Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6BFB22)

• DOT Name: Beta-1,4-N-acetylgalactosaminyltransferase 3 (B4GALNT3)
• Synonyms: B4GalNAcT3; Beta4GalNAc-T3; Beta4GalNAcT3; EC 2.4.1.244; Beta-1,4-N-acetylgalactosaminyltransferase III; N-acetyl-beta-glucosaminyl-glycoprotein 4-beta-N-acetylgalactosaminyltransferase 2; NGalNAc-T2
• Gene Name: B4GALNT3
• Related Disease:
  Ovarian cancer
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Osteoarthritis
  Thyroid gland papillary carcinoma
• UniProt ID: B4GN3_HUMAN
• EC Number: 2.4.1.244
• Pfam ID: PF05679 ; PF07691
• Sequence:
  MGSPRAARPPLLLRPVKLLRRRFRLLLALAVVSVGLWTLYLELVASAQVGGNPLNRRYGS
  WRELAKALASRNIPAVDPHLQFYHPQRLSLEDHDIDQGVSSNSSYLKWNKPVPWLSEFRG
  RANLHVFEDWCGSSIQQLRRNLHFPLYPHIRTTLRKLAVSPKWTNYGLRIFGYLHPFTDG
  KIQFAIAADDNAEFWLSLDDQVSGLQLLASVGKTGKEWTAPGEFGKFRSQISKPVSLSAS
  HRYYFEVLHKQNEEGTDHVEVAWRRNDPGAKFTIIDSLSLSLFTNETFLQMDEVGHIPQT
  AASHVDSSNALPRDEQPPADMLRPDPRDTLYRVPLIPKSHLRHVLPDCPYKPSYLVDGLP
  LQRYQGLRFVHLSFVYPNDYTRLSHMETHNKCFYQENAYYQDRFSFQEYIKIDQPEKQGL
  EQPGFEENLLEESQYGEVAEETPASNNQNARMLEGRQTPASTLEQDATDYRLRSLRKLLA
  QPREGLLAPFSKRNSTASFPGRTSHIPVQQPEKRKQKPSPEPSQDSPHSDKWPPGHPVKN
  LPQMRGPRPRPAGDSPRKTQWLNQVESYIAEQRRGDRMRPQAPGRGWHGEEEVVAAAGQE
  GQVEGEEEGEEEEEEEDMSEVFEYVPVFDPVVNWDQTFSARNLDFQALRTDWIDLSCNTS
  GNLLLPEQEALEVTRVFLKKLNQRSRGRYQLQRIVNVEKRQDQLRGGRYLLELELLEQGQ
  RVVRLSEYVSARGWQGIDPAGGEEVEARNLQGLVWDPHNRRRQVLNTRAQEPKLCWPQGF
  SWSHRAVVHFVVPVKNQARWVQQFIKDMENLFQVTGDPHFNIVITDYSSEDMDVEMALKR
  SKLRSYQYVKLSGNFERSAGLQAGIDLVKDPHSIIFLCDLHIHFPAGVIDAIRKHCVEGK
  MAFAPMVMRLHCGATPQWPEGYWEVNGFGLLGIYKSDLDRIGGMNTKEFRDRWGGEDWEL
  LDRILQAGLDVERLSLRNFFHHFHSKRGMWSRRQMKTL
• Function: Transfers N-acetylgalactosamine (GalNAc) from UDP-GalNAc to N-acetylglucosamine-beta-benzyl with a beta-1,4-linkage to form N,N'-diacetyllactosediamine, GalNAc-beta-1,4-GlcNAc structures in N-linked glycans and probably O-linked glycans. Mediates the N,N'-diacetyllactosediamine formation on gastric mucosa.
• Tissue Specificity: Highly expressed in testis, colon and stomach. Weakly expressed in other tissues.
• KEGG Pathway:
  Various types of N-glycan biosynthesis (hsa00513)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ovarian cancer	DISZJHAP	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[3]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Beta-1,4-N-acetylgalactosaminyltransferase 3 (B4GALNT3).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Beta-1,4-N-acetylgalactosaminyltransferase 3 (B4GALNT3).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Beta-1,4-N-acetylgalactosaminyltransferase 3 (B4GALNT3).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Beta-1,4-N-acetylgalactosaminyltransferase 3 (B4GALNT3).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Beta-1,4-N-acetylgalactosaminyltransferase 3 (B4GALNT3).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Beta-1,4-N-acetylgalactosaminyltransferase 3 (B4GALNT3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Beta-1,4-N-acetylgalactosaminyltransferase 3 (B4GALNT3).	[7]

References

• [1] Tissue glycomics distinguish tumour sites in women with advanced serous adenocarcinoma.Mol Oncol. 2017 Nov;11(11):1595-1615. doi: 10.1002/1878-0261.12134. Epub 2017 Sep 29.
• [2] 1, 4-N-acetylgalactosaminyltransferase III modulates cancer stemness through EGFR signaling pathway in colon cancer cells.Oncotarget. 2014 Jun 15;5(11):3673-84. doi: 10.18632/oncotarget.1981.
• [3] Glycophenotyping of osteoarthritic cartilage and chondrocytes by RT-qPCR, mass spectrometry, histochemistry with plant/human lectins and lectin localization with a glycoprotein.Arthritis Res Ther. 2013 Oct 4;15(5):R147. doi: 10.1186/ar4330.
• [4] New somatic mutations and WNK1-B4GALNT3 gene fusion in papillary thyroid carcinoma.Oncotarget. 2015 May 10;6(13):11242-51. doi: 10.18632/oncotarget.3593.
• [5] 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.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.