Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTODN616)

• DOT Name: Protein phosphatase 1 regulatory subunit 3E (PPP1R3E)
• Gene Name: PPP1R3E
• UniProt ID: PPR3E_HUMAN
• Pfam ID: PF03370
• Sequence:
  MSRERPPGTDIPRNLSFIAALTERAYYRSQRPSLEEEPEEEPGEGGTRFGARSRAHAPSR
  GRRARSAPAGGGGARAPRSRSPDTRKRVRFADALGLELAVVRRFRPGELPRVPRHVQIQL
  QRDALRHFAPCQPRARGLQEARAALEPASEPGFAARLLTQRICLERAEAGPLGVAGSARV
  VDLAYEKRVSVRWSADGWRSQREAPAAYAGPAPPPPRADRFAFRLPAPPIGGALLFALRY
  RVTGHEFWDNNGGRDYALRGPEHPGSGGAPEPQGWIHFI
• Function: Acts as a glycogen-targeting subunit for PP1. PP1 is involved in glycogen metabolism and contributes to the activation of glycogen synthase leading to an increase in glycogen synthesis.
• Tissue Specificity: Expressed in skeletal muscle and heart with barely detectable levels in liver.
• KEGG Pathway:
  Insulin sig.ling pathway (hsa04910)
  Insulin resistance (hsa04931)

Molecular Interaction Atlas (MIA) of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[4]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Protein phosphatase 1 regulatory subunit 3E (PPP1R3E).	[13]

References

• [1] 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.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] 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.
• [5] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] 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.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] Gene expression profiling analysis of bisphenol A-induced perturbation in biological processes in ER-negative HEK293 cells. PLoS One. 2014 Jun 5;9(6):e98635.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.