Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT769EC5)

• DOT Name: DNA helicase B (HELB)
• Synonyms: hDHB; EC 3.6.4.12
• Gene Name: HELB
• Related Disease:
  Melanoma
  Crohn disease
  Multiple sclerosis
• UniProt ID: HELB_HUMAN
• PDB ID: 7XV1
• EC Number: 3.6.4.12
• Pfam ID: PF13604 ; PF13538
• Sequence:
  MARSSPYLRQLQGPLLPPRDLVEEDDDYLNDDVEEDEESVFIDAEELCSGGVKAGSLPGC
  LRVSICDENTQETCKVFGRFPITGAWWRVKVQVKPVVGSRSYQYQVQGFPSYFLQSDMSP
  PNQKHICALFLKECEVSSDDVNKFLTWVKEVSNYKNLNFENLRETLRTFHKETGRKDQKQ
  PTQNGQEELFLDNEMSLPLENTIPFRNVMTALQFPKIMEFLPVLLPRHFKWIIGSGSKEM
  LKEIEEILGTHPWKLGFSKITYREWKLLRCEASWIAFCQCESLLQLMTDLEKNALIMYSR
  LKQICREDGHTYVEVNDLTLTLSNHMSFHAASESLKFLKDIGVVTYEKSCVFPYDLYHAE
  RAIAFSICDLMKKPPWHLCVDVEKVLASIHTTKPENSSDDALNESKPDEVRLENPVDVVD
  TQDNGDHIWTNGENEINAEISEVQLDQDQVEVPLDRDQVAALEMICSNPVTVISGKGGCG
  KTTIVSRLFKHIEQLEEREVKKACEDFEQDQNASEEWITFTEQSQLEADKAIEVLLTAPT
  GKAAGLLRQKTGLHAYTLCQVNYSFYSWTQTMMTTNKPWKFSSVRVLVVDEGSLVSVGIF
  KSVLNLLCEHSKLSKLIILGDIRQLPSIEPGNLLKDLFETLKSRNCAIELKTNHRAESQL
  IVDNATRISRRQFPKFDAELNISDNPTLPISIQDKTFIFVRLPEEDASSQSSKTNHHSCL
  YSAVKTLLQENNLQNAKTSQFIAFRRQDCDLINDCCCKHYTGHLTKDHQSRLVFGIGDKI
  CCTRNAYLSDLLPENISGSQQNNDLDASSEDFSGTLPDFAKNKRDFESNVRLCNGEIFFI
  TNDVTDVTFGKRRSLTINNMAGLEVTVDFKKLMKYCRIKHAWARTIHTFQGSEEQTVVYV
  VGKAGRQHWQHVYTAVTRGRCRVYVIAEESQLRNAIMKNSFPRKTRLKHFLQSKLSSSGA
  PPADFPSPRKSSGDSGGPSTPSASPLPVVTDHAMTNDVTWSEASSPDERTLTFAERWQLS
  SPDGVDTDDDLPKSRASKRTCGVNDDESPSKIFMVGESPQVSSRLQNLRLNNLIPRQLFK
  PTDNQET
• Function: 5'-3' DNA helicase involved in DNA damage response by acting as an inhibitor of DNA end resection. Recruitment to single-stranded DNA (ssDNA) following DNA damage leads to inhibit the nucleases catalyzing resection, such as EXO1, BLM and DNA2, possibly via the 5'-3' ssDNA translocase activity of HELB. As cells approach S phase, DNA end resection is promoted by the nuclear export of HELB following phosphorylation. Acts independently of TP53BP1. Unwinds duplex DNA with 5'-3' polarity. Has single-strand DNA-dependent ATPase and DNA helicase activities. Prefers ATP and dATP as substrates. During S phase, may facilitate cellular recovery from replication stress.
• Tissue Specificity: Highly expressed in testis and thymus and weakly in liver, spleen, kidney and brain.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[2]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of DNA helicase B (HELB).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DNA helicase B (HELB).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DNA helicase B (HELB).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of DNA helicase B (HELB).	[7]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of DNA helicase B (HELB).	[8]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of DNA helicase B (HELB).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DNA helicase B (HELB).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA helicase B (HELB).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of DNA helicase B (HELB).	[12]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of DNA helicase B (HELB).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of DNA helicase B (HELB).	[14]

References

• [1] Identification of Catechol-Type Diphenylbutadiene as a Tyrosinase-Activated Pro-oxidative Chemosensitizer against Melanoma A375 Cells via Glutathione S-Transferase Inhibition.J Agric Food Chem. 2019 Aug 14;67(32):9060-9069. doi: 10.1021/acs.jafc.9b02875. Epub 2019 Aug 1.
• [2] Identifying candidate genes for discrimination of ulcerative colitis and Crohn's disease.Mol Biol Rep. 2014 Oct;41(10):6349-55. doi: 10.1007/s11033-014-3469-y. Epub 2014 Sep 3.
• [3] Size-selected silver nanoparticles for MALDI-TOF mass spectrometry of amyloid-beta peptides.Nanoscale. 2018 Nov 29;10(46):22044-22054. doi: 10.1039/c8nr07921h.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [8] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [9] 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.
• [10] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [11] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] 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.
• [14] 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.