Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUX45ZF)

• DOT Name: Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG)
• Synonyms: EC 2.4.1.222; O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase
• Gene Name: MFNG
• UniProt ID: MFNG_HUMAN
• EC Number: 2.4.1.222
• Pfam ID: PF02434
• Sequence:
  MQCRLPRGLAGALLTLLCMGLLCLRYHLNLSPQRVQGTPELSQPNPGPPKLQLHDVFIAV
  KTTRAFHRLRLELLLDTWVSRTREQTFVFTDSPDKGLQERLGSHLVVTNCSAEHSHPALS
  CKMAAEFDTFLASGLRWFCHVDDDNYVNPRALLQLLRAFPLARDVYVGRPSLNRPIHASE
  PQPHNRTRLVQFWFATGGAGFCINRKLALKMAPWASGSRFMDTSALIRLPDDCTMGYIIE
  CKLGGRLQPSPLFHSHLETLQLLRTAQLPEQVTLSYGVFEGKLNVIKLQGPFSPEEDPSR
  FRSLHCLLYPDTPWCPQLGAR
• Function: Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. Modulates NOTCH1 activity by modifying O-fucose residues at specific EGF-like domains resulting in inhibition of NOTCH1 activation by JAG1 and enhancement of NOTCH1 activation by DLL1 via an increase in its binding to DLL1.
• KEGG Pathway:
  Other types of O-glycan biosynthesis (hsa00514)
  Notch sig.ling pathway (hsa04330)
  Human papillomavirus infection (hsa05165)
• Reactome Pathway: Pre-NOTCH Processing in Golgi (R-HSA-1912420)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[9]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[5]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[14]

1 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 Beta-1,3-N-acetylglucosaminyltransferase manic fringe (MFNG).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] 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.
• [7] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [11] 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.
• [12] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.