Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT19635T)

• DOT Name: Protein phosphatase 1 regulatory subunit 17 (PPP1R17)
• Synonyms: G-substrate
• Gene Name: PPP1R17
• Related Disease:
  Lung adenocarcinoma
  Parkinson disease
• UniProt ID: PPR17_HUMAN
• Sequence:
  MMSTEQMQPLELSEDRLDKLDPRCSHLDDLSDQFIKDCDLKKKPRKGKNVQATLNVESDQ
  KKPRRKDTPALHIPPFIPGVFSEHLIKRYDVQERHPKGKMIPVLHNTDLEQKKPRRKDTP
  ALHMSPFAAGVTLLRDERPKAIVEDDEKDGDKIAI
• Function: Inhibits phosphatase activities of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) complexes.
• Tissue Specificity: Highly expressed in cerebellum.
• KEGG Pathway: Long-term depression (hsa04730)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[1]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[2]

8 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 phosphatase 1 regulatory subunit 17 (PPP1R17).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein phosphatase 1 regulatory subunit 17 (PPP1R17).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein phosphatase 1 regulatory subunit 17 (PPP1R17).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein phosphatase 1 regulatory subunit 17 (PPP1R17).	[6]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Protein phosphatase 1 regulatory subunit 17 (PPP1R17).	[5]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Protein phosphatase 1 regulatory subunit 17 (PPP1R17).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein phosphatase 1 regulatory subunit 17 (PPP1R17).	[9]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Protein phosphatase 1 regulatory subunit 17 (PPP1R17).	[10]

1 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 Protein phosphatase 1 regulatory subunit 17 (PPP1R17).	[8]

References

• [1] Identification of stage-specific biomarkers in lung adenocarcinoma based on RNA-seq data.Tumour Biol. 2015 Aug;36(8):6391-9. doi: 10.1007/s13277-015-3327-0. Epub 2015 Apr 11.
• [2] An endogenous serine/threonine protein phosphatase inhibitor, G-substrate, reduces vulnerability in models of Parkinson's disease.J Neurosci. 2007 Aug 1;27(31):8314-23. doi: 10.1523/JNEUROSCI.1972-07.2007.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on cervical carcinoma cells. Int J Gynecol Cancer. 2006 May-Jun;16(3):1321-9.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] 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.
• [9] 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.
• [10] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.