Details of Drug Off-Target (DOT)

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

DOT Name E3 ubiquitin-protein ligase PPP1R11 (PPP1R11)
Synonyms EC 2.3.2.27; Hemochromatosis candidate gene V protein; HCG V; Protein phosphatase 1 regulatory subunit 11; Protein phosphatase inhibitor 3
Gene Name PPP1R11
Related Disease
Carcinoma of liver and intrahepatic biliary tract ( )
Liver cancer ( )
Myocardial infarction ( )
Primary cutaneous T-cell lymphoma ( )
Rheumatoid arthritis ( )
Acute liver failure ( )
Advanced cancer ( )
Bone osteosarcoma ( )
Cholangiocarcinoma ( )
Chondrosarcoma ( )
Chronic myelomonocytic leukemia ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal neoplasm ( )
Hemochromatosis ( )
Huntington disease ( )
Lung cancer ( )
Lung carcinoma ( )
Malignant soft tissue neoplasm ( )
Myelodysplastic syndrome ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Osteoarthritis ( )
Osteosarcoma ( )
Pancreatic cancer ( )
Pneumonia ( )
Pneumonitis ( )
Pulmonary fibrosis ( )
Sarcoma ( )
Spinal muscular atrophy ( )
Epithelial ovarian cancer ( )
Hepatocellular carcinoma ( )
Neuroblastoma ( )
AIDS-related lymphoma ( )
Colorectal carcinoma ( )
Hyperglycemia ( )
Keratoconjunctivitis sicca ( )
Nervous system inflammation ( )
UniProt ID
PP1RB_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
8DWK; 8DWL; 8U5G
EC Number
2.3.2.27
Pfam ID
PF07491
Sequence
MAEAGAGLSETVTETTVTVTTEPENRSLTIKLRKRKPEKKVEWTSDTVDNEHMGRRSSKC
CCIYEKPRAFGESSTESDEEEEEGCGHTHCVRGHRKGRRRATLGPTPTTPPQPPDPSQPP
PGPMQH
Function
Atypical E3 ubiquitin-protein ligase which ubiquitinates TLR2 at 'Lys-754' leading to its degradation by the proteasome. Plays a role in regulating inflammatory cytokine release and gram-positive bacterial clearance by functioning, in part, through the ubiquitination and degradation of TLR2. Inhibitor of protein phosphatase 1.
Tissue Specificity Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Definitive Biomarker [1]
Liver cancer DISDE4BI Definitive Biomarker [1]
Myocardial infarction DIS655KI Definitive Genetic Variation [2]
Primary cutaneous T-cell lymphoma DIS35WVW Definitive Biomarker [3]
Rheumatoid arthritis DISTSB4J Definitive Biomarker [4]
Acute liver failure DIS5EZKX Strong Biomarker [5]
Advanced cancer DISAT1Z9 Strong Altered Expression [6]
Bone osteosarcoma DIST1004 Strong Altered Expression [7]
Cholangiocarcinoma DIS71F6X Strong Biomarker [8]
Chondrosarcoma DIS4I7JB Strong Altered Expression [9]
Chronic myelomonocytic leukemia DISIL8UR Strong Biomarker [10]
Colon cancer DISVC52G Strong Biomarker [11]
Colon carcinoma DISJYKUO Strong Biomarker [11]
Colorectal neoplasm DISR1UCN Strong Biomarker [12]
Hemochromatosis DISAPY0H Strong Biomarker [13]
Huntington disease DISQPLA4 Strong Biomarker [14]
Lung cancer DISCM4YA Strong Altered Expression [15]
Lung carcinoma DISTR26C Strong Altered Expression [15]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [16]
Myelodysplastic syndrome DISYHNUI Strong Biomarker [10]
Neoplasm DISZKGEW Strong Biomarker [17]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [18]
Osteoarthritis DIS05URM Strong Genetic Variation [19]
Osteosarcoma DISLQ7E2 Strong Altered Expression [7]
Pancreatic cancer DISJC981 Strong Biomarker [20]
Pneumonia DIS8EF3M Strong Biomarker [21]
Pneumonitis DIS88E0K Strong Biomarker [21]
Pulmonary fibrosis DISQKVLA Strong Biomarker [22]
Sarcoma DISZDG3U Strong Biomarker [16]
Spinal muscular atrophy DISTLKOB Strong Biomarker [23]
Epithelial ovarian cancer DIS56MH2 moderate Biomarker [24]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [25]
Neuroblastoma DISVZBI4 moderate Biomarker [26]
AIDS-related lymphoma DISSLRAU Limited Biomarker [27]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [28]
Hyperglycemia DIS0BZB5 Limited Biomarker [29]
Keratoconjunctivitis sicca DISNOENH Limited Biomarker [30]
Nervous system inflammation DISB3X5A Limited Biomarker [31]
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⏷ Show the Full List of 38 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 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 E3 ubiquitin-protein ligase PPP1R11 (PPP1R11). [32]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of E3 ubiquitin-protein ligase PPP1R11 (PPP1R11). [33]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of E3 ubiquitin-protein ligase PPP1R11 (PPP1R11). [34]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of E3 ubiquitin-protein ligase PPP1R11 (PPP1R11). [35]
Decitabine DMQL8XJ Approved Decitabine affects the expression of E3 ubiquitin-protein ligase PPP1R11 (PPP1R11). [34]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of E3 ubiquitin-protein ligase PPP1R11 (PPP1R11). [38]
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⏷ Show the Full List of 6 Drug(s)
2 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 E3 ubiquitin-protein ligase PPP1R11 (PPP1R11). [36]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of E3 ubiquitin-protein ligase PPP1R11 (PPP1R11). [37]
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References

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19 miRNA-335-5p relieves chondrocyte inflammation by activating autophagy in osteoarthritis.Life Sci. 2019 Jun 1;226:164-172. doi: 10.1016/j.lfs.2019.03.071. Epub 2019 Apr 7.
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22 Autophagy Attenuates Angiotensin II-Induced Pulmonary Fibrosis by Inhibiting Redox Imbalance-Mediated NOD-Like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation.Antioxid Redox Signal. 2019 Feb 1;30(4):520-541. doi: 10.1089/ars.2017.7261. Epub 2018 May 7.
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24 BMS-536924 sensitizes human epithelial ovarian cancer cells to the PARP inhibitor, 3-aminobenzamide.Gynecol Oncol. 2009 Nov;115(2):193-8. doi: 10.1016/j.ygyno.2009.07.009. Epub 2009 Aug 21.
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27 Ribonucleotide reductase represents a novel therapeutic target in primary effusion lymphoma.Oncogene. 2017 Aug 31;36(35):5068-5074. doi: 10.1038/onc.2017.122. Epub 2017 May 1.
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29 Ampelopsin protects endothelial cells from hyperglycemia-induced oxidative damage by inducing autophagy via the AMPK signaling pathway.Biofactors. 2015 Nov-Dec;41(6):463-75. doi: 10.1002/biof.1248. Epub 2015 Dec 8.
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32 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
33 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.
34 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
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