Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1E09PZ)

• DOT Name: Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1)
• Synonyms: EC 2.4.1.101; N-glycosyl-oligosaccharide-glycoprotein N-acetylglucosaminyltransferase I; GNT-I; GlcNAc-T I
• Gene Name: MGAT1
• UniProt ID: MGAT1_HUMAN
• EC Number: 2.4.1.101
• Pfam ID: PF03071
• Sequence:
  MLKKQSAGLVLWGAILFVAWNALLLLFFWTRPAPGRPPSVSALDGDPASLTREVIRLAQD
  AEVELERQRGLLQQIGDALSSQRGRVPTAAPPAQPRVPVTPAPAVIPILVIACDRSTVRR
  CLDKLLHYRPSAELFPIIVSQDCGHEETAQAIASYGSAVTHIRQPDLSSIAVPPDHRKFQ
  GYYKIARHYRWALGQVFRQFRFPAAVVVEDDLEVAPDFFEYFRATYPLLKADPSLWCVSA
  WNDNGKEQMVDASRPELLYRTDFFPGLGWLLLAELWAELEPKWPKAFWDDWMRRPEQRQG
  RACIRPEISRTMTFGRKGVSHGQFFDQHLKFIKLNQQFVHFTQLDLSYLQREAYDRDFLA
  RVYGAPQLQVEKVRTNDRKELGEVRVQYTGRDSFKAFAKALGVMDDLKSGVPRAGYRGIV
  TFQFRGRRVHLAPPLTWEGYDPSWN
• Function: Initiates complex N-linked carbohydrate formation. Essential for the conversion of high-mannose to hybrid and complex N-glycans.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Various types of N-glycan biosynthesis (hsa00513)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Maturation of spike protein (R-HSA-9683686)
  Maturation of spike protein (R-HSA-9694548)
  N-glycan trimming and elongation in the cis-Golgi (R-HSA-964739)
• BioCyc Pathway: MetaCyc:HS05528-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1) increases the Metabolic disorder ADR of Chlorothiazide.	[9]

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 2-beta-N-acetylglucosaminyltransferase (MGAT1).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1).	[3]
Selenium	DM25CGV	Approved	Selenium increases the expression of Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1).	[4]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1).	[8]

References

• [1] 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.
• [2] 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.
• [3] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [4] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [5] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [6] 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.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] 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.
• [9] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.