Details of Drug Off-Target (DOT)

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

• DOT Name: MRG/MORF4L-binding protein (MRGBP)
• Synonyms: MRG-binding protein; Up-regulated in colon cancer 4; Urcc4
• Gene Name: MRGBP
• Related Disease:
  Advanced cancer
  Adenoma
  Colorectal carcinoma
  Pancreatic cancer
  Cutaneous squamous cell carcinoma
  Neoplasm
• UniProt ID: MRGBP_HUMAN
• PDB ID: 2N1D
• Pfam ID: PF07904
• Sequence:
  MGEAEVGGGGAAGDKGPGEAATSPAEETVVWSPEVEVCLFHAMLGHKPVGVNRHFHMICI
  RDKFSQNIGRQVPSKVIWDHLSTMYDMQALHESEILPFPNPERNFVLPEEIIQEVREGKV
  MIEEEMKEEMKEDVDPHNGADDVFSSSGSLGKASEKSSKDKEKNSSDLGCKEGADKRKRS
  RVTDKVLTANSNPSSPSAAKRRRT
• Function: Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Genetic Variation	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Pancreatic cancer	DISJC981	moderate	Biomarker	[4]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Altered Expression	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of MRG/MORF4L-binding protein (MRGBP).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of MRG/MORF4L-binding protein (MRGBP).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of MRG/MORF4L-binding protein (MRGBP).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of MRG/MORF4L-binding protein (MRGBP).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of MRG/MORF4L-binding protein (MRGBP).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of MRG/MORF4L-binding protein (MRGBP).	[9]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of MRG/MORF4L-binding protein (MRGBP).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of MRG/MORF4L-binding protein (MRGBP).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of MRG/MORF4L-binding protein (MRGBP).	[14]

References

• [1] MRGBP as a potential biomarker for the malignancy of pancreatic ductal adenocarcinoma.Oncotarget. 2017 Jul 22;8(38):64224-64236. doi: 10.18632/oncotarget.19451. eCollection 2017 Sep 8.
• [2] Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression.Gut. 2009 Jan;58(1):79-89. doi: 10.1136/gut.2007.143065. Epub 2008 Oct 1.
• [3] MRG-binding protein contributes to colorectal cancer development.Cancer Sci. 2011 Aug;102(8):1486-92. doi: 10.1111/j.1349-7006.2011.01971.x. Epub 2011 Jun 9.
• [4] MiR-137 functions as a tumor suppressor in pancreatic cancer by targeting MRGBP.J Cell Biochem. 2018 Jun;119(6):4799-4807. doi: 10.1002/jcb.26676. Epub 2018 Mar 1.
• [5] Integrative mRNA profiling comparing cultured primary cells with clinical samples reveals PLK1 and C20orf20 as therapeutic targets in cutaneous squamous cell carcinoma.Oncogene. 2011 Nov 17;30(46):4666-77. doi: 10.1038/onc.2011.180. Epub 2011 May 23.
• [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] 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.
• [8] 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.
• [9] 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.
• [10] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [11] 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.
• [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] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.