Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKXMSM7)

• DOT Name: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2)
• Synonyms: EC 2.4.1.143; Beta-1,2-N-acetylglucosaminyltransferase II; GlcNAc-T II; GNT-II; Mannoside acetylglucosaminyltransferase 2; N-glycosyl-oligosaccharide-glycoprotein N-acetylglucosaminyltransferase II
• Gene Name: MGAT2
• Related Disease: MGAT2-congenital disorder of glycosylation
• UniProt ID: MGAT2_HUMAN
• PDB ID: 5VCM; 5VCR; 5VCS
• EC Number: 2.4.1.143
• Pfam ID: PF05060
• Sequence:
  MRFRIYKRKVLILTLVVAACGFVLWSSNGRQRKNEALAPPLLDAEPARGAGGRGGDHPSV
  AVGIRRVSNVSAASLVPAVPQPEADNLTLRYRSLVYQLNFDQTLRNVDKAGTWAPRELVL
  VVQVHNRPEYLRLLLDSLRKAQGIDNVLVIFSHDFWSTEINQLIAGVNFCPVLQVFFPFS
  IQLYPNEFPGSDPRDCPRDLPKNAALKLGCINAEYPDSFGHYREAKFSQTKHHWWWKLHF
  VWERVKILRDYAGLILFLEEDHYLAPDFYHVFKKMWKLKQQECPECDVLSLGTYSASRSF
  YGMADKVDVKTWKSTEHNMGLALTRNAYQKLIECTDTFCTYDDYNWDWTLQYLTVSCLPK
  FWKVLVPQIPRIFHAGDCGMHHKKTCRPSTQSAQIESLLNNNKQYMFPETLTISEKFTVV
  AISPPRKNGGWGDIRDHELCKSYRRLQ
• Function: Plays an essential role in protein N-glycosylation. Catalyzes the transfer of N-acetylglucosamine (GlcNAc) onto the free terminal mannose moiety in the core structure of the nascent N-linked glycan chain, giving rise to the second branch in complex 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-9694548)
  Reactions specific to the complex N-glycan synthesis pathway (R-HSA-975578)
  Defective MGAT2 causes CDG-2a (R-HSA-4793952)
• BioCyc Pathway: MetaCyc:HS09725-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
MGAT2-congenital disorder of glycosylation	DISVNSO7	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2) affects the response to substance of Fluorouracil.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2).	[4]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2).	[5]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2).	[7]
Phenol	DM1QSM3	Phase 2/3	Phenol decreases the expression of Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2).	[9]

References

• [1] Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain development. Am J Hum Genet. 1996 Oct;59(4):810-7.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [6] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [10] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.