Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT006CEI)

• DOT Name: Dolichyl-phosphate beta-glucosyltransferase (ALG5)
• Synonyms: DolP-glucosyltransferase; EC 2.4.1.117; Asparagine-linked glycosylation protein 5 homolog
• Gene Name: ALG5
• Related Disease: Polycystic kidney disease 7
• UniProt ID: ALG5_HUMAN
• EC Number: 2.4.1.117
• Pfam ID: PF00535
• Sequence:
  MAPLLLQLAVLGAALAAAALVLISIVAFTTATKMPALHRHEEEKFFLNAKGQKETLPSIW
  DSPTKQLSVVVPSYNEEKRLPVMMDEALSYLEKRQKRDPAFTYEVIVVDDGSKDQTSKVA
  FKYCQKYGSDKVRVITLVKNRGKGGAIRMGIFSSRGEKILMADADGATKFPDVEKLEKGL
  NDLQPWPNQMAIACGSRAHLEKESIAQRSYFRTLLMYGFHFLVWFLCVKGIRDTQCGFKL
  FTREAASRTFSSLHVERWAFDVELLYIAQFFKIPIAEIAVNWTEIEGSKLVPFWSWLQMG
  KDLLFIRLRYLTGAWRLEQTRKMN
• Function: Required for the assembly of lipid-linked oligosaccharides in kidney epithelial cells, and protein N-glycosylation. Required for polycystin-1 (PKD1) glycosylation and maturation.
• Tissue Specificity: Expressed in pancreas, placenta, liver, heart, brain, kidney, skeletal muscle, and lung.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of dolichyl-phosphate-glucose (R-HSA-480985)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Polycystic kidney disease 7	DISIYFO0	Strong	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dolichyl-phosphate beta-glucosyltransferase (ALG5).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dolichyl-phosphate beta-glucosyltransferase (ALG5).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dolichyl-phosphate beta-glucosyltransferase (ALG5).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Dolichyl-phosphate beta-glucosyltransferase (ALG5).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Dolichyl-phosphate beta-glucosyltransferase (ALG5).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Dolichyl-phosphate beta-glucosyltransferase (ALG5).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Dolichyl-phosphate beta-glucosyltransferase (ALG5).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Dolichyl-phosphate beta-glucosyltransferase (ALG5).	[9]

References

• [1] Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis. Am J Hum Genet. 2022 Aug 4;109(8):1484-1499. doi: 10.1016/j.ajhg.2022.06.013. Epub 2022 Jul 26.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] 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.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] 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.
• [8] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [9] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.