Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL5RWA8)

DOT Name Protein phosphatase 1 regulatory subunit 15B (PPP1R15B)
Gene Name PPP1R15B
Related Disease
Advanced cancer ( )
Microcephaly, short stature, and impaired glucose metabolism 2 ( )
Wolcott-Rallison syndrome ( )
Primary microcephaly-mild intellectual disability-young-onset diabetes syndrome ( )
Breast cancer ( )
Breast carcinoma ( )
Intellectual disability ( )
Isolated congenital microcephaly ( )
Neoplasm ( )
Type-1/2 diabetes ( )
UniProt ID
PR15B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4V0U; 4V0V; 4V0W; 4V0X
Pfam ID
PF10472 ; PF10488
Sequence
MEPGTGGSRKRLGPRAGFRFWPPFFPRRSQAGSSKFPTPLGPENSGNPTLLSSAQPETRV
SYWTKLLSQLLAPLPGLLQKVLIWSQLFGGMFPTRWLDFAGVYSALRALKGREKPAAPTA
QKSLSSLQLDSSDPSVTSPLDWLEEGIHWQYSPPDLKLELKAKGSALDPAAQAFLLEQQL
WGVELLPSSLQSRLYSNRELGSSPSGPLNIQRIDNFSVVSYLLNPSYLDCFPRLEVSYQN
SDGNSEVVGFQTLTPESSCLREDHCHPQPLSAELIPASWQGCPPLSTEGLPEIHHLRMKR
LEFLQQASKGQDLPTPDQDNGYHSLEEEHSLLRMDPKHCRDNPTQFVPAAGDIPGNTQES
TEEKIELLTTEVPLALEEESPSEGCPSSEIPMEKEPGEGRISVVDYSYLEGDLPISARPA
CSNKLIDYILGGASSDLETSSDPEGEDWDEEAEDDGFDSDSSLSDSDLEQDPEGLHLWNS
FCSVDPYNPQNFTATIQTAARIVPEEPSDSEKDLSGKSDLENSSQSGSLPETPEHSSGEE
DDWESSADEAESLKLWNSFCNSDDPYNPLNFKAPFQTSGENEKGCRDSKTPSESIVAISE
CHTLLSCKVQLLGSQESECPDSVQRDVLSGGRHTHVKRKKVTFLEEVTEYYISGDEDRKG
PWEEFARDGCRFQKRIQETEDAIGYCLTFEHRERMFNRLQGTCFKGLNVLKQC
Function Maintains low levels of EIF2S1 phosphorylation in unstressed cells by promoting its dephosphorylation by PP1.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Genetic Variation [1]
Microcephaly, short stature, and impaired glucose metabolism 2 DIS29AHP Strong Autosomal recessive [2]
Wolcott-Rallison syndrome DISKVKXN Strong Genetic Variation [3]
Primary microcephaly-mild intellectual disability-young-onset diabetes syndrome DISUJDOX Supportive Autosomal recessive [3]
Breast cancer DIS7DPX1 Limited Biomarker [4]
Breast carcinoma DIS2UE88 Limited Biomarker [4]
Intellectual disability DISMBNXP Limited Genetic Variation [5]
Isolated congenital microcephaly DISUXHZ6 Limited Biomarker [5]
Neoplasm DISZKGEW Limited Biomarker [4]
Type-1/2 diabetes DISIUHAP Limited Biomarker [6]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Josamycin DMKJ8LB Approved Protein phosphatase 1 regulatory subunit 15B (PPP1R15B) affects the response to substance of Josamycin. [21]
Afimoxifene DMFORDT Phase 2 Protein phosphatase 1 regulatory subunit 15B (PPP1R15B) affects the response to substance of Afimoxifene. [22]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [7]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [19]
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12 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 1 regulatory subunit 15B (PPP1R15B). [8]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [9]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [11]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [12]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [14]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [16]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [17]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [18]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of Protein phosphatase 1 regulatory subunit 15B (PPP1R15B). [20]
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⏷ Show the Full List of 12 Drug(s)

References

1 Infant acute lymphoblastic leukemia with t(11;16)(q23;p13.3) and lineage switch into acute monoblastic leukemia.Cancer Genet Cytogenet. 2006 Jul 15;168(2):146-9. doi: 10.1016/j.cancergencyto.2006.02.013.
2 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
3 A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly. Diabetes. 2015 Nov;64(11):3951-62. doi: 10.2337/db15-0477. Epub 2015 Jul 9.
4 Protein phosphatase 1, regulatory subunit 15B is a survival factor for ER-positive breast cancer.Int J Cancer. 2013 Jun 1;132(11):2714-9. doi: 10.1002/ijc.27945. Epub 2012 Dec 27.
5 Homozygous mutation in the eukaryotic translation initiation factor 2alpha phosphatase gene, PPP1R15B, is associated with severe microcephaly, short stature and intellectual disability.Hum Mol Genet. 2015 Nov 15;24(22):6293-300. doi: 10.1093/hmg/ddv337. Epub 2015 Aug 24.
6 Circulatory miR-98-5p levels are deregulated during diabetes and it inhibits proliferation and promotes apoptosis by targeting PPP1R15B in keratinocytes.RNA Biol. 2020 Feb;17(2):188-201. doi: 10.1080/15476286.2019.1673117. Epub 2019 Oct 15.
7 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.
8 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
9 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
10 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.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
13 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
14 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
15 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
16 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.
17 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
18 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
19 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.
20 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
21 A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.
22 Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2730-5. doi: 10.1073/pnas.1018872108. Epub 2011 Apr 11.