Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY5NVMJ)

• DOT Name: Plasma alpha-L-fucosidase (FUCA2)
• Synonyms: EC 3.2.1.51; Alpha-L-fucoside fucohydrolase 2; Alpha-L-fucosidase 2
• Gene Name: FUCA2
• Related Disease:
  Duodenal ulcer
  Autoimmune disease
  Fucosidosis
  Mucolipidosis
  Schizophrenia
  Sjogren syndrome
  Sickle-cell anaemia
• UniProt ID: FUCO2_HUMAN
• EC Number: 3.2.1.51
• Pfam ID: PF01120 ; PF16757
• Sequence:
  MRPQELPRLAFPLLLLLLLLLPPPPCPAHSATRFDPTWESLDARQLPAWFDQAKFGIFIH
  WGVFSVPSFGSEWFWWYWQKEKIPKYVEFMKDNYPPSFKYEDFGPLFTAKFFNANQWADI
  FQASGAKYIVLTSKHHEGFTLWGSEYSWNWNAIDEGPKRDIVKELEVAIRNRTDLRFGLY
  YSLFEWFHPLFLEDESSSFHKRQFPVSKTLPELYELVNNYQPEVLWSDGDGGAPDQYWNS
  TGFLAWLYNESPVRGTVVTNDRWGAGSICKHGGFYTCSDRYNPGHLLPHKWENCMTIDKL
  SWGYRREAGISDYLTIEELVKQLVETVSCGGNLLMNIGPTLDGTISVVFEERLRQMGSWL
  KVNGEAIYETHTWRSQNDTVTPDVWYTSKPKEKLVYAIFLKWPTSGQLFLGHPKAILGAT
  EVKLLGHGQPLNWISLEQNGIMVELPQLTIHQMPCKWGWALALTNVI
• Function: Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins.
• KEGG Pathway:
  Other glycan degradation (hsa00511)
  Lysosome (hsa04142)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Duodenal ulcer	DISNHHCN	Definitive	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[2]
Fucosidosis	DISCNE67	Strong	Biomarker	[3]
Mucolipidosis	DISOZ8DI	Strong	Biomarker	[4]
Schizophrenia	DISSRV2N	Strong	Biomarker	[5]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[6]
Sickle-cell anaemia	DIS5YNZB	Limited	Genetic Variation	[7]

6 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 Plasma alpha-L-fucosidase (FUCA2).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Plasma alpha-L-fucosidase (FUCA2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Plasma alpha-L-fucosidase (FUCA2).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Plasma alpha-L-fucosidase (FUCA2).	[11]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Plasma alpha-L-fucosidase (FUCA2).	[12]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Plasma alpha-L-fucosidase (FUCA2).	[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 decreases the methylation of Plasma alpha-L-fucosidase (FUCA2).	[13]

References

• [1] Role for alpha-L-fucosidase in the control of Helicobacter pylori-infected gastric cancer cells.Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14581-6. doi: 10.1073/pnas.0903286106. Epub 2009 Aug 7.
• [2] Plasma alpha-L-fucosidase activity in chronic inflammation and autoimmune disorders in a pediatric cohort of hospitalized patients.Immunol Res. 2017 Oct;65(5):1025-1030. doi: 10.1007/s12026-017-8943-x.
• [3] Development of Fluorogenic Substrates of -l-Fucosidase Useful for Inhibitor Screening and Gene-expression Profiling.ACS Med Chem Lett. 2019 Aug 26;10(9):1309-1313. doi: 10.1021/acsmedchemlett.9b00259. eCollection 2019 Sep 12.
• [4] Homozygosity for the variant alpha-L-fucosidase trait and mucolipidosis III.Hum Genet. 1985;70(1):71-3. doi: 10.1007/BF00389462.
• [5] Altered fucosyltransferase expression in the superior temporal gyrus of elderly patients with schizophrenia.Schizophr Res. 2017 Apr;182:66-73. doi: 10.1016/j.schres.2016.10.024. Epub 2016 Oct 20.
• [6] Plasma -L-fucosidase-1 in patients with Sjgren's syndrome and other rheumatic disorders.Int J Rheum Dis. 2019 Sep;22(9):1762-1767. doi: 10.1111/1756-185X.13639. Epub 2019 Aug 16.
• [7] Genome-Wide Analysis Identifies IL-18 and FUCA2 as Novel Genes Associated with Diastolic Function in African Americans with Sickle Cell Disease.PLoS One. 2016 Sep 16;11(9):e0163013. doi: 10.1371/journal.pone.0163013. eCollection 2016.
• [8] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [9] 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.
• [10] 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.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] 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.
• [13] 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.
• [14] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.