Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCRN5TB)

DOT Name 2',5'-phosphodiesterase 12 (PDE12)
Synonyms 2'-PDE; 2-PDE; EC 3.1.4.-; Mitochondrial deadenylase; EC 3.1.13.4
Gene Name PDE12
Related Disease
Adult glioblastoma ( )
Glioblastoma multiforme ( )
Respiratory syncytial virus infection ( )
UniProt ID
PDE12_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4Z0V; 4Z2B; 4ZKF
EC Number
3.1.13.4; 3.1.4.-
Pfam ID
PF03372 ; PF21171
Sequence
MWRLPGARAALRVIRTAVEKLSRAEAGSQTAAGAMERAVVRCVPSEPKLSLSFALADGSH
KNMQRDQSEPLGRVLSRIATNALKGHAKAAAAKKSRKSRPNASGGAACSGPGPEPAVFCE
PVVKLYYREEAVAEDVLNVDAWQDGAVLQIGDVKYKVERNPPAFTELQLPRYIMAGFPVC
PKLSLEFGDPASSLFRWYKEAKPGAAEPEVGVPSSLSPSSPSSSWTETDVEERVYTPSNA
DIGLRLKLHCTPGDGQRFGHSRELESVCVVEAGPGTCTFDHRHLYTKKVTEDALIRTVSY
NILADTYAQTEFSRTVLYPYCAPYALELDYRQNLIQKELTGYNADVICLQEVDRAVFSDS
LVPALEAFGLEGVFRIKQHEGLATFYRKSKFSLLSQHDISFYEALESDPLHKELLEKLVL
YPSAQEKVLQRSSVLQVSVLQSTKDSSKRICVANTHLYWHPKGGYIRLIQMAVALAHIRH
VSCDLYPGIPVIFCGDFNSTPSTGMYHFVINGSIPEDHEDWASNGEEERCNMSLTHFFKL
KSACGEPAYTNYVGGFHGCLDYIFIDLNALEVEQVIPLPSHEEVTTHQALPSVSHPSDHI
ALVCDLKWK
Function
Enzyme that cleaves 2',5'-phosphodiester bond linking adenosines of the 5'-triphosphorylated oligoadenylates, triphosphorylated oligoadenylates referred as 2-5A modulates the 2-5A system. Degrades triphosphorylated 2-5A to produce AMP and ATP. Also cleaves 3',5'-phosphodiester bond of oligoadenylates. Plays a role as a negative regulator of the 2-5A system that is one of the major pathways for antiviral and antitumor functions induced by interferons (IFNs). Suppression of this enzyme increases cellular 2-5A levels and decreases viral replication in cultured small-airway epithelial cells and Hela cells.
Tissue Specificity Ubiquitous.
Reactome Pathway
OAS antiviral response (R-HSA-8983711 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Strong Altered Expression [1]
Glioblastoma multiforme DISK8246 Strong Altered Expression [1]
Respiratory syncytial virus infection DIS7FWHY Limited Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of 2',5'-phosphodiesterase 12 (PDE12). [3]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of 2',5'-phosphodiesterase 12 (PDE12). [4]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of 2',5'-phosphodiesterase 12 (PDE12). [5]
Estradiol DMUNTE3 Approved Estradiol increases the expression of 2',5'-phosphodiesterase 12 (PDE12). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of 2',5'-phosphodiesterase 12 (PDE12). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of 2',5'-phosphodiesterase 12 (PDE12). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of 2',5'-phosphodiesterase 12 (PDE12). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of 2',5'-phosphodiesterase 12 (PDE12). [10]
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⏷ Show the Full List of 8 Drug(s)

References

1 Characterization of inhibitors of phosphodiesterase 1C on a human cellular system.FEBS J. 2007 Sep;274(18):4812-24. doi: 10.1111/j.1742-4658.2007.06001.x. Epub 2007 Aug 14.
2 The Role of Phosphodiesterase 12 (PDE12) as a Negative Regulator of the Innate Immune Response and the Discovery of Antiviral Inhibitors.J Biol Chem. 2015 Aug 7;290(32):19681-96. doi: 10.1074/jbc.M115.653113. Epub 2015 Jun 8.
3 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 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.
6 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
7 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.
8 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
9 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
10 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.