Details of Drug Off-Target (DOT)

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

• DOT Name: Phosphotriesterase-related protein (PTER)
• Synonyms: EC 3.1.-.-; Parathion hydrolase-related protein; hPHRP
• Gene Name: PTER
• Related Disease:
  Liver cancer
  Melanoma
  Obesity
  Tertiary syphilis
  Chronic renal failure
  End-stage renal disease
  Membranous glomerulonephritis
• UniProt ID: PTER_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF02126
• Sequence:
  MSSLSGKVQTVLGLVEPSKLGRTLTHEHLAMTFDCCYCPPPPCQEAISKEPIVMKNLYWI
  QKNAYSHKENLQLNQETEAIKEELLYFKANGGGALVENTTTGISRDTQTLKRLAEETGVH
  IISGAGFYVDATHSSETRAMSVEQLTDVLMNEILHGADGTSIKCGIIGEIGCSWPLTESE
  RKVLQATAHAQAQLGCPVIIHPGRSSRAPFQIIRILQEAGADISKTVMSHLDRTILDKKE
  LLEFAQLGCYLEYDLFGTELLHYQLGPDIDMPDDNKRIRRVRLLVEEGCEDRILVAHDIH
  TKTRLMKYGGHGYSHILTNVVPKMLLRGITENVLDKILIENPKQWLTFK

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Liver cancer	DISDE4BI	Strong	Biomarker	[1]
Melanoma	DIS1RRCY	Strong	Biomarker	[2]
Obesity	DIS47Y1K	Strong	Genetic Variation	[3]
Tertiary syphilis	DISXHT8N	Strong	Biomarker	[4]
Chronic renal failure	DISGG7K6	Limited	Biomarker	[5]
End-stage renal disease	DISXA7GG	Limited	Biomarker	[5]
Membranous glomerulonephritis	DISFSUKQ	Limited	Biomarker	[5]

12 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 Phosphotriesterase-related protein (PTER).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phosphotriesterase-related protein (PTER).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphotriesterase-related protein (PTER).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phosphotriesterase-related protein (PTER).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphotriesterase-related protein (PTER).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phosphotriesterase-related protein (PTER).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphotriesterase-related protein (PTER).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Phosphotriesterase-related protein (PTER).	[13]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Phosphotriesterase-related protein (PTER).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Phosphotriesterase-related protein (PTER).	[6]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Phosphotriesterase-related protein (PTER).	[18]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Phosphotriesterase-related protein (PTER).	[19]

3 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 Phosphotriesterase-related protein (PTER).	[15]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Phosphotriesterase-related protein (PTER).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Phosphotriesterase-related protein (PTER).	[17]

References

• [1] Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.PLoS One. 2014 Jul 24;9(7):e102579. doi: 10.1371/journal.pone.0102579. eCollection 2014.
• [2] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [3] Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples.Int J Obes (Lond). 2013 Feb;37(2):191-6. doi: 10.1038/ijo.2012.34. Epub 2012 Mar 20.
• [4] Incidence and Predictors of Serological Treatment Response in Early and Late Syphilis Among People Living With HIV.Open Forum Infect Dis. 2018 Nov 30;6(1):ofy324. doi: 10.1093/ofid/ofy324. eCollection 2019 Jan.
• [5] Phosphotriesterase-related protein sensed albuminuria and conferred renal tubular cell activation in membranous nephropathy.J Biomed Sci. 2014 Apr 22;21(1):32. doi: 10.1186/1423-0127-21-32.
• [6] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [7] 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.
• [8] 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.
• [9] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] 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.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [17] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [18] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [19] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.