Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZNC7R2)

• DOT Name: Protein phosphatase 1 regulatory subunit 3D (PPP1R3D)
• Synonyms: Protein phosphatase 1 regulatory subunit 6; PP1 subunit R6; Protein phosphatase 1-binding subunit R6
• Gene Name: PPP1R3D
• UniProt ID: PPR3D_HUMAN
• Pfam ID: PF03370
• Sequence:
  MSRGPSSAVLPSALGSRKLGPRSLSCLSDLDGGVALEPRACRPPGSPGRAPPPTPAPSGC
  DPRLRPIILRRARSLPSSPERRQKAAGAPGAACRPGCSQKLRVRFADALGLELAQVKVFN
  AGDDPSVPLHVLSRLAINSDLCCSSQDLEFTLHCLVPDFPPPVEAADFGERLQRQLVCLE
  RVTCSDLGISGTVRVCNVAFEKQVAVRYTFSGWRSTHEAVARWRGPAGPEGTEDVFTFGF
  PVPPFLLELGSRVHFAVRYQVAGAEYWDNNDHRDYSLTCRNHALHMPRGECEESWIHFI
• Function: Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis.
• Tissue Specificity: Expressed in all tissues tested. High expression in skeletal muscle and heart.
• KEGG Pathway:
  Insulin sig.ling pathway (hsa04910)
  Insulin resistance (hsa04931)

Molecular Interaction Atlas (MIA) of This DOT

11 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 Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein phosphatase 1 regulatory subunit 3D (PPP1R3D).	[10]

References

• [1] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 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.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [7] 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.
• [8] 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.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.