Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOP4UCG)

• DOT Name: Probable ATP-dependent RNA helicase DHX35 (DHX35)
• Synonyms: EC 3.6.4.13; DEAH box protein 35
• Gene Name: DHX35
• UniProt ID: DHX35_HUMAN
• EC Number: 3.6.4.13
• Pfam ID: PF21010 ; PF04408 ; PF00271 ; PF07717
• Sequence:
  MAAPVGPVKFWRPGTEGPGVSISEERQSLAENSGTTVVYNPYAALSIEQQRQKLPVFKLR
  NHILYLIENYQTVVIVGETGCGKSTQIPQYLAEAGWTAEGRVVGVTQPRRVAAVTVAGRV
  AEERGAVLGHEVGYCIRFDDCTDQLATRIKFLTDGMLVREMMVDPLLTKYSVIMLDEAHE
  RTLYTDIAIGLLKKIQKKRGDLRLIVASATLDADKFRDFFNQNETSDPARDTCVILTVEG
  RTFPVDIFYLQSPVPDYIKSTVETVVKIHQTEGDGDVLAFLTGQEEVETVVSMLIEQARA
  LARTGMKRHLRVLPMYAGLPSFEQMKVFERVSRSVRKVIVATNVAETSITISGIVYVIDC
  GFVKLRAYNPRTAIECLVVVPVSQASANQRAGRGGRSRSGKCYRLYTEEAFDKLPQSTVP
  EMQRSNLAPVILQLKALGIDNVLRFHFMSPPPAQSMVQALELLYALGGLDKDCRLTEPLG
  MRIAEFPLNPMFAKMLLESGNFGCSQEILSIAAMMQIQNIFVVPPNQKSHAIRVHRKFAV
  EEGDHLTMLNIYEAFIKHNKDSKWCQEHFLNYKGLVRAATVREQLKKLLVKFQVPRKSSE
  GDPDLVLRCIVSGFFANAARFHSTGAYRTIRDDHELHIHPASVLYAEKPPRWVIYNEVIQ
  TSKYYMRDVTAIESAWLLELAPHFYQQGTHLSLKAKRAKVQDP
• Function: May be involved in pre-mRNA splicing.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) 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 DHX35 (DHX35).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Probable ATP-dependent RNA helicase DHX35 (DHX35).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable ATP-dependent RNA helicase DHX35 (DHX35).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Probable ATP-dependent RNA helicase DHX35 (DHX35).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Probable ATP-dependent RNA helicase DHX35 (DHX35).	[4]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Probable ATP-dependent RNA helicase DHX35 (DHX35).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Probable ATP-dependent RNA helicase DHX35 (DHX35).	[7]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [5] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [6] 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.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.