Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ7KMEY)

• DOT Name: Probable ATP-dependent RNA helicase DDX52 (DDX52)
• Synonyms: EC 3.6.4.13; ATP-dependent RNA helicase ROK1-like; DEAD box protein 52
• Gene Name: DDX52
• Related Disease:
  Prostate cancer
  Prostate carcinoma
• UniProt ID: DDX52_HUMAN
• PDB ID: 3DKP
• EC Number: 3.6.4.13
• Pfam ID: PF00270 ; PF00271
• Sequence:
  MDVHDLFRRLGAGAKFDTRRFSADAARFQIGKRKYDFDSSEVLQGLDFFGNKKSVPGVCG
  ASQTHQKPQNGEKKEESLTERKREQSKKKRKTMTSEIASQEEGATIQWMSSVEAKIEDKK
  VQRESKLTSGKLENLRKEKINFLRNKHKIHVQGTDLPDPIATFQQLDQEYKINSRLLQNI
  LDAGFQMPTPIQMQAIPVMLHGRELLASAPTGSGKTLAFSIPILMQLKQPANKGFRALII
  SPTRELASQIHRELIKISEGTGFRIHMIHKAAVAAKKFGPKSSKKFDILVTTPNRLIYLL
  KQDPPGIDLASVEWLVVDESDKLFEDGKTGFRDQLASIFLACTSHKVRRAMFSATFAYDV
  EQWCKLNLDNVISVSIGARNSAVETVEQELLFVGSETGKLLAVRELVKKGFNPPVLVFVQ
  SIERAKELFHELIYEGINVDVIHAERTQQQRDNTVHSFRAGKIWVLICTALLARGIDFKG
  VNLVINYDFPTSSVEYIHRIGRTGRAGNKGKAITFFTEDDKPLLRSVANVIQQAGCPVPE
  YIKGFQKLLSKQKKKMIKKPLERESISTTPKCFLEKAKDKQKKVTGQNSKKKVALEDKS
• Function: Required for efficient ribosome biogenesis. May control cell cycle progression by regulating translation of mRNAs that contain a terminal oligo pyrimidine (TOP) motif in their 5' UTRs, such as GTPBP4.
• Reactome Pathway:
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Probable ATP-dependent RNA helicase DDX52 (DDX52).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Probable ATP-dependent RNA helicase DDX52 (DDX52).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Probable ATP-dependent RNA helicase DDX52 (DDX52).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Probable ATP-dependent RNA helicase DDX52 (DDX52).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Probable ATP-dependent RNA helicase DDX52 (DDX52).	[10]

3 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 Probable ATP-dependent RNA helicase DDX52 (DDX52).	[3]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Probable ATP-dependent RNA helicase DDX52 (DDX52).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Probable ATP-dependent RNA helicase DDX52 (DDX52).	[9]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Probable ATP-dependent RNA helicase DDX52 (DDX52).	[7]

References

• [1] Hyaluronan stimulates transformation of androgen-independent prostate cancer.Carcinogenesis. 2007 Feb;28(2):310-20. doi: 10.1093/carcin/bgl134. Epub 2006 Jul 24.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [8] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [9] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.