Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM201HH)

• DOT Name: Fucose mutarotase (FUOM)
• Synonyms: EC 5.1.3.29
• Gene Name: FUOM
• UniProt ID: FUCM_HUMAN
• EC Number: 5.1.3.29
• Pfam ID: PF05025
• Sequence:
  MVALKGVPALLSPELLYALARMGHGDEIVLADLNFPASSICQCGPMEIRADGLGIPQLLE
  AVLKLLPLDTYVESPAAVMELVPSDKERGLQTPVWTEYESILRRAGCVRALAKIERFEFY
  ERAKKAFAVVATGETALYGNLILRKGVLALNPLL
• Function: Involved in the interconversion between alpha- and beta-L-fucoses. L-Fucose (6-deoxy-L-galactose) exists as alpha-L-fucose (29.5%) and beta-L-fucose (70.5%), the beta-form is metabolized through the salvage pathway. GDP-L-fucose formed either by the de novo or salvage pathways is transported into the endoplasmic reticulum, where it serves as a substrate for N- and O-glycosylations by fucosyltransferases. Fucosylated structures expressed on cell surfaces or secreted in biological fluids are believed to play a critical role in cell-cell adhesion and recognition processes.
• Reactome Pathway: GDP-fucose biosynthesis (R-HSA-6787639)

Molecular Interaction Atlas (MIA) of This DOT

9 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 Fucose mutarotase (FUOM).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fucose mutarotase (FUOM).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fucose mutarotase (FUOM).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fucose mutarotase (FUOM).	[4]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Fucose mutarotase (FUOM).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Fucose mutarotase (FUOM).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fucose mutarotase (FUOM).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Fucose mutarotase (FUOM).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Fucose mutarotase (FUOM).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Fucose mutarotase (FUOM).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fucose mutarotase (FUOM).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Fucose mutarotase (FUOM).	[10]

References

• [1] 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.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.