Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2084EJ)

• DOT Name: ATP-dependent RNA helicase DDX19B (DDX19B)
• Synonyms: EC 3.6.4.13; DEAD box RNA helicase DEAD5; DEAD box protein 19B
• Gene Name: DDX19B
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: DD19B_HUMAN
• PDB ID: 3EWS; 3FHC; 3FHT; 3FMO; 3FMP; 3G0H; 6B4I; 6B4J; 6B4K
• EC Number: 3.6.4.13
• Pfam ID: PF00270 ; PF00271
• Sequence:
  MATDSWALAVDEQEAAAESLSNLHLKEEKIKPDTNGAVVKTNANAEKTDEEEKEDRAAQS
  LLNKLIRSNLVDNTNQVEVLQRDPNSPLYSVKSFEELRLKPQLLQGVYAMGFNRPSKIQE
  NALPLMLAEPPQNLIAQSQSGTGKTAAFVLAMLSQVEPANKYPQCLCLSPTYELALQTGK
  VIEQMGKFYPELKLAYAVRGNKLERGQKISEQIVIGTPGTVLDWCSKLKFIDPKKIKVFV
  LDEADVMIATQGHQDQSIRIQRMLPRNCQMLLFSATFEDSVWKFAQKVVPDPNVIKLKRE
  EETLDTIKQYYVLCSSRDEKFQALCNLYGAITIAQAMIFCHTRKTASWLAAELSKEGHQV
  ALLSGEMMVEQRAAVIERFREGKEKVLVTTNVCARGIDVEQVSVVINFDLPVDKDGNPDN
  ETYLHRIGRTGRFGKRGLAVNMVDSKHSMNILNRIQEHFNKKIERLDTDDLDEIEKIAN
• Function: ATP-dependent RNA helicase involved in mRNA export from the nucleus. Rather than unwinding RNA duplexes, DDX19B functions as a remodeler of ribonucleoprotein particles, whereby proteins bound to nuclear mRNA are dissociated and replaced by cytoplasmic mRNA binding proteins.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  mR. surveillance pathway (hsa03015)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Prostate cancer	DISF190Y	Limited	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[3]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ATP-dependent RNA helicase DDX19B (DDX19B).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of ATP-dependent RNA helicase DDX19B (DDX19B).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ATP-dependent RNA helicase DDX19B (DDX19B).	[8]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of ATP-dependent RNA helicase DDX19B (DDX19B).	[9]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of ATP-dependent RNA helicase DDX19B (DDX19B).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of ATP-dependent RNA helicase DDX19B (DDX19B).	[7]

References

• [1] Translation termination depends on the sequential ribosomal entry of eRF1 and eRF3.Nucleic Acids Res. 2019 May 21;47(9):4798-4813. doi: 10.1093/nar/gkz177.
• [2] DEAD Box Protein 5 Inhibits Liver Tumorigenesis by Stimulating Autophagy via Interaction with p62/SQSTM1.Hepatology. 2019 Mar;69(3):1046-1063. doi: 10.1002/hep.30300. Epub 2019 Feb 8.
• [3] Construction of a lncRNA-PCG bipartite network and identification of cancer-related lncRNAs: a case study in prostate cancer.Mol Biosyst. 2015 Feb;11(2):384-93. doi: 10.1039/c4mb00439f. Epub 2014 Nov 11.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.