Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ6WO7A)

• DOT Name: Mini-chromosome maintenance complex-binding protein (MCMBP)
• Synonyms: MCM-BP; MCM-binding protein
• Gene Name: MCMBP
• UniProt ID: MCMBP_HUMAN
• PDB ID: 4KG9
• Pfam ID: PF09739
• Sequence:
  MPCGEDWLSHPLGIVQGFFAQNGVNPDWEKKVIEYFKEKLKENNAPKWVPSLNEVPLHYL
  KPNSFVKFRCMIQDMFDPEFYMGVYETVNQNTKAHVLHFGKYRDVAECGPQQELDLNSPR
  NTTLERQTFYCVPVPGESTWVKEAYVNANQARVSPSTSYTPSRHKRSYEDDDDMDLQPNK
  QKDQHAGARQAGSVGGLQWCGEPKRLETEASTGQQLNSLNLSSPFDLNFPLPGEKGPACL
  VKVYEDWDCFKVNDILELYGILSVDPVLSILNNDERDASALLDPMECTDTAEEQRVHSPP
  ASLVPRIHVILAQKLQHINPLLPACLNKEESKTCKFVSSFMSELSPVRAELLGFLTHALL
  GDSLAAEYLILHLISTVYTRRDVLPLGKFTVNLSGCPRNSTFTEHLYRIIQHLVPASFRL
  QMTIENMNHLKFIPHKDYTANRLVSGLLQLPSNTSLVIDETLLEQGQLDTPGVHNVTALS
  NLITWQKVDYDFSYHQMEFPCNINVFITSEGRSLLPADCQIHLQPQLIPPNMEEYMNSLL
  SAVLPSVLNKFRIYLTLLRFLEYSISDEITKAVEDDFVEMRKNDPQSITADDLHQLLVVA
  RCLSLSAGQTTLSRERWLRAKQLESLRRTRLQQQKCVNGNEL
• Function: Associated component of the MCM complex that acts as a regulator of DNA replication. Binds to the MCM complex during late S phase and promotes the disassembly of the MCM complex from chromatin, thereby acting as a key regulator of pre-replication complex (pre-RC) unloading from replicated DNA. Can dissociate the MCM complex without addition of ATP; probably acts by destabilizing interactions of each individual subunits of the MCM complex. Required for sister chromatid cohesion.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Mini-chromosome maintenance complex-binding protein (MCMBP).	[13]

1 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 affects the phosphorylation of Mini-chromosome maintenance complex-binding protein (MCMBP).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.