Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT93XO40)

DOT Name ATP-dependent RNA helicase DDX42 (DDX42)
Synonyms EC 3.6.4.13; DEAD box protein 42; RNA helicase-like protein; RHELP; RNA helicase-related protein; RNAHP; SF3b DEAD box protein; Splicing factor 3B-associated 125 kDa protein; SF3b125
Gene Name DDX42
Related Disease
Medulloblastoma ( )
UniProt ID
DDX42_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7EVN; 8DPE; 8HK1
EC Number
3.6.4.13
Pfam ID
PF00270 ; PF00271
Sequence
MNWNKGGPGTKRGFGFGGFAISAGKKEEPKLPQQSHSAFGATSSSSGFGKSAPPQLPSFY
KIGSKRANFDEENAYFEDEEEDSSNVDLPYIPAENSPTRQQFHSKPVDSDSDDDPLEAFM
AEVEDQAARDMKRLEEKDKERKNVKGIRDDIEEEDDQEAYFRYMAENPTAGVVQEEEEDN
LEYDSDGNPIAPTKKIIDPLPPIDHSEIDYPPFEKNFYNEHEEITNLTPQQLIDLRHKLN
LRVSGAAPPRPGSSFAHFGFDEQLMHQIRKSEYTQPTPIQCQGVPVALSGRDMIGIAKTG
SGKTAAFIWPMLIHIMDQKELEPGDGPIAVIVCPTRELCQQIHAECKRFGKAYNLRSVAV
YGGGSMWEQAKALQEGAEIVVCTPGRLIDHVKKKATNLQRVSYLVFDEADRMFDMGFEYQ
VRSIASHVRPDRQTLLFSATFRKKIEKLARDILIDPIRVVQGDIGEANEDVTQIVEILHS
GPSKWNWLTRRLVEFTSSGSVLLFVTKKANAEELANNLKQEGHNLGLLHGDMDQSERNKV
ISDFKKKDIPVLVATDVAARGLDIPSIKTVINYDVARDIDTHTHRIGRTGRAGEKGVAYT
LLTPKDSNFAGDLVRNLEGANQHVSKELLDLAMQNAWFRKSRFKGGKGKKLNIGGGGLGY
RERPGLGSENMDRGNNNVMSNYEAYKPSTGAMGDRLTAMKAAFQSQYKSHFVAASLSNQK
AGSSAAGASGWTSAGSLNSVPTNSAQQGHNSPDSPVTSAAKGIPGFGNTGNISGAPVTYP
SAGAQGVNNTASGNNSREGTGGSNGKRERYTENRGSSRHSHGETGNRHSDSPRHGDGGRH
GDGYRHPESSSRHTDGHRHGENRHGGSAGRHGENRGANDGRNGESRKEAFNRESKMEPKM
EPKVDSSKMDKVDSKTDKTADGFAVPEPPKRKKSRWDS
Function
ATP-dependent RNA helicase that binds to partially double-stranded RNAs (dsRNAs) in order to unwind RNA secondary structures. Unwinding is promoted in the presence of single-strand binding proteins. Mediates also RNA duplex formation thereby displacing the single-strand RNA binding protein. ATP and ADP modulate its activity: ATP binding and hydrolysis by DDX42 triggers RNA strand separation, whereas the ADP-bound form of the protein triggers annealing of complementary RNA strands. Required for assembly of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs: DDX42 associates transiently with the SF3B subcomplex of the 17S U2 SnRNP complex and is released after fulfilling its role in the assembly of 17S U2 SnRNP. Involved in the survival of cells by interacting with TP53BP2 and thereby counteracting the apoptosis-stimulating activity of TP53BP2. Relocalizes TP53BP2 to the cytoplasm.
Tissue Specificity Expressed in several cell lines (at protein level). Expressed in liver, lung, tonsil, thymus, muscle and pancreatic islets.
KEGG Pathway
Spliceosome (hsa03040 )
Reactome Pathway
mRNA Splicing - Minor Pathway (R-HSA-72165 )
mRNA Splicing - Major Pathway (R-HSA-72163 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Medulloblastoma DISZD2ZL Strong Biomarker [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of ATP-dependent RNA helicase DDX42 (DDX42). [2]
Quercetin DM3NC4M Approved Quercetin decreases the phosphorylation of ATP-dependent RNA helicase DDX42 (DDX42). [4]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of ATP-dependent RNA helicase DDX42 (DDX42). [4]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of ATP-dependent RNA helicase DDX42 (DDX42). [10]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of ATP-dependent RNA helicase DDX42 (DDX42). [4]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of ATP-dependent RNA helicase DDX42 (DDX42). [3]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of ATP-dependent RNA helicase DDX42 (DDX42). [5]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of ATP-dependent RNA helicase DDX42 (DDX42). [6]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of ATP-dependent RNA helicase DDX42 (DDX42). [7]
Menadione DMSJDTY Approved Menadione increases the expression of ATP-dependent RNA helicase DDX42 (DDX42). [5]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of ATP-dependent RNA helicase DDX42 (DDX42). [8]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of ATP-dependent RNA helicase DDX42 (DDX42). [9]
PP-242 DM2348V Investigative PP-242 increases the expression of ATP-dependent RNA helicase DDX42 (DDX42). [11]
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⏷ Show the Full List of 8 Drug(s)

References

1 Interferon antagonist function of Japanese encephalitis virus NS4A and its interaction with DEAD-box RNA helicase DDX42.Virus Res. 2008 Oct;137(1):49-55. doi: 10.1016/j.virusres.2008.05.015. Epub 2008 Jul 10.
2 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.
3 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.
4 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.
5 Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
6 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
7 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
8 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
9 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
10 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
11 Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.