Details of Drug Off-Target (DOT)

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

• DOT Name: Methyl-CpG-binding domain protein 6 (MBD6)
• Synonyms: Methyl-CpG-binding protein MBD6
• Gene Name: MBD6
• Related Disease:
  Autism
  Neoplasm
  Uterine fibroids
  Wilson disease
• UniProt ID: MBD6_HUMAN
• Sequence:
  MNGGNESSGADRAGGPVATSVPIGWQRCVREGAVLYISPSGTELSSLEQTRSYLLSDGTC
  KCGLECPLNVPKVFNFDPLAPVTPGGAGVGPASEEDMTKLCNHRRKAVAMATLYRSMETT
  CSHSSPGEGASPQMFHTVSPGPPSARPPCRVPPTTPLNGGPGSLPPEPPSVSQAFPTLAG
  PGGLFPPRLADPVPSGGSSSPRFLPRGNAPSPAPPPPPAISLNAPSYNWGAALRSSLVPS
  DLGSPPAPHASSSPPSDPPLFHCSDALTPPPLPPSNNLPAHPGPASQPPVSSATMHLPLV
  LGPLGGAPTVEGPGAPPFLASSLLSAAAKAQHPPLPPPSTLQGRRPRAQAPSASHSSSLR
  PSQRRPRRPPTVFRLLEGRGPQTPRRSRPRAPAPVPQPFSLPEPSQPILPSVLSLLGLPT
  PGPSHSDGSFNLLGSDAHLPPPPTLSSGSPPQPRHPIQPSLPGTTSGSLSSVPGAPAPPA
  ASKAPVVPSPVLQSPSEGLGMGAGPACPLPPLAGGEAFPFPSPEQGLALSGAGFPGMLGA
  LPLPLSLGQPPPSPLLNHSLFGVLTGGGGQPPPEPLLPPPGGPGPPLAPGEPEGPSLLVA
  SLLPPPPSDLLPPPSAPPSNLLASFLPLLALGPTAGDGEGSAEGAGGPSGEPFSGLGDLS
  PLLFPPLSAPPTLIALNSALLAATLDPPSGTPPQPCVLSAPQPGPPTSSVTTATTDPGAS
  SLGKAPSNSGRPPQLLSPLLGASLLGDLSSLTSSPGALPSLLQPPGPLLSGQLGLQLLPG
  GGAPPPLSEASSPLACLLQSLQIPPEQPEAPCLPPESPASALEPEPARPPLSALAPPHGS
  PDPPVPELLTGRGSGKRGRRGGGGLRGINGEARPARGRKPGSRREPGRLALKWGTRGGFN
  GQMERSPRRTHHWQHNGELAEGGAEPKDPPPPGPHSEDLKVPPGVVRKSRRGRRRKYNPT
  RNSNSSRQDITLEPSPTARAAVPLPPRARPGRPAKNKRRKLAP
• Function: Binds to heterochromatin. Does not interact with either methylated or unmethylated DNA (in vitro).
• KEGG Pathway: Polycomb repressive complex (hsa03083)
• Reactome Pathway: UCH proteinases (R-HSA-5689603)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[2]
Wilson disease	DISVS9H7	Limited	Biomarker	[3]

8 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 Methyl-CpG-binding domain protein 6 (MBD6).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Methyl-CpG-binding domain protein 6 (MBD6).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Methyl-CpG-binding domain protein 6 (MBD6).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Methyl-CpG-binding domain protein 6 (MBD6).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Methyl-CpG-binding domain protein 6 (MBD6).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Methyl-CpG-binding domain protein 6 (MBD6).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Methyl-CpG-binding domain protein 6 (MBD6).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Methyl-CpG-binding domain protein 6 (MBD6).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Methyl-CpG-binding domain protein 6 (MBD6).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Methyl-CpG-binding domain protein 6 (MBD6).	[11]

References

• [1] The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1.Autism Res. 2012 Dec;5(6):385-97. doi: 10.1002/aur.1251. Epub 2012 Oct 10.
• [2] The Expression of MBD6 Is Associated with Tumor Size in Uterine Leiomyomas.Genet Test Mol Biomarkers. 2019 Aug;23(8):523-532. doi: 10.1089/gtmb.2019.0070. Epub 2019 Jul 16.
• [3] Whole-exome sequencing identifies novel pathogenic variants across the ATP7B gene and some modifiers of Wilson's disease phenotype.Liver Int. 2019 Jan;39(1):177-186. doi: 10.1111/liv.13967. Epub 2018 Oct 8.
• [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] 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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.