Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5G79NO)

• DOT Name: Protein O-glucosyltransferase 2 (POGLUT2)
• Synonyms: EC 2.4.1.-; Endoplasmic reticulum resident protein 58; ER protein 58; ERp58; KDEL motif-containing protein 1; Protein O-xylosyltransferase POGLUT2; EC 2.4.2.-
• Gene Name: POGLUT2
• Related Disease: Bipolar disorder
• UniProt ID: PLGT2_HUMAN
• PDB ID: 2DI7
• EC Number: 2.4.1.-; 2.4.2.-
• Pfam ID: PF00630 ; PF05686
• Sequence:
  MFGTLLLYCFFLATVPALAETGGERQLSPEKSEIWGPGLKADVVLPARYFYIQAVDTSGN
  KFTSSPGEKVFQVKVSAPEEQFTRVGVQVLDRKDGSFIVRYRMYASYKNLKVEIKFQGQH
  VAKSPYILKGPVYHENCDCPLQDSAAWLREMNCPETIAQIQRDLAHFPAVDPEKIAVEIP
  KRFGQRQSLCHYTLKDNKVYIKTHGEHVGFRIFMDAILLSLTRKVKMPDVELFVNLGDWP
  LEKKKSNSNIHPIFSWCGSTDSKDIVMPTYDLTDSVLETMGRVSLDMMSVQANTGPPWES
  KNSTAVWRGRDSRKERLELVKLSRKHPELIDAAFTNFFFFKHDENLYGPIVKHISFFDFF
  KHKYQINIDGTVAAYRLPYLLVGDSVVLKQDSIYYEHFYNELQPWKHYIPVKSNLSDLLE
  KLKWAKDHDEEAKKIAKAGQEFARNNLMGDDIFCYYFKLFQEYANLQVSEPQIREGMKRV
  EPQTEDDLFPCTCHRKKTKDEL
• Function: Protein glucosyltransferase that catalyzes the transfer of glucose from UDP-glucose to a serine residue within the consensus sequence peptide C-X-N-T-X-G-S-F-X-C. Can also catalyze the transfer of xylose from UDP-xylose but less efficiently. Specifically targets extracellular EGF repeats of proteins such as NOTCH1, NOTCH3, FBN1, FBN2 and LTBP1. May regulate the transport of NOTCH1 and NOTCH3 to the plasma membrane and thereby the Notch signaling pathway.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[11]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Protein O-glucosyltransferase 2 (POGLUT2).	[12]

References

• [1] Linkage disequilibrium analysis in the LOC93081-KDELC1-BIVM region on 13q in bipolar disorder.Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):12-7. doi: 10.1002/ajmg.b.30121.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.