General Information of Drug Off-Target (DOT) (ID: OTWSL9JQ)

DOT Name U8 snoRNA-decapping enzyme (NUDT16)
Synonyms
EC 3.6.1.62; IDP phosphatase; IDPase; EC 3.6.1.64; Inosine diphosphate phosphatase; Nucleoside diphosphate-linked moiety X motif 16; Nudix motif 16; Nudix hydrolase 16; U8 snoRNA-binding protein H29K; m7GpppN-mRNA hydrolase
Gene Name NUDT16
Related Disease
Rift valley fever ( )
UniProt ID
NUD16_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2XSQ; 3COU; 3MGM; 5VY2; 5W6X; 5W6Z; 5WJI; 6B09; 6CO2; 6X7U; 6X7V
EC Number
3.6.1.62; 3.6.1.64
Pfam ID
PF00293
Sequence
MAGARRLELGEALALGSGWRHACHALLYAPDPGMLFGRIPLRYAILMQMRFDGRLGFPGG
FVDTQDRSLEDGLNRELREELGEAAAAFRVERTDYRSSHVGSGPRVVAHFYAKRLTLEEL
LAVEAGATRAKDHGLEVLGLVRVPLYTLRDGVGGLPTFLENSFIGSAREQLLEALQDLGL
LQSGSISGLKIPAHH
Function
RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. Part of the U8 snoRNP complex that is required for the accumulation of mature 5.8S and 28S rRNA. Has diphosphatase activity and removes m7G and/or m227G caps from U8 snoRNA and leaves a 5'monophosphate on the RNA. Catalyzes also the cleavage of the cap structure on mRNAs. Does not hydrolyze cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG). Also hydrolysis m7G- and m227G U3-capped RNAs but with less efficiencies. Has broad substrate specificity with manganese or cobalt as cofactor and can act on various RNA species. Binds to the U8 snoRNA; metal is not required for RNA-binding. May play a role in the regulation of snoRNAs and mRNAs degradation. Acts also as a phosphatase; hydrolyzes the non-canonical purine nucleotides inosine diphosphate (IDP) and deoxyinosine diphosphate (dITP) as well as guanosine diphosphate (GDP), deoxyguanosine diphosphate (dGDP), xanthine diphosphate (XDP), inosine triphosphate (ITP) and deoxyinosine triphosphate (ITP) to their respective monophosphate derivatives and does not distinguish between the deoxy- and ribose forms. The order of activity with different substrates is IDP > dIDP >> GDP = dGDP > XDP = ITP = dITP. Binds strongly to GTP, ITP and XTP. Participates in the hydrolysis of dIDP/IDP and probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions. Exhibits decapping activity towards NAD-capped RNAs and FAD-capped RNAs. Exhibits decapping activity towards dpCoA-capped RNAs in vitro.
Tissue Specificity Expressed strongly in lung, kidney, adrenal gland, testis, heart and brain.
KEGG Pathway
Purine metabolism (hsa00230 )
Metabolic pathways (hsa01100 )
Nucleotide metabolism (hsa01232 )
R. degradation (hsa03018 )
Reactome Pathway
Phosphate bond hydrolysis by NUDT proteins (R-HSA-2393930 )
BioCyc Pathway
MetaCyc:MONOMER-17869

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Rift valley fever DISG6CM2 Strong Altered Expression [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 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 U8 snoRNA-decapping enzyme (NUDT16). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of U8 snoRNA-decapping enzyme (NUDT16). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of U8 snoRNA-decapping enzyme (NUDT16). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of U8 snoRNA-decapping enzyme (NUDT16). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of U8 snoRNA-decapping enzyme (NUDT16). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of U8 snoRNA-decapping enzyme (NUDT16). [7]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of U8 snoRNA-decapping enzyme (NUDT16). [8]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of U8 snoRNA-decapping enzyme (NUDT16). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of U8 snoRNA-decapping enzyme (NUDT16). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of U8 snoRNA-decapping enzyme (NUDT16). [11]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of U8 snoRNA-decapping enzyme (NUDT16). [12]
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⏷ Show the Full List of 11 Drug(s)

References

1 Virus-induced translational arrest through 4EBP1/2-dependent decay of 5'-TOP mRNAs restricts viral infection.Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2920-9. doi: 10.1073/pnas.1418805112. Epub 2015 May 18.
2 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.
3 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.
4 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
9 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
10 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
11 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.
12 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.