Details of Drug Off-Target (DOT)

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

• DOT Name: Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B)
• Synonyms: EC 2.4.1.145; N-glycosyl-oligosaccharide-glycoprotein N-acetylglucosaminyltransferase IVb; GlcNAc-T IVb; GnT-IVb; N-acetylglucosaminyltransferase IVb; UDP-N-acetylglucosamine: alpha-1,3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase IVb
• Gene Name: MGAT4B
• Related Disease:
  Advanced cancer
  Choriocarcinoma
  Major depressive disorder
  Pancreatic tumour
• UniProt ID: MGT4B_HUMAN
• EC Number: 2.4.1.145
• Pfam ID: PF04666
• Sequence:
  MRLRNGTFLTLLLFCLCAFLSLSWYAALSGQKGDVVDVYQREFLALRDRLHAAEQESLKR
  SKELNLVLDEIKRAVSERQALRDGDGNRTWGRLTEDPRLKPWNGSHRHVLHLPTVFHHLP
  HLLAKESSLQPAVRVGQGRTGVSVVMGIPSVRREVHSYLTDTLHSLISELSPQEKEDSVI
  VVLIAETDSQYTSAVTENIKALFPTEIHSGLLEVISPSPHFYPDFSRLRESFGDPKERVR
  WRTKQNLDYCFLMMYAQSKGIYYVQLEDDIVAKPNYLSTMKNFALQQPSEDWMILEFSQL
  GFIGKMFKSLDLSLIVEFILMFYRDKPIDWLLDHILWVKVCNPEKDAKHCDRQKANLRIR
  FKPSLFQHVGTHSSLAGKIQKLKDKDFGKQALRKEHVNPPAEVSTSLKTYQHFTLEKAYL
  REDFFWAFTPAAGDFIRFRFFQPLRLERFFFRSGNIEHPEDKLFNTSVEVLPFDNPQSDK
  EALQEGRTATLRYPRSPDGYLQIGSFYKGVAEGEVDPAFGPLEALRLSIQTDSPVWVILS
  EIFLKKAD
• Function: Glycosyltransferase that catalyzes the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the production of tri- and tetra-antennary N-linked sugar chains. Prefers complex-type N-glycans over hybrid-types. Has lower affinities for donors or acceptors than MGAT4A, suggesting that, under physiological conditions, it is not the main contributor in N-glycan biosynthesis.
• Tissue Specificity: Widely expressed. Strongly overexpressed in pancreatic cancer.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Various types of N-glycan biosynthesis (hsa00513)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  N-Glycan antennae elongation (R-HSA-975577)
  Maturation of spike protein (R-HSA-9694548)
• BioCyc Pathway: MetaCyc:HS08564-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Choriocarcinoma	DISDBVNL	Strong	Altered Expression	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B) decreases the response to substance of Arsenic trioxide.	[13]

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 Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B).	[11]

6 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 Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B).	[10]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B (MGAT4B).	[12]

References

• [1] Unusually high expression of N-acetylglucosaminyltransferase-IVa in human choriocarcinoma cell lines: a possible enzymatic basis of the formation of abnormal biantennary sugar chain.Cancer Res. 1999 Aug 15;59(16):3949-53.
• [2] Identification of 15 genetic loci associated with risk of major depression in individuals of European descent.Nat Genet. 2016 Sep;48(9):1031-6. doi: 10.1038/ng.3623. Epub 2016 Aug 1.
• [3] Aberrant expression of N-acetylglucosaminyltransferase-IVa and IVb (GnT-IVa and b) in pancreatic cancer.Biochem Biophys Res Commun. 2006 Mar 10;341(2):478-82. doi: 10.1016/j.bbrc.2005.12.208. Epub 2006 Jan 11.
• [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] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [10] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [13] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.