Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEHW1U2)

DOT Name Chromodomain-helicase-DNA-binding protein 6 (CHD6)
Synonyms CHD-6; EC 3.6.4.12; ATP-dependent helicase CHD6; Radiation-induced gene B protein
Gene Name CHD6
Related Disease
Cerebellar ataxia ( )
Influenza ( )
Neuroblastoma ( )
Prostate cancer ( )
Prostate neoplasm ( )
Tarsal-carpal coalition syndrome ( )
Transitional cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
UniProt ID
CHD6_HUMAN
PDB ID
2EPB
EC Number
3.6.4.12
Pfam ID
PF00385 ; PF00271 ; PF00176
Sequence
MKMKIQKKEKQLSNLKVLNHSPMSDASVNFDYKSPSPFDCSTDQEEKIEDVASHCLPQKD
LYTAEEEAATLFPRKMTSHNGMEDSGGGGTGVKKKRKKKEPGDQEGAAKGSKDREPKPKR
KREPKEPKEPRKAKEPKKAKEHKEPKQKDGAKKARKPREASGTKEAKEKRSCTDSAARTK
SRKASKEQGPTPVEKKKKGKRKSETTVESLELDQGLTNPSLRSPEESTESTDSQKRRSGR
QVKRRKYNEDLDFKVVDDDGETIAVLGAGRTSALSASTLAWQAEEPPEDDANIIEKILAS
KTVQEVHPGEPPFDLELFYVKYRNFSYLHCKWATMEELEKDPRIAQKIKRFRNKQAQMKH
IFTEPDEDLFNPDYVEVDRILEVAHTKDAETGEEVTHYLVKWCSLPYEESTWELEEDVDP
AKVKEFESLQVLPEIKHVERPASDSWQKLEKSREYKNSNQLREYQLEGMNWLLFNWYNRK
NCILADEMGLGKTIQSITFLSEIFLRGIHGPFLIIAPLSTITNWEREFRTWTEMNAIVYH
GSQISRQMIQQYEMVYRDAQGNPLSGVFKFHVVITTFEMILADCPELKKIHWSCVIIDEA
HRLKNRNCKLLEGLKLMALEHKVLLTGTPLQNSVEELFSLLNFLEPSQFPSETAFLEEFG
DLKTEEQVKKLQSILKPMMLRRLKDDVEKNLAPKQETIIEVELTNIQKKYYRAILEKNFS
FLTKGANQHNMPNLINTMMELRKCCNHPYLINGAEEKILEDFRKTHSPDAPDFQLQAMIQ
AAGKLVLIDKLLPKLIAGGHKVLIFSQMVRCLDILEDYLIQRRYTYERIDGRVRGNLRQA
AIDRFCKPDSDRFVFLLCTRAGGLGINLTAADTCIIFDSDWNPQNDLQAQARCHRIGQSK
AVKVYRLITRNSYEREMFDKASLKLGLDKAVLQDINRKGGTNGVQQLSKMEVEDLLRKGA
YGALMDEEDEGSKFCEEDIDQILQRRTHTITIQSEGKGSTFAKASFVASGNRTDISLDDP
NFWQKWAKIAELDTEAKNEKESLVIDRPRVRKQTKHYNSFEEDELMEFSELDSDSDERPT
RSRRLNDKARRYLRAECFRVEKNLLIFGWGRWKDILTHGRFKWHLNEKDMEMICRALLVY
CVKHYKGDEKIKSFIWELITPTKDGQAQTLQNHSGLSAPVPRGRKGKKTKNQLLIPELKD
ADWLATCNPEVVLHDDGYKKHLKQHCNKVLLRVRMLYYLKAEILGEAAEKAFEGSPAREL
DVPLPDIDYMEIPVDWWDAEADKSLLIGVFKHGYERYNAMRADPALCFLEKVGMPDEKSL
SAEQGVTDGTSDIPERGNTDKEDNAEDKVDGLQKQTESSSDGGDGVFSEKKDDSRAAQDG
SDPDKSPWPVSSALTARLRRLVTVYQRCNRKELCRPEILGPGNQGYWVQEEMFRRTSEMD
LINKEAQKRWTRREQADFYRTVSSFGVVYDQEKKTFDWTQFRIISRLDKKSDESLEQYFY
SFVAMCRNVCRLPTWKDGGPPDTTIYVEPITEERAARTLYRIELLRKVREQVLKCPQLHE
RLQLCRPSLYLPVWWECGKHDRDLLIGTAKHGLNRTDCYIMNDPQLSFLDAYRNYAQHKR
SGTQAPGNLCCLYQTNSKLYESLTYSQMSRTSESLENEPENLVRVESRDDHLSLPDVTCE
NFISKVQDVISINHDESLLPESLESMMYGKKVLSQEPSSFQESPSTNTESRKDVITISIS
KDGNCQSGGPEAEIASGPTFMGSLEAGGVAQANIKNGKHLLMSISKEGELCCSEAGQRPE
NIGQLEAKCLASPSLNPGNESGFVDMCSLSVCDSKRNLSSDQQLIDLLENKSLESKLILS
QNHSDEEEEEEENEEENLAMAVGMGERPEVLHLTEPTTNISREKNQGFQDETKKGSLEVA
NQTPGLQRAFPAPAACQCHCKHMERWMHGLENDEFEIEKPKAYIPDLFKSKTNTIAMEGE
PTAIPSQPFKVKHELLKEPWKESAEGQNVFPTYPLEGSELKSEDMDFENKDDYDRDGNCH
SQDYPGKYSEEESKSSTSGITGDIGDELQEARAPTIAQLLQEKTLYSFSEWPKDRVIINR
LDNICHVVLKGKWPSSQQYEPSGTLPTPVLTSSAGSRTSLSEPEAAEHSFSNGAALAAQI
HKESFLAPVFTKDEQKHRRPYEFEVERDAKARGLEQFSATHGHTPIILNGWHGESAMDLS
CSSEGSPGATSPFPVSASTPKIGAISSLQGALGMDLSGILQAGLIHPVTGQIVNGSLRRD
DAATRRRRGRRKHVEGGMDLIFLKEQTLQAGILEVHEDPGQATLSTTHPEGPGPATSAPE
PATAASSQAEKSIPSKSLLDWLRQQADYSLEVPGFGANFSDKPKQRRPRCKEPGKLDVSS
LSGEERVPAIPKEPGLRGFLPENKFNHTLAEPILRDTGPRRRGRRPRSELLKAPSIVADS
PSGMGPLFMNGLIAGMDLVGLQNMRNMPGIPLTGLVGFPAGFATMPTGEEVKSTLSMLPM
MLPGMAAVPQMFGVGGLLSPPMATTCTSTAPASLSSTTKSGTAVTEKTAEDKPSSHDVKT
DTLAEDKPGPGPFSDQSEPAITTSSPVAFNPFLIPGVSPGLIYPSMFLSPGMGMALPAMQ
QARHSEIVGLESQKRKKKKTKGDNPNSHPEPAPSCEREPSGDENCAEPSAPLPAEREHGA
QAGEGALKDSNNDTN
Function
DNA-dependent ATPase that plays a role in chromatin remodeling. Regulates transcription by disrupting nucleosomes in a largely non-sliding manner which strongly increases the accessibility of chromatin. Activates transcription of specific genes in response to oxidative stress through interaction with NFE2L2; (Microbial infection) Acts as a transcriptional repressor of different viruses including influenza virus or papillomavirus. During influenza virus infection, the viral polymerase complex localizes CHD6 to inactive chromatin where it gets degraded in a proteasome independent-manner.
Tissue Specificity Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cerebellar ataxia DIS9IRAV Strong Biomarker [1]
Influenza DIS3PNU3 Strong Biomarker [2]
Neuroblastoma DISVZBI4 Strong Biomarker [3]
Prostate cancer DISF190Y Strong Biomarker [4]
Prostate neoplasm DISHDKGQ Strong Biomarker [4]
Tarsal-carpal coalition syndrome DISY90L2 Strong Biomarker [5]
Transitional cell carcinoma DISWVVDR Limited Biomarker [5]
Urinary bladder cancer DISDV4T7 Limited Biomarker [5]
Urinary bladder neoplasm DIS7HACE Limited Biomarker [5]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Chromodomain-helicase-DNA-binding protein 6 (CHD6). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Chromodomain-helicase-DNA-binding protein 6 (CHD6). [10]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Chromodomain-helicase-DNA-binding protein 6 (CHD6). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Chromodomain-helicase-DNA-binding protein 6 (CHD6). [13]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Chromodomain-helicase-DNA-binding protein 6 (CHD6). [7]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Chromodomain-helicase-DNA-binding protein 6 (CHD6). [8]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Chromodomain-helicase-DNA-binding protein 6 (CHD6). [9]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Chromodomain-helicase-DNA-binding protein 6 (CHD6). [11]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Chromodomain-helicase-DNA-binding protein 6 (CHD6). [14]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Chromodomain-helicase-DNA-binding protein 6 (CHD6). [15]
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⏷ Show the Full List of 6 Drug(s)

References

1 Deletion of the Chd6 exon 12 affects motor coordination.Mamm Genome. 2010 Apr;21(3-4):130-42. doi: 10.1007/s00335-010-9248-8. Epub 2010 Jan 29.
2 CHD6 chromatin remodeler is a negative modulator of influenza virus replication that relocates to inactive chromatin upon infection.Cell Microbiol. 2011 Dec;13(12):1894-906. doi: 10.1111/j.1462-5822.2011.01679.x. Epub 2011 Sep 30.
3 CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas.J Natl Cancer Inst. 2008 Jul 2;100(13):940-9. doi: 10.1093/jnci/djn176. Epub 2008 Jun 24.
4 The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
5 Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder.Nat Genet. 2011 Aug 7;43(9):875-8. doi: 10.1038/ng.907.
6 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.
7 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
8 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
9 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
10 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
11 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
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.
13 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.
14 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
15 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.