Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7GE3BN)

DOT Name Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10)
Synonyms MHC class I region proline-rich protein CAT53; PP1-binding protein of 114 kDa; Phosphatase 1 nuclear targeting subunit; Protein FB19; p99
Gene Name PPP1R10
Related Disease
Neoplasm ( )
Advanced cancer ( )
Breast neoplasm ( )
Rheumatoid arthritis ( )
Gallbladder cancer ( )
Gallbladder carcinoma ( )
Nasopharyngeal carcinoma ( )
Psoriatic arthritis ( )
UniProt ID
PP1RA_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6ZV2
Pfam ID
PF08711 ; PF00642
Sequence
MGSGPIDPKELLKGLDSFLNRDGEVKSVDGISKIFSLMKEARKMVSRCTYLNILLQTRSP
EILVKFIDVGGYKLLNNWLTYSKTTNNIPLLQQILLTLQHLPLTVDHLKQNNTAKLVKQL
SKSSEDEELRKLASVLVSDWMAVIRSQSSTQPAEKDKKKRKDEGKSRTTLPERPLTEVKA
ETRAEEAPEKKREKPKSLRTTAPSHAKFRSTGLELETPSLVPVKKNASTVVVSDKYNLKP
IPLKRQSNVAAPGDATPPAEKKYKPLNTTPNATKEIKVKIIPPQPMEGLGFLDALNSAPV
PGIKIKKKKKVLSPTAAKPSPFEGKTSTEPSTAKPSSPEPAPPSEAMDADRPGTPVPPVE
VPELMDTASLEPGALDAKPVESPGDPNQLTRKGRKRKSVTWPEEGKLREYFYFELDETER
VNVNKIKDFGEAAKREILSDRHAFETARRLSHDNMEEKVPWVCPRPLVLPSPLVTPGSNS
QERYIQAEREKGILQELFLNKESPHEPDPEPYEPIPPKLIPLDEECSMDETPYVETLEPG
GSGGSPDGAGGSKLPPVLANLMGSMGAGKGPQGPGGGGINVQEILTSIMGSPNSHPSEEL
LKQPDYSDKIKQMLVPHGLLGPGPIANGFPPGGPGGPKGMQHFPPGPGGPMPGPHGGPGG
PVGPRLLGPPPPPRGGDPFWDGPGDPMRGGPMRGGPGPGPGPYHRGRGGRGGNEPPPPPP
PFRGARGGRSGGGPPNGRGGPGGGMVGGGGHRPHEGPGGGMGNSSGHRPHEGPGGGMGSG
HRPHEGPGGSMGGGGGHRPHEGPGGGISGGSGHRPHEGPGGGMGAGGGHRPHEGPGGSMG
GSGGHRPHEGPGHGGPHGHRPHDVPGHRGHDHRGPPPHEHRGHDGPGHGGGGHRGHDGGH
SHGGDMSNRPVCRHFMMKGNCRYENNCAFYHPGVNGPPLP
Function
Scaffold protein which mediates the formation of the PTW/PP1 phosphatase complex by providing a binding platform to each component of the complex. The PTW/PP1 phosphatase complex plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Mediates interaction of WDR82 and PPP1CA. Inhibitor of PPP1CA and PPP1CC phosphatase activities. Has inhibitory activity on PPP1CA only when phosphorylated. Binds to mRNA, single-stranded DNA (ssDNA), poly(A) and poly(G) homopolymers.
Tissue Specificity Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Breast neoplasm DISNGJLM Strong Altered Expression [3]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [4]
Gallbladder cancer DISXJUAF Limited Altered Expression [5]
Gallbladder carcinoma DISD6ACL Limited Altered Expression [5]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [6]
Psoriatic arthritis DISLWTG2 Limited Genetic Variation [7]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 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 Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [8]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [9]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [11]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [12]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [13]
Selenium DM25CGV Approved Selenium increases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [15]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [16]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate increases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [17]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [18]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [15]
T83193 DMHO29Y Patented T83193 decreases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [21]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [22]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [23]
cinnamaldehyde DMZDUXG Investigative cinnamaldehyde decreases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [21]
Pyrrolidine dithiocarbamate DM5ZAS6 Investigative Pyrrolidine dithiocarbamate increases the expression of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [24]
------------------------------------------------------------------------------------
⏷ Show the Full List of 16 Drug(s)
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [14]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [19]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [20]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Serine/threonine-protein phosphatase 1 regulatory subunit 10 (PPP1R10). [20]
------------------------------------------------------------------------------------

References

1 Phosphatase 1 Nuclear Targeting Subunit (PNUTS) Regulates Aurora Kinases and Mitotic Progression.Mol Cancer Res. 2019 Jan;17(1):10-19. doi: 10.1158/1541-7786.MCR-17-0670. Epub 2018 Sep 6.
2 Phosphatase 1 Nuclear Targeting Subunit, a Novel DNA Repair Partner of PARP1.Cancer Res. 2019 May 15;79(10):2460-2461. doi: 10.1158/0008-5472.CAN-19-0798.
3 A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour progression.Nat Cell Biol. 2017 Sep;19(9):1105-1115. doi: 10.1038/ncb3595. Epub 2017 Aug 21.
4 REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
5 miR-34 is associated with poor prognosis of patients with gallbladder cancer through regulating telomere length in tumor stem cells.Tumour Biol. 2014 Feb;35(2):1503-10. doi: 10.1007/s13277-013-1207-z.
6 PNUTS mediates ionizing radiation-induced CNE-2 nasopharyngeal carcinoma cell migration, invasion, and epithelial-mesenchymal transition via the PI3K/AKT signaling pathway.Onco Targets Ther. 2019 Feb 15;12:1205-1214. doi: 10.2147/OTT.S188571. eCollection 2019.
7 Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.Ann Rheum Dis. 2019 Mar;78(3):e214158. doi: 10.1136/annrheumdis-2018-214158. Epub 2018 Dec 14.
8 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
9 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.
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 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
13 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.
14 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
15 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.
16 Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
17 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
18 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
19 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.
20 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.
21 Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair. Mutat Res. 2007 Mar 1;616(1-2):60-9. doi: 10.1016/j.mrfmmm.2006.11.022. Epub 2006 Dec 18.
22 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
23 In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
24 Effects of a redox-active agent on lymphocyte activation and early gene expression patterns. Free Radic Biol Med. 2004 Nov 15;37(10):1550-63.