Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0KAY9G)

• DOT Name: Helicase MOV-10 (MOV10)
• Synonyms: EC 3.6.4.13; Armitage homolog; Moloney leukemia virus 10 protein
• Gene Name: MOV10
• Related Disease:
  Alzheimer disease
  Autism
  Glioma
  Hepatitis B virus infection
  Immunodeficiency
  leukaemia
  Leukemia
  Nervous system disease
  High blood pressure
  Chronic hepatitis B virus infection
• UniProt ID: MOV10_HUMAN
• EC Number: 3.6.4.13
• Pfam ID: PF13086 ; PF13087 ; PF21634 ; PF21635 ; PF21633 ; PF21632
• Sequence:
  MPSKFSCRQLREAGQCFESFLVVRGLDMETDRERLRTIYNRDFKISFGTPAPGFSSMLYG
  MKIANLAYVTKTRVRFFRLDRWADVRFPEKRRMKLGSDISKHHKSLLAKIFYDRAEYLHG
  KHGVDVEVQGPHEARDGQLLIRLDLNRKEVLTLRLRNGGTQSVTLTHLFPLCRTPQFAFY
  NEDQELPCPLGPGECYELHVHCKTSFVGYFPATVLWELLGPGESGSEGAGTFYIARFLAA
  VAHSPLAAQLKPMTPFKRTRITGNPVVTNRIEEGERPDRAKGYDLELSMALGTYYPPPRL
  RQLLPMLLQGTSIFTAPKEIAEIKAQLETALKWRNYEVKLRLLLHLEELQMEHDIRHYDL
  ESVPMTWDPVDQNPRLLTLEVPGVTESRPSVLRGDHLFALLSSETHQEDPITYKGFVHKV
  ELDRVKLSFSMSLLSRFVDGLTFKVNFTFNRQPLRVQHRALELTGRWLLWPMLFPVAPRD
  VPLLPSDVKLKLYDRSLESNPEQLQAMRHIVTGTTRPAPYIIFGPPGTGKTVTLVEAIKQ
  VVKHLPKAHILACAPSNSGADLLCQRLRVHLPSSIYRLLAPSRDIRMVPEDIKPCCNWDA
  KKGEYVFPAKKKLQEYRVLITTLITAGRLVSAQFPIDHFTHIFIDEAGHCMEPESLVAIA
  GLMEVKETGDPGGQLVLAGDPRQLGPVLRSPLTQKHGLGYSLLERLLTYNSLYKKGPDGY
  DPQFITKLLRNYRSHPTILDIPNQLYYEGELQACADVVDRERFCRWAGLPRQGFPIIFHG
  VMGKDEREGNSPSFFNPEEAATVTSYLKLLLAPSSKKGKARLSPRSVGVISPYRKQVEKI
  RYCITKLDRELRGLDDIKDLKVGSVEEFQGQERSVILISTVRSSQSFVQLDLDFNLGFLK
  NPKRFNVAVTRAKALLIIVGNPLLLGHDPDWKVFLEFCKENGGYTGCPFPAKLDLQQGQN
  LLQGLSKLSPSTSGPHSHDYLPQEREGEGGLSLQVEPEWRNEL
• Function: 5' to 3' RNA helicase that is involved in a number of cellular roles ranging from mRNA metabolism and translation, modulation of viral infectivity, inhibition of retrotransposition, or regulation of synaptic transmission. Plays an important role in innate antiviral immunity by promoting type I interferon production. Mechanistically, specifically uses IKKepsilon/IKBKE as the mediator kinase for IRF3 activation. Blocks HIV-1 virus replication at a post-entry step. Counteracts HIV-1 Vif-mediated degradation of APOBEC3G through its helicase activity by interfering with the ubiquitin-proteasome pathway. Inhibits also hepatitis B virus/HBV replication by interacting with HBV RNA and thereby inhibiting the early step of viral reverse transcription. Contributes to UPF1 mRNA target degradation by translocation along 3' UTRs. Required for microRNA (miRNA)-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC. In cooperation with FMR1, regulates miRNA-mediated translational repression by AGO2. Restricts retrotransposition of long interspersed element-1 (LINE-1) in cooperation with TUT4 and TUT7 counteracting the RNA chaperonne activity of L1RE1. Facilitates LINE-1 uridylation by TUT4 and TUT7. Required for embryonic viability and for normal central nervous system development and function. Plays two critical roles in early brain development: suppresses retroelements in the nucleus by directly inhibiting cDNA synthesis, while regulates cytoskeletal mRNAs to influence neurite outgrowth in the cytosol. May function as a messenger ribonucleoprotein (mRNP) clearance factor ; (Microbial infection) Required for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). Interacts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription.
• Reactome Pathway:
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  Oncogene Induced Senescence (R-HSA-2559585)
  Ca2+ pathway (R-HSA-4086398)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  MAPK6/MAPK4 signaling (R-HSA-5687128)
  Transcriptional Regulation by VENTX (R-HSA-8853884)
  Regulation of RUNX1 Expression and Activity (R-HSA-8934593)
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)
  Regulation of PTEN mRNA translation (R-HSA-8943723)
  Competing endogenous RNAs (ceRNAs) regulate PTEN translation (R-HSA-8948700)
  Transcriptional Regulation by MECP2 (R-HSA-8986944)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Regulation of MECP2 expression and activity (R-HSA-9022692)
  NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux (R-HSA-9029569)
  Regulation of CDH11 mRNA translation by microRNAs (R-HSA-9759811)
  Regulation of NPAS4 mRNA translation (R-HSA-9768778)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Autism	DISV4V1Z	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[3]
Immunodeficiency	DIS093I0	Strong	Biomarker	[4]
leukaemia	DISS7D1V	Strong	Biomarker	[4]
Leukemia	DISNAKFL	Strong	Biomarker	[4]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[1]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[5]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Altered Expression	[6]

4 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 Helicase MOV-10 (MOV10).	[7]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Helicase MOV-10 (MOV10).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Helicase MOV-10 (MOV10).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Helicase MOV-10 (MOV10).	[17]

9 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 Helicase MOV-10 (MOV10).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Helicase MOV-10 (MOV10).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Helicase MOV-10 (MOV10).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Helicase MOV-10 (MOV10).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Helicase MOV-10 (MOV10).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Helicase MOV-10 (MOV10).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Helicase MOV-10 (MOV10).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Helicase MOV-10 (MOV10).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Helicase MOV-10 (MOV10).	[19]

References

• [1] Mov10 suppresses retroelements and regulates neuronal development and function in the developing brain.BMC Biol. 2017 Jun 29;15(1):54. doi: 10.1186/s12915-017-0387-1.
• [2] MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change.J Exp Clin Cancer Res. 2019 Jan 8;38(1):9. doi: 10.1186/s13046-018-0990-1.
• [3] The MOV10 helicase restricts hepatitis B virus replication by inhibiting viral reverse transcription.J Biol Chem. 2019 Dec 20;294(51):19804-19813. doi: 10.1074/jbc.RA119.009435. Epub 2019 Nov 13.
• [4] Moloney leukemia virus 10 (MOV10) protein inhibits retrovirus replication.J Biol Chem. 2010 May 7;285(19):14346-55. doi: 10.1074/jbc.M110.109314. Epub 2010 Mar 9.
• [5] Interethnic analyses of blood pressure loci in populations of East Asian and European descent.Nat Commun. 2018 Nov 28;9(1):5052. doi: 10.1038/s41467-018-07345-0.
• [6] Altered mRNA levels of MOV10, A3G, and IFN- in patients with chronic hepatitis B.J Microbiol. 2014 Jun;52(6):510-4. doi: 10.1007/s12275-014-3467-8. Epub 2014 May 29.
• [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] 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.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] 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.
• [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.
• [14] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [15] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.