Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBVB3W5)

DOT Name Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38)
Synonyms EC 3.6.4.13; ATP-dependent RNA helicase DHX38; DEAH box protein 38
Gene Name DHX38
Related Disease
Retinitis pigmentosa 84 ( )
Coronary heart disease ( )
Retinitis pigmentosa ( )
UniProt ID
PRP16_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5YZG; 6ZYM; 7A5P
EC Number
3.6.4.13
Pfam ID
PF00270 ; PF21010 ; PF04408 ; PF00271 ; PF07717
Sequence
MGDTSEDASIHRLEGTDLDCQVGGLICKSKSAASEQHVFKAPAPRPSLLGLDLLASLKRR
EREEKDDGEDKKKSKVSSYKDWEESKDDQKDAEEEGGDQAGQNIRKDRHYRSARVETPSH
PGGVSEEFWERSRQRERERREHGVYASSKEEKDWKKEKSRDRDYDRKRDRDERDRSRHSS
RSERDGGSERSSRRNEPESPRHRPKDAATPSRSTWEEEDSGYGSSRRSQWESPSPTPSYR
DSERSHRLSTRDRDRSVRGKYSDDTPLPTPSYKYNEWADDRRHLGSTPRLSRGRGRREEG
EEGISFDTEEERQQWEDDQRQADRDWYMMDEGYDEFHNPLAYSSEDYVRRREQHLHKQKQ
KRISAQRRQINEDNERWETNRMLTSGVVHRLEVDEDFEEDNAAKVHLMVHNLVPPFLDGR
IVFTKQPEPVIPVKDATSDLAIIARKGSQTVRKHREQKERKKAQHKHWELAGTKLGDIMG
VKKEEEPDKAVTEDGKVDYRTEQKFADHMKRKSEASSEFAKKKSILEQRQYLPIFAVQQE
LLTIIRDNSIVIVVGETGSGKTTQLTQYLHEDGYTDYGMIGCTQPRRVAAMSVAKRVSEE
MGGNLGEEVGYAIRFEDCTSENTLIKYMTDGILLRESLREADLDHYSAIIMDEAHERSLN
TDVLFGLLREVVARRSDLKLIVTSATMDAEKFAAFFGNVPIFHIPGRTFPVDILFSKTPQ
EDYVEAAVKQSLQVHLSGAPGDILIFMPGQEDIEVTSDQIVEHLEELENAPALAVLPIYS
QLPSDLQAKIFQKAPDGVRKCIVATNIAETSLTVDGIMFVIDSGYCKLKVFNPRIGMDAL
QIYPISQANANQRSGRAGRTGPGQCFRLYTQSAYKNELLTTTVPEIQRTNLANVVLLLKS
LGVQDLLQFHFMDPPPEDNMLNSMYQLWILGALDNTGGLTSTGRLMVEFPLDPALSKMLI
VSCDMGCSSEILLIVSMLSVPAIFYRPKGREEESDQIREKFAVPESDHLTYLNVYLQWKN
NNYSTIWCNDHFIHAKAMRKVREVRAQLKDIMVQQRMSLASCGTDWDIVRKCICAAYFHQ
AAKLKGIGEYVNIRTGMPCHLHPTSSLFGMGYTPDYIVYHELVMTTKEYMQCVTAVDGEW
LAELGPMFYSVKQAGKSRQENRRRAKEEASAMEEEMALAEEQLRARRQEQEKRSPLGSVR
STKIYTPGRKEQGEPMTPRRTPARFGL
Function Probable ATP-binding RNA helicase (Probable). Involved in pre-mRNA splicing as component of the spliceosome.
KEGG Pathway
Spliceosome (hsa03040 )
Reactome Pathway
mRNA Splicing - Major Pathway (R-HSA-72163 )
mRNA 3'-end processing (R-HSA-72187 )
RNA Polymerase II Transcription Termination (R-HSA-73856 )
Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Retinitis pigmentosa 84 DIS05ZKQ Strong Autosomal recessive [1]
Coronary heart disease DIS5OIP1 moderate Genetic Variation [2]
Retinitis pigmentosa DISCGPY8 Supportive Autosomal dominant [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [4]
Quercetin DM3NC4M Approved Quercetin decreases the phosphorylation of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [12]
TAK-243 DM4GKV2 Phase 1 TAK-243 affects the sumoylation of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [13]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [5]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [6]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [8]
Clozapine DMFC71L Approved Clozapine decreases the expression of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [9]
Haloperidol DM96SE0 Approved Haloperidol decreases the expression of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [9]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [10]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [11]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38). [14]
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⏷ Show the Full List of 8 Drug(s)

References

1 A missense mutation in the splicing factor gene DHX38 is associated with early-onset retinitis pigmentosa with macular coloboma. J Med Genet. 2014 Jul;51(7):444-8. doi: 10.1136/jmedgenet-2014-102316. Epub 2014 Apr 15.
2 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
3 Confirmation of the Role of DHX38 in the Etiology of Early-Onset Retinitis Pigmentosa. Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4552-4557. doi: 10.1167/iovs.18-23849.
4 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.
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 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.
7 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.
8 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
9 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
10 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
11 Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
12 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.
13 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
14 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.