Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQOV093)

DOT Name Probable ATP-dependent RNA helicase DDX4 (DDX4)
Synonyms EC 3.6.4.13; DEAD box protein 4; Vasa homolog
Gene Name DDX4
Related Disease
Advanced cancer ( )
Epithelial ovarian cancer ( )
Male infertility ( )
Neoplasm ( )
Oligospermia ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Plasma cell myeloma ( )
Teratoma ( )
Adult lymphoma ( )
Germ cell tumor ( )
leukaemia ( )
Leukemia ( )
Lymphoma ( )
Neuroblastoma ( )
Nongerminomatous germ cell tumor ( )
Pediatric lymphoma ( )
Seminoma ( )
UniProt ID
DDX4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.6.4.13
Pfam ID
PF00270 ; PF00271
Sequence
MGDEDWEAEINPHMSSYVPIFEKDRYSGENGDNFNRTPASSSEMDDGPSRRDHFMKSGFA
SGRNFGNRDAGECNKRDNTSTMGGFGVGKSFGNRGFSNSRFEDGDSSGFWRESSNDCEDN
PTRNRGFSKRGGYRDGNNSEASGPYRRGGRGSFRGCRGGFGLGSPNNDLDPDECMQRTGG
LFGSRRPVLSGTGNGDTSQSRSGSGSERGGYKGLNEEVITGSGKNSWKSEAEGGESSDTQ
GPKVTYIPPPPPEDEDSIFAHYQTGINFDKYDTILVEVSGHDAPPAILTFEEANLCQTLN
NNIAKAGYTKLTPVQKYSIPIILAGRDLMACAQTGSGKTAAFLLPILAHMMHDGITASRF
KELQEPECIIVAPTRELVNQIYLEARKFSFGTCVRAVVIYGGTQLGHSIRQIVQGCNILC
ATPGRLMDIIGKEKIGLKQIKYLVLDEADRMLDMGFGPEMKKLISCPGMPSKEQRQTLMF
SATFPEEIQRLAAEFLKSNYLFVAVGQVGGACRDVQQTVLQVGQFSKREKLVEILRNIGD
ERTMVFVETKKKADFIATFLCQEKISTTSIHGDREQREREQALGDFRFGKCPVLVATSVA
ARGLDIENVQHVINFDLPSTIDEYVHRIGRTGRCGNTGRAISFFDLESDNHLAQPLVKVL
TDAQQDVPAWLEEIAFSTYIPGFSGSTRGNVFASVDTRKGKSTLNTAGFSSSQAPNPVDD
ESWD
Function
ATP-dependent RNA helicase required during spermatogenesis. Required to repress transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Involved in the secondary piRNAs metabolic process, the production of piRNAs in fetal male germ cells through a ping-pong amplification cycle. Required for PIWIL2 slicing-triggered piRNA biogenesis: helicase activity enables utilization of one of the slice cleavage fragments generated by PIWIL2 and processing these pre-piRNAs into piRNAs.
Tissue Specificity Expressed only in ovary and testis. Expressed in migratory primordial germ cells in the region of the gonadal ridge in both sexes.
Reactome Pathway
RND3 GTPase cycle (R-HSA-9696264 )
PIWI-interacting RNA (piRNA) biogenesis (R-HSA-5601884 )

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [2]
Male infertility DISY3YZZ Strong Biomarker [3]
Neoplasm DISZKGEW Strong Altered Expression [4]
Oligospermia DIS6YJF3 Strong Altered Expression [5]
Ovarian cancer DISZJHAP Strong Biomarker [2]
Ovarian neoplasm DISEAFTY Strong Biomarker [2]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [1]
Teratoma DIS6ICY4 Strong Biomarker [6]
Adult lymphoma DISK8IZR Limited Altered Expression [7]
Germ cell tumor DIS62070 Limited Biomarker [7]
leukaemia DISS7D1V Limited Altered Expression [1]
Leukemia DISNAKFL Limited Altered Expression [1]
Lymphoma DISN6V4S Limited Altered Expression [7]
Neuroblastoma DISVZBI4 Limited Genetic Variation [8]
Nongerminomatous germ cell tumor DISQOQJU Limited Altered Expression [7]
Pediatric lymphoma DIS51BK2 Limited Altered Expression [7]
Seminoma DIS3J8LJ Limited Altered Expression [9]
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⏷ Show the Full List of 18 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Probable ATP-dependent RNA helicase DDX4 (DDX4). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Probable ATP-dependent RNA helicase DDX4 (DDX4). [11]
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References

1 Germline factor DDX4 functions in blood-derived cancer cell phenotypes.Cancer Sci. 2017 Aug;108(8):1612-1619. doi: 10.1111/cas.13299. Epub 2017 Jul 11.
2 Vitamin D and DDX4 regulate the proliferation and invasion of ovarian cancer cells.Oncol Lett. 2018 Jul;16(1):905-909. doi: 10.3892/ol.2018.8718. Epub 2018 May 16.
3 Differential expression of VASA gene in ejaculated spermatozoa from normozoospermic men and patients with oligozoospermia.Asian J Androl. 2007 May;9(3):339-44. doi: 10.1111/j.1745-7262.2007.00253.x.
4 Ovarian Cancer Stem Cells: Unraveling a Germline Connection.Stem Cells Dev. 2017 Dec 15;26(24):1781-1803. doi: 10.1089/scd.2017.0153. Epub 2017 Nov 28.
5 Discrimination and characterization of Sertoli cell-only syndrome in non-obstructive azoospermia using cell-free seminal DDX4.Reprod Biomed Online. 2016 Aug;33(2):189-96. doi: 10.1016/j.rbmo.2016.05.001. Epub 2016 May 10.
6 Generation and characterization of human cryptorchid-specific induced pluripotent stem cells from urine.Stem Cells Dev. 2013 Mar 1;22(5):717-25. doi: 10.1089/scd.2012.0260. Epub 2013 Jan 4.
7 VASA is a specific marker for both normal and malignant human germ cells.Lab Invest. 2002 Feb;82(2):159-66. doi: 10.1038/labinvest.3780408.
8 Replication of GWAS-identified neuroblastoma risk loci strengthens the role of BARD1 and affirms the cumulative effect of genetic variations on disease susceptibility.Carcinogenesis. 2013 Mar;34(3):605-11. doi: 10.1093/carcin/bgs380. Epub 2012 Dec 7.
9 Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas.Oncotarget. 2016 Apr 19;7(16):22439-47. doi: 10.18632/oncotarget.7074.
10 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.
11 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.