Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXRH3YA)

DOT Name Protein phosphatase 1E (PPM1E)
Synonyms EC 3.1.3.16; Ca(2+)/calmodulin-dependent protein kinase phosphatase N; CaMKP-N; CaMKP-nucleus; CaMKN; Partner of PIX 1; Partner of PIX-alpha; Partner of PIXA
Gene Name PPM1E
Related Disease
Colorectal carcinoma ( )
Advanced cancer ( )
Breast cancer ( )
Testicular germ cell tumor ( )
Breast carcinoma ( )
Gastric cancer ( )
Stomach cancer ( )
Colorectal neoplasm ( )
UniProt ID
PPM1E_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.1.3.16
Pfam ID
PF00481
Sequence
MAGCIPEEKTYRRFLELFLGEFRGPCGGGEPEPEPEPEPEPEPESEPEPEPELVEAEAAE
ASVEEPGEEAATVAATEEGDQEQDPEPEEEAAVEGEEEEEGAATAAAAPGHSAVPPPPPQ
LPPLPPLPRPLSERITREEVEGESLDLCLQQLYKYNCPSFLAAALARATSDEVLQSDLSA
HYIPKETDGTEGTVEIETVKLARSVFSKLHEICCSWVKDFPLRRRPQLYYETSIHAIKNM
RRKMEDKHVCIPDFNMLFNLEDQEEQAYFAVFDGHGGVDAAIYASIHLHVNLVRQEMFPH
DPAEALCRAFRVTDERFVQKAARESLRCGTTGVVTFIRGNMLHVAWVGDSQVMLVRKGQA
VELMKPHKPDREDEKQRIEALGGCVVWFGAWRVNGSLSVSRAIGDAEHKPYICGDADSAS
TVLDGTEDYLILACDGFYDTVNPDEAVKVVSDHLKENNGDSSMVAHKLVASARDAGSSDN
ITVIVVFLRDMNKAVNVSEESDWTENSFQGGQEDGGDDKENHGECKRPWPQHQCSAPADL
GYDGRVDSFTDRTSLSPGSQINVLEDPGYLDLTQIEASKPHSAQFLLPVEMFGPGAPKKA
NLINELMMEKKSVQSSLPEWSGAGEFPTAFNLGSTGEQIYRMQSLSPVCSGLENEQFKSP
GNRVSRLSHLRHHYSKKWHRFRFNPKFYSFLSAQEPSHKIGTSLSSLTGSGKRNRIRSSL
PWRQNSWKGYSENMRKLRKTHDIPCPDLPWSYKIE
Function
Protein phosphatase that inactivates multifunctional CaM kinases such as CAMK4 and CAMK2. Dephosphorylates and inactivates PAK. May play a role in the inhibition of actin fiber stress breakdown and in morphological changes driven by TNK2/CDC42. Dephosphorylates PRKAA2.
Reactome Pathway
Negative regulation of NMDA receptor-mediated neuronal transmission (R-HSA-9617324 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colorectal carcinoma DIS5PYL0 Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Posttranslational Modification [3]
Testicular germ cell tumor DIS5RN24 Strong Genetic Variation [4]
Breast carcinoma DIS2UE88 moderate Posttranslational Modification [3]
Gastric cancer DISXGOUK moderate Altered Expression [5]
Stomach cancer DISKIJSX moderate Altered Expression [5]
Colorectal neoplasm DISR1UCN Disputed Biomarker [1]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas 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 1E (PPM1E). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Protein phosphatase 1E (PPM1E). [11]
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8 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 1E (PPM1E). [7]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Protein phosphatase 1E (PPM1E). [8]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Protein phosphatase 1E (PPM1E). [9]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Protein phosphatase 1E (PPM1E). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Protein phosphatase 1E (PPM1E). [12]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Protein phosphatase 1E (PPM1E). [13]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Protein phosphatase 1E (PPM1E). [14]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Protein phosphatase 1E (PPM1E). [10]
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⏷ Show the Full List of 8 Drug(s)

References

1 Genomic and epigenomic integration identifies a prognostic signature in colon cancer.Clin Cancer Res. 2011 Mar 15;17(6):1535-45. doi: 10.1158/1078-0432.CCR-10-2509. Epub 2011 Jan 28.
2 Functions and dysfunctions of Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) and CaMKP-N/PPM1E.Arch Biochem Biophys. 2018 Feb 15;640:83-92. doi: 10.1016/j.abb.2018.01.001. Epub 2018 Jan 6.
3 Methylation analysis of plasma cell-free DNA for breast cancer early detection using bisulfite next-generation sequencing.Tumour Biol. 2016 Oct;37(10):13111-13119. doi: 10.1007/s13277-016-5190-z. Epub 2016 Jul 23.
4 Meta-analysis identifies four new loci associated with testicular germ cell tumor.Nat Genet. 2013 Jun;45(6):680-5. doi: 10.1038/ng.2634. Epub 2013 May 12.
5 AMPK phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation.Oncotarget. 2017 May 9;8(19):31288-31296. doi: 10.18632/oncotarget.16126.
6 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.
7 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.
8 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.
9 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
10 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
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 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.
13 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
14 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.