Details of Drug Off-Target (DOT)

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

• DOT Name: Glucosidase 2 subunit beta (PRKCSH)
• Synonyms: 80K-H protein; Glucosidase II subunit beta; Protein kinase C substrate 60.1 kDa protein heavy chain; PKCSH
• Gene Name: PRKCSH
• Related Disease: Polycystic liver disease 1
• UniProt ID: GLU2B_HUMAN
• PDB ID: 8D43; 8EMR
• Pfam ID: PF13202 ; PF12999 ; PF13015
• Sequence:
  MLLPLLLLLPMCWAVEVKRPRGVSLTNHHFYDESKPFTCLDGSATIPFDQVNDDYCDCKD
  GSDEPGTAACPNGSFHCTNTGYKPLYIPSNRVNDGVCDCCDGTDEYNSGVICENTCKEKG
  RKERESLQQMAEVTREGFRLKKILIEDWKKAREEKQKKLIELQAGKKSLEDQVEMLRTVK
  EEAEKPEREAKEQHQKLWEEQLAAAKAQQEQELAADAFKELDDDMDGTVSVTELQTHPEL
  DTDGDGALSEAEAQALLSGDTQTDATSFYDRVWAAIRDKYRSEALPTDLPAPSAPDLTEP
  KEEQPPVPSSPTEEEEEEEEEEEEEAEEEEEEEDSEEAPPPLSPPQPASPAEEDKMPPYD
  EQTQAFIDAAQEARNKFEEAERSLKDMEESIRNLEQEISFDFGPNGEFAYLYSQCYELTT
  NEYVYRLCPFKLVSQKPKLGGSPTSLGTWGSWIGPDHDKFSAMKYEQGTGCWQGPNRSTT
  VRLLCGKETMVTSTTEPSRCEYLMELMTPAACPEPPPEAPTEDDHDEL
• Function: Regulatory subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins. Required for efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  N-glycan trimming in the ER and Calnexin/Calreticulin cycle (R-HSA-532668)
  Advanced glycosylation endproduct receptor signaling (R-HSA-879415)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Calnexin/calreticulin cycle (R-HSA-901042)
  Maturation of spike protein (R-HSA-9683686)
  Maturation of spike protein (R-HSA-9694548)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
• BioCyc Pathway: MetaCyc:HS05346-MONOMER

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 liver disease 1	DIS52T2A	Definitive	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glucosidase 2 subunit beta (PRKCSH).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Glucosidase 2 subunit beta (PRKCSH).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glucosidase 2 subunit beta (PRKCSH).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Glucosidase 2 subunit beta (PRKCSH).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Glucosidase 2 subunit beta (PRKCSH).	[6]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Glucosidase 2 subunit beta (PRKCSH).	[7]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Glucosidase 2 subunit beta (PRKCSH).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Glucosidase 2 subunit beta (PRKCSH).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Glucosidase 2 subunit beta (PRKCSH).	[9]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Glucosidase 2 subunit beta (PRKCSH).	[10]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [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] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [6] Analysis of gene expression induced by diethylstilbestrol (DES) in human primitive Mullerian duct cells using microarray. Cancer Lett. 2005 Apr 8;220(2):197-210.
• [7] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [8] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [9] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [10] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.