Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOA7YX7)

• DOT Name: Protein phosphatase 1 regulatory subunit 16A (PPP1R16A)
• Synonyms: Myosin phosphatase-targeting subunit 3
• Gene Name: PPP1R16A
• UniProt ID: PP16A_HUMAN
• Pfam ID: PF12796
• Sequence:
  MAEHLELLAEMPMVGRMSTQERLKHAQKRRAQQVKMWAQAEKEAQGKKGPGERPRKEAAS
  QGLLKQVLFPPSVVLLEAAARNDLEEVRQFLGSGVSPDLANEDGLTALHQCCIDDFREMV
  QQLLEAGANINACDSECWTPLHAAATCGHLHLVELLIASGANLLAVNTDGNMPYDLCDDE
  QTLDCLETAMADRGITQDSIEAARAVPELRMLDDIRSRLQAGADLHAPLDHGATLLHVAA
  ANGFSEAAALLLEHRASLSAKDQDGWEPLHAAAYWGQVPLVELLVAHGADLNAKSLMDET
  PLDVCGDEEVRAKLLELKHKHDALLRAQSRQRSLLRRRTSSAGSRGKVVRRVSLTQRTDL
  YRKQHAQEAIVWQQPPPTSPEPPEDNDDRQTGAELRPPPPEEDNPEVVRPHNGRVGGSPV
  RHLYSKRLDRSVSYQLSPLDSTTPHTLVHDKAHHTLADLKRQRAAAKLQRPPPEGPESPE
  TAEPGLPGDTVTPQPDCGFRAGGDPPLLKLTAPAVEAPVERRPCCLLM
• Function: Inhibits protein phosphatase 1 activity toward phosphorylase, myosin light chain and myosin substrates.

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 16A (PPP1R16A).	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein phosphatase 1 regulatory subunit 16A (PPP1R16A).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein phosphatase 1 regulatory subunit 16A (PPP1R16A).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein phosphatase 1 regulatory subunit 16A (PPP1R16A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein phosphatase 1 regulatory subunit 16A (PPP1R16A).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein phosphatase 1 regulatory subunit 16A (PPP1R16A).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein phosphatase 1 regulatory subunit 16A (PPP1R16A).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein phosphatase 1 regulatory subunit 16A (PPP1R16A).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein phosphatase 1 regulatory subunit 16A (PPP1R16A).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein phosphatase 1 regulatory subunit 16A (PPP1R16A).	[2]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Protein phosphatase 1 regulatory subunit 16A (PPP1R16A).	[7]

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] 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.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [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.