Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBTDR44)

• DOT Name: ATP-dependent RNA helicase DDX19A (DDX19A)
• Synonyms: EC 3.6.4.13; DDX19-like protein; DEAD box protein 19A
• Gene Name: DDX19A
• Related Disease:
  Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2
  Amyotrophic lateral sclerosis type 4
  Connective tissue disorder
  Hepatitis C virus infection
  Juvenile amyotrophic lateral sclerosis
  Systemic lupus erythematosus
  Werner syndrome
  Advanced cancer
  Systemic sclerosis
• UniProt ID: DD19A_HUMAN
• EC Number: 3.6.4.13
• Pfam ID: PF00270 ; PF00271
• Sequence:
  MATDSWALAVDEQEAAVKSMTNLQIKEEKVKADTNGIIKTSTTAEKTDEEEKEDRAAQSL
  LNKLIRSNLVDNTNQVEVLQRDPNSPLYSVKSFEELRLKPQLLQGVYAMGFNRPSKIQEN
  ALPMMLAEPPQNLIAQSQSGTGKTAAFVLAMLSRVEPSDRYPQCLCLSPTYELALQTGKV
  IEQMGKFYPELKLAYAVRGNKLERGQKISEQIVIGTPGTVLDWCSKLKFIDPKKIKVFVL
  DEADVMIATQGHQDQSIRIQRMLPRNCQMLLFSATFEDSVWKFAQKVVPDPNVIKLKREE
  ETLDTIKQYYVLCSSRDEKFQALCNLYGAITIAQAMIFCHTRKTASWLAAELSKEGHQVA
  LLSGEMMVEQRAAVIERFREGKEKVLVTTNVCARGIDVEQVSVVINFDLPVDKDGNPDNE
  TYLHRIGRTGRFGKRGLAVNMVDSKHSMNILNRIQEHFNKKIERLDTDDLDEIEKIAN
• Function: ATP-dependent RNA helicase involved in mRNA export from the nucleus. Rather than unwinding RNA duplexes, DDX19 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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	DIS84UUI	Definitive	Genetic Variation	[1]
Amyotrophic lateral sclerosis type 4	DISSDHYG	Strong	Genetic Variation	[2]
Connective tissue disorder	DISKXBS3	Strong	Biomarker	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[4]
Juvenile amyotrophic lateral sclerosis	DISKDZC9	Strong	Genetic Variation	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[3]
Werner syndrome	DISZY45W	Strong	Genetic Variation	[5]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[6]
Systemic sclerosis	DISF44L6	moderate	Biomarker	[5]

3 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 DDX19A (DDX19A).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of ATP-dependent RNA helicase DDX19A (DDX19A).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ATP-dependent RNA helicase DDX19A (DDX19A).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of ATP-dependent RNA helicase DDX19A (DDX19A).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP-dependent RNA helicase DDX19A (DDX19A).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of ATP-dependent RNA helicase DDX19A (DDX19A).	[10]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of ATP-dependent RNA helicase DDX19A (DDX19A).	[11]

References

• [1] Ataxia with oculomotor apraxia type 2 fibroblasts exhibit increased susceptibility to oxidative DNA damage.J Clin Neurosci. 2014 Sep;21(9):1627-31. doi: 10.1016/j.jocn.2013.11.048. Epub 2014 May 6.
• [2] DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am J Hum Genet. 2004 Jun;74(6):1128-35. doi: 10.1086/421054. Epub 2004 Apr 21.
• [3] Autoantibodies to a nucleolar RNA helicase protein in patients with connective tissue diseases.Arthritis Rheum. 1997 Aug;40(8):1487-92. doi: 10.1002/1529-0131(199708)40:8<1487::AID-ART18>3.0.CO;2-P.
• [4] Induction of cell-mediated immune responses in mice by DNA vaccines that express hepatitis C virus NS3 mutants lacking serine protease and NTPase/RNA helicase activities.PLoS One. 2014 Jun 5;9(6):e98877. doi: 10.1371/journal.pone.0098877. eCollection 2014.
• [5] Werner's syndrome: from clinics to genetics.Clin Exp Rheumatol. 2000 Nov-Dec;18(6):760-6.
• [6] Functionally relevant RNA helicase mutations in familial and sporadic myeloid malignancies.Cancer Cell. 2015 May 11;27(5):609-11. doi: 10.1016/j.ccell.2015.04.013.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [12] 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.
• [13] 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.