Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ2R629)

• DOT Name: Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C (MGAT4C)
• Synonyms: EC 2.4.1.145; N-acetylglucosaminyltransferase IV homolog; hGnT-IV-H; N-glycosyl-oligosaccharide-glycoprotein N-acetylglucosaminyltransferase IVc; GlcNAc-T IVc; GnT-IVc; N-acetylglucosaminyltransferase IVc; UDP-N-acetylglucosamine: alpha-1,3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase IVc
• Gene Name: MGAT4C
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Chronic renal failure
  End-stage renal disease
  Non-insulin dependent diabetes
• UniProt ID: MGT4C_HUMAN
• EC Number: 2.4.1.145
• Pfam ID: PF04666
• Sequence:
  MFKFHQMKHIFEILDKMRCLRKRSTVSFLGVLVIFLLFMNLYIEDSYVLEGDKQLIRETS
  THQLNSERYVHTFKDLSNFSGAINVTYRYLAATPLQRKRYLTIGLSSVKRKKGNYLLETI
  KSIFEQSSYEELKEISVVVHLADFNSSWRDAMVQDITQKFAHHIIAGRLMVIHAPEEYYP
  ILDGLKRNYNDPEDRVKFRSKQNVDYAFLLNFCANTSDYYVMLEDDVRCSKNFLTAIKKV
  IASLEGTYWVTLEFSKLGYIGKLYHSHDLPRLAHFLLMFYQEMPCDWLLTHFRGLLAQKN
  VIRFKPSLFQHMGYYSSYKGTENKLKDDDFEEESFDIPDNPPASLYTNMNVFENYEASKA
  YSSVDEYFWGKPPSTGDVFVIVFENPIIIKKIKVNTGTEDRQNDILHHGALDVGENVMPS
  KQRRQCSTYLRLGEFKNGNFEMSGVNQKIPFDIHCMRIYVTKTQKEWLIIRSISIWTS
• Function: Glycosyltransferase that participates in the transfer of N-acetylglucosamine (GlcNAc) to the core mannose residues of N-linked glycans. Catalyzes the formation of the GlcNAcbeta1-4 branch on the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans. Essential for the production of tri- and tetra-antennary N-linked sugar chains. Does not catalyze the transfer of GlcNAc to the Manalpha1-6 arm to form GlcNAcBeta1-4Manalpha1-6 linkage ('GnT-VI' activity).
• Tissue Specificity: Expressed in heart, adrenal gland, testis, liver, brain and fetal brain. Not expressed in pancreas.
• 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:HS00017-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	moderate	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[1]
Chronic renal failure	DISGG7K6	Limited	Genetic Variation	[2]
End-stage renal disease	DISXA7GG	Limited	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[2]

7 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 C (MGAT4C).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C (MGAT4C).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C (MGAT4C).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C (MGAT4C).	[4]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C (MGAT4C).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C (MGAT4C).	[8]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C (MGAT4C).	[6]

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 decreases the methylation of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C (MGAT4C).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C (MGAT4C).	[9]

References

• [1] Identification of functionally active, low frequency copy number variants at 15q21.3 and 12q21.31 associated with prostate cancer risk.Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6686-91. doi: 10.1073/pnas.1117405109. Epub 2012 Apr 10.
• [2] Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans.Hum Genomics. 2019 May 15;13(1):21. doi: 10.1186/s40246-019-0205-7.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [7] 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.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] 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.