Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFXJK3V)

• DOT Name: Protein phosphatase 1 regulatory subunit 3G (PPP1R3G)
• Gene Name: PPP1R3G
• Related Disease:
  Fatty liver disease
  Obesity
• UniProt ID: PP13G_HUMAN
• Pfam ID: PF03370
• Sequence:
  MEPIGARLSLEAPGPAPFREAPPAEELPAPVVPCVQGGGDGGGASETPSPDAQLGDRPLS
  PKEEAAPQEQEELLECRRRCRARSFSLPADPILQAAKFLQQQQQQAVALGGEGAEDAQLG
  PGGCCAKCKKRVQFADTLGLSLASVKHFSEAEEPQVPPAVLSRLRSFPMRAEDLEQLGGL
  LAAAAVAAPLSAPPSRLRPLFQLPGPSAAAERLQRQRVCLERVQCSTASGAEVKGSGRVL
  SCPGPRAVTVRYTFTEWRSFLDVPAELQPEPLEPQQPEAPSGASEPGSGDAKKEPGAECF
  HFSLCLPPGLQPEDEEDADERGVAVHFAVCYRCAQGEYWDNNAGANYTLRYARPADAL
• Function: Glycogen-targeting subunit for protein phosphatase 1 (PP1). Involved in the regulation of hepatic glycogenesis in a manner coupled to the fasting-feeding cycle and distinct from other glycogen-targeting subunits.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fatty liver disease	DIS485QZ	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[1]

4 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 3G (PPP1R3G).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein phosphatase 1 regulatory subunit 3G (PPP1R3G).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein phosphatase 1 regulatory subunit 3G (PPP1R3G).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein phosphatase 1 regulatory subunit 3G (PPP1R3G).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein phosphatase 1 regulatory subunit 3G (PPP1R3G).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein phosphatase 1 regulatory subunit 3G (PPP1R3G).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein phosphatase 1 regulatory subunit 3G (PPP1R3G).	[8]

References

• [1] Ablation of PPP1R3G reduces glycogen deposition and mitigates high-fat diet induced obesity.Mol Cell Endocrinol. 2017 Jan 5;439:133-140. doi: 10.1016/j.mce.2016.10.036. Epub 2016 Nov 2.
• [2] 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.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.