Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBTJI73)

• DOT Name: Protein O-glucosyltransferase 3 (POGLUT3)
• Synonyms: EC 2.4.1.-; KDEL motif-containing protein 2; Protein O-xylosyltransferase POGLUT3; EC 2.4.2.-
• Gene Name: POGLUT3
• Related Disease:
  Breast carcinoma
  Renal cell carcinoma
  Uterine fibroids
• UniProt ID: PLGT3_HUMAN
• EC Number: 2.4.1.-; 2.4.2.-
• Pfam ID: PF00630 ; PF05686
• Sequence:
  MRRLPRALLLQLRLALLVAAGAPEVLVSAPRSLVWGPGLQAAVVLPVRYFYLQAVNSEGQ
  NLTRSPAGETPFKVVVKSLSPKELVRIHVPKPLDRNDGTFLMRYRMYETVDEGLKIEVLY
  GDEHVAQSPYILKGPVYHEYCECPEDPQAWQKTLSCPTKEPQIAKDFASFPSINLQQMLK
  EVPKRFGDERGAIVHYTILNNHVYRRSLGKYTDFKMFSDEILLSLTRKVLLPDLEFYVNL
  GDWPLEHRKVNGTPSPIPIISWCGSLDSRDVVLPTYDITHSMLEAMRGVTNDLLSIQGNT
  GPSWINKTERAFFRGRDSREERLQLVQLSKENPQLLDAGITGYFFFQEKEKELGKAKLMG
  FFDFFKYKYQVNVDGTVAAYRYPYLMLGDSLVLKQDSPYYEHFYMALEPWKHYVPIKRNL
  SDLLEKVKWAKENDEEAKKIAKEGQLMARDLLQPHRLYCYYYQVLQKYAERQSSKPEVRD
  GMELVPQPEDSTAICQCHRKKPSREEL
• 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

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[2]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[3]

12 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 Protein O-glucosyltransferase 3 (POGLUT3).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[10]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein O-glucosyltransferase 3 (POGLUT3).	[15]

References

• [1] Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.Nat Genet. 2017 Dec;49(12):1767-1778. doi: 10.1038/ng.3785. Epub 2017 Oct 23.
• [2] Genome-wide association study identifies multiple risk loci for renal cell carcinoma.Nat Commun. 2017 Jun 9;8:15724. doi: 10.1038/ncomms15724.
• [3] Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.Nat Commun. 2019 Oct 24;10(1):4857. doi: 10.1038/s41467-019-12536-4.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] 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.
• [10] Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells. Environ Toxicol. 2018 Nov;33(11):1168-1181. doi: 10.1002/tox.22623. Epub 2018 Aug 27.
• [11] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] 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.
• [15] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.