and small intestine, where core 3 structure is present.
• KEGG Pathway:
  Mucin type O-glycan biosynthesis (hsa00512)
  Metabolic pathways (hsa01100)
• Reactome Pathway: O-linked glycosylation of mucins (R-HSA-913709)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[2]
Familial adenomatous polyposis	DISW53RE	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[1]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[1]

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 Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase (B3GNT6).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase (B3GNT6).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase (B3GNT6).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase (B3GNT6).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase (B3GNT6).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase (B3GNT6).	[8]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase (B3GNT6).	[9]

References

• [1] Expression of core 3 synthase in human pancreatic cancer cells suppresses tumor growth and metastasis.Int J Cancer. 2013 Dec 15;133(12):2824-33. doi: 10.1002/ijc.28322. Epub 2013 Aug 5.
• [2] Core 3 synthase is down-regulated in colon carcinoma and profoundly suppresses the metastatic potential of carcinoma cells.Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4572-7. doi: 10.1073/pnas.0407983102. Epub 2005 Mar 8.
• [3] Core 3 mucin-type O-glycan restoration in colorectal cancer cells promotes MUC1/p53/miR-200c-dependent epithelial identity.Oncogene. 2017 Nov 16;36(46):6391-6407. doi: 10.1038/onc.2017.241. Epub 2017 Jul 24.
• [4] 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.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] 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.
• [7] 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.
• [8] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [9] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [10] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.