Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNWY581)

• DOT Name: Probable ATP-dependent RNA helicase DDX31 (DDX31)
• Synonyms: EC 3.6.4.13; DEAD box protein 31; Helicain
• Gene Name: DDX31
• Related Disease:
  Clear cell renal carcinoma
  Medulloblastoma
  Renal cell carcinoma
  Advanced cancer
  Bladder cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: DDX31_HUMAN
• EC Number: 3.6.4.13
• Pfam ID: PF00270 ; PF13959 ; PF00271
• Sequence:
  MAPDLASQRHSESFPSVNSRPNVILPGREGRREGLPPGGGTRGSLVPTRPVPPSPAPLGT
  SPYSWSRSGPGRGGGAGSSRVPRGVPGPAVCAPGSLLHHASPTQTMAAADGSLFDNPRTF
  SRRPPAQASRQAKATKRKYQASSEAPPAKRRNETSFLPAKKTSVKETQRTFKGNAQKMFS
  PKKHSVSTSDRNQEERQCIKTSSLFKNNPDIPELHRPVVKQVQEKVFTSAAFHELGLHPH
  LISTINTVLKMSSMTSVQKQSIPVLLEGRDALVRSQTGSGKTLAYCIPVVQSLQAMESKI
  QRSDGPYALVLVPTRELALQSFDTVQKLLKPFTWIVPGVLMGGEKRKSEKARLRKGINIL
  ISTPGRLVDHIKSTKNIHFSRLRWLVFDEADRILDLGFEKDITVILNAVNAECQKRQNVL
  LSATLTEGVTRLADISLHDPVSISVLDKSHDQLNPKDKAVQEVCPPPAGDKLDSFAIPES
  LKQHVTVVPSKLRLVCLAAFILQKCKFEEDQKMVVFFSSCELVEFHYSLFLQTLLSSSGA
  PASGQLPSASMRLKFLRLHGGMEQEERTAVFQEFSHSRRGVLLCTDVAARGLDLPQVTWI
  VQYNAPSSPAEYIHRIGRTARIGCHGSSLLILAPSEAEYVNSLASHKINVSEIKMEDILC
  VLTRDDCFKGKRWGAQKSHAVGPQEIRERATVLQTVFEDYVHSSERRVSWAKKALQSFIQ
  AYATYPRELKHIFHVRSLHLGHVAKSFGLRDAPRNLSALTRKKRKAHVKRPDLHKKTQSK
  HSLAEILRSEYSSGMEADIAKVKKQNAPGEPGGRPLQHSLQPTPCFGRGKTLKWRKTQKG
  VQRDSKTSQKV
• Function: Probable ATP-dependent RNA helicase. Plays a role in ribosome biogenesis and TP53/p53 regulation through its interaction with NPM1.
• Tissue Specificity: Weakly or undetectably expressed in normal organs. Up-regulated in renal cell carcinoma.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[1]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[3]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[3]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[3]
Urinary bladder neoplasm	DIS7HACE	moderate	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Probable ATP-dependent RNA helicase DDX31 (DDX31).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Probable ATP-dependent RNA helicase DDX31 (DDX31).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Probable ATP-dependent RNA helicase DDX31 (DDX31).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Probable ATP-dependent RNA helicase DDX31 (DDX31).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Probable ATP-dependent RNA helicase DDX31 (DDX31).	[10]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Probable ATP-dependent RNA helicase DDX31 (DDX31).	[11]

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 DDX31 (DDX31).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Probable ATP-dependent RNA helicase DDX31 (DDX31).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Probable ATP-dependent RNA helicase DDX31 (DDX31).	[12]

References

• [1] DDX31 regulates the p53-HDM2 pathway and rRNA gene transcription through its interaction with NPM1 in renal cell carcinomas.Cancer Res. 2012 Nov 15;72(22):5867-77. doi: 10.1158/0008-5472.CAN-12-1645. Epub 2012 Sep 27.
• [2] RNA binding protein-mediated post-transcriptional gene regulation in medulloblastoma.Mol Cells. 2014 May;37(5):357-64. doi: 10.14348/molcells.2014.0008. Epub 2014 Mar 6.
• [3] A DDX31/Mutant-p53/EGFR Axis Promotes Multistep Progression of Muscle-Invasive Bladder Cancer.Cancer Res. 2018 May 1;78(9):2233-2247. doi: 10.1158/0008-5472.CAN-17-2528. Epub 2018 Feb 13.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] 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.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] 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.
• [9] 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.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [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.