Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9PTWAX)

• DOT Name: Protein phosphatase 1 regulatory subunit 14B (PPP1R14B)
• Synonyms: Phospholipase C-beta-3 neighbouring gene protein
• Gene Name: PPP1R14B
• Related Disease:
  Human papillomavirus infection
  Melanoma
• UniProt ID: PP14B_HUMAN
• Pfam ID: PF05361
• Sequence:
  MADSGTAGGAALAAPAPGPGSGGPGPRVYFQSPPGAAGEGPGGADDEGPVRRQGKVTVKY
  DRKELRKRLNLEEWILEQLTRLYDCQEEEIPELEIDVDELLDMESDDARAARVKELLVDC
  YKPTEAFISGLLDKIRGMQKLSTPQKK
• Function: Inhibitor of PPP1CA. Has over 50-fold higher inhibitory activity when phosphorylated.
• Tissue Specificity: Ubiquitous. Expressed at low levels.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Human papillomavirus infection	DISX61LX	Limited	Biomarker	[1]
Melanoma	DIS1RRCY	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[8]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[7]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[15]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[16]

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 increases the methylation of Protein phosphatase 1 regulatory subunit 14B (PPP1R14B).	[11]

References

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• [2] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [10] A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
• [11] 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.
• [12] Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [16] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.