Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT97S0IH)

DOT Name	ATP-dependent RNA helicase DHX8 (DHX8)
Synonyms	EC 3.6.4.13; DEAH box protein 8; RNA helicase HRH1
Gene Name	DHX8
Related Disease	Hereditary breast ovarian cancer syndrome ( )
UniProt ID	DHX8_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2EQS; 3I4U; 5MQF; 5XJC; 6HYS; 6HYT; 6HYU; 6ICZ; 6QDV; 7W59; 7W5A; 7W5B; 8C6J
EC Number	3.6.4.13
Pfam ID	PF00270 ; PF21010 ; PF04408 ; PF00271 ; PF07717 ; PF00575
Sequence	MAVAVAMAGALIGSEPGPAEELAKLEYLSLVSKVCTELDNHLGINDKDLAEFVISLAEKN TTFDTFKASLVKNGAEFTDSLISNLLRLIQTMRPPAKPSTSKDPVVKPKTEKEKLKELFP VLCQPDNPSVRTMLDEDDVKVAVDVLKELEALMPSAAGQEKQRDAEHRDRTKKKKRSRSR DRNRDRDRDRERNRDRDHKRRHRSRSRSRSRTRERNKVKSRYRSRSRSQSPPKDRKDRDK YGERNLDRWRDKHVDRPPPEEPTIGDIYNGKVTSIMQFGCFVQLEGLRKRWEGLVHISEL RREGRVANVADVVSKGQRVKVKVLSFTGTKTSLSMKDVDQETGEDLNPNRRRNLVGETNE ETSMRNPDRPTHLSLVSAPEVEDDSLERKRLTRISDPEKWEIKQMIAANVLSKEEFPDFD EETGILPKVDDEEDEDLEIELVEEEPPFLRGHTKQSMDMSPIKIVKNPDGSLSQAAMMQS ALAKERRELKQAQREAEMDSIPMGLNKHWVDPLPDAEGRQIAANMRGIGMMPNDIPEWKK HAFGGNKASYGKKTQMSILEQRESLPIYKLKEQLVQAVHDNQILIVIGETGSGKTTQITQ YLAEAGYTSRGKIGCTQPRRVAAMSVAKRVSEEFGCCLGQEVGYTIRFEDCTSPETVIKY MTDGMLLRECLIDPDLTQYAIIMLDEAHERTIHTDVLFGLLKKTVQKRQDMKLIVTSATL DAVKFSQYFYEAPIFTIPGRTYPVEILYTKEPETDYLDASLITVMQIHLTEPPGDILVFL TGQEEIDTACEILYERMKSLGPDVPELIILPVYSALPSEMQTRIFDPAPPGSRKVVIATN IAETSLTIDGIYYVVDPGFVKQKVYNSKTGIDQLVVTPISQAQAKQRAGRAGRTGPGKCY RLYTERAYRDEMLTTNVPEIQRTNLASTVLSLKAMGINDLLSFDFMDAPPMETLITAMEQ LYTLGALDDEGLLTRLGRRMAEFPLEPMLCKMLIMSVHLGCSEEMLTIVSMLSVQNVFYR PKDKQALADQKKAKFHQTEGDHLTLLAVYNSWKNNKFSNPWCYENFIQARSLRRAQDIRK QMLGIMDRHKLDVVSCGKSTVRVQKAICSGFFRNAAKKDPQEGYRTLIDQQVVYIHPSSA LFNRQPEWVVYHELVLTTKEYMREVTTIDPRWLVEFAPAFFKVSDPTKLSKQKKQQRLEP LYNRYEEPNAWRISRAFRRR
Function	Involved in pre-mRNA splicing as component of the spliceosome. Facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome.
Tissue Specificity	Expressed in skin, cervix and nerve. Also expressed in the brain.
KEGG Pathway	Spliceosome (hsa03040 )
Reactome Pathway	mRNA Splicing - Major Pathway (R-HSA-72163 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance		REF
Hereditary breast ovarian cancer syndrome	DISWDUGU	moderate	Genetic Variation	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ATP-dependent RNA helicase DHX8 (DHX8).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP-dependent RNA helicase DHX8 (DHX8).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of ATP-dependent RNA helicase DHX8 (DHX8).	[5]
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4 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 ATP-dependent RNA helicase DHX8 (DHX8).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of ATP-dependent RNA helicase DHX8 (DHX8).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of ATP-dependent RNA helicase DHX8 (DHX8).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of ATP-dependent RNA helicase DHX8 (DHX8).	[8]
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References

1	A tandem duplication of BRCA1 exons 1-19 through DHX8 exon 2 in four families with hereditary breast and ovarian cancer syndrome.Breast Cancer Res Treat. 2018 Dec;172(3):561-569. doi: 10.1007/s10549-018-4957-x. Epub 2018 Sep 6.
2	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
3	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.
4	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.
5	Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
6	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.
7	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.
8	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.