Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6W67VM)

• DOT Name: RNA-binding protein 47 (RBM47)
• Synonyms: RNA-binding motif protein 47
• Gene Name: RBM47
• Related Disease:
  Colorectal carcinoma
  Juvenile idiopathic arthritis
  Metastatic malignant neoplasm
  Multiple endocrine neoplasia type 1
  Neoplasm
  Ulcerative colitis
  High blood pressure
  Lung adenocarcinoma
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Stomach cancer
• UniProt ID: RBM47_HUMAN
• PDB ID: 2DIS
• Pfam ID: PF00076
• Sequence:
  MTAEDSTAAMSSDSAAGSSAKVPEGVAGAPNEAALLALMERTGYSMVQENGQRKYGGPPP
  GWEGPHPQRGCEVFVGKIPRDVYEDELVPVFEAVGRIYELRLMMDFDGKNRGYAFVMYCH
  KHEAKRAVRELNNYEIRPGRLLGVCCSVDNCRLFIGGIPKMKKREEILEEIAKVTEGVLD
  VIVYASAADKMKNRGFAFVEYESHRAAAMARRKLMPGRIQLWGHQIAVDWAEPEIDVDED
  VMETVKILYVRNLMIETTEDTIKKSFGQFNPGCVERVKKIRDYAFVHFTSREDAVHAMNN
  LNGTELEGSCLEVTLAKPVDKEQYSRYQKAARGGGAAEAAQQPSYVYSCDPYTLAYYGYP
  YNALIGPNRDYFVKAGSIRGRGRGAAGNRAPGPRGSYLGGYSAGRGIYSRYHEGKGKQQE
  KGYELVPNLEIPTVNPVAIKPGTVAIPAIGAQYSMFPAAPAPKMIEDGKIHTVEHMISPI
  AVQPDPASAAAAAAAAAAAAAAVIPTVSTPPPFQGRPITPVYTVAPNVQRIPTAGIYGAS
  YVPFAAPATATIATLQKNAAAAAAMYGGYAGYIPQAFPAAAIQVPIPDVYQTY
• Function: Single-stranded RNA-binding protein that functions in a variety of RNA processes, including alternative splicing, RNA stabilization, and RNA editing. Functions as an enzyme-substrate adapter for the cytidine deaminase APOBEC1. With APOBEC1 forms an mRNA editing complex involved into cytidine to uridine editing of a variety of mRNA molecules. Through the binding of their 3'UTR, also stabilizes a variety of mRNAs and regulates the expression of genes such as the interferon alpha/beta receptor and interleukin-10. Also involved in the alternative splicing of several genes including TJP1. Binds the pre-mRNA (U)GCAUG consensus sequences in downstream intronic regions of alternative exons, regulating their exclusion and inclusion into mRNAs. Independently of its RNA-binding activity, could negatively regulate MAVS by promoting its lysosomal degradation.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[2]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[1]
Multiple endocrine neoplasia type 1	DIS0RJRK	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[5]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[6]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[7]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[8]
Lung cancer	DISCM4YA	Limited	Altered Expression	[8]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[8]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[8]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	RNA-binding protein 47 (RBM47) decreases the response to substance of Arsenic trioxide.	[25]

3 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 RNA-binding protein 47 (RBM47).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of RNA-binding protein 47 (RBM47).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RNA-binding protein 47 (RBM47).	[22]

14 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 RNA-binding protein 47 (RBM47).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RNA-binding protein 47 (RBM47).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of RNA-binding protein 47 (RBM47).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA-binding protein 47 (RBM47).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RNA-binding protein 47 (RBM47).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of RNA-binding protein 47 (RBM47).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of RNA-binding protein 47 (RBM47).	[17]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of RNA-binding protein 47 (RBM47).	[18]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of RNA-binding protein 47 (RBM47).	[19]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of RNA-binding protein 47 (RBM47).	[20]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RNA-binding protein 47 (RBM47).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of RNA-binding protein 47 (RBM47).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-binding protein 47 (RBM47).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of RNA-binding protein 47 (RBM47).	[24]

References

• [1] Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression.Sci Rep. 2017 Jul 5;7(1):4687. doi: 10.1038/s41598-017-04234-2.
• [2] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [3] Distinct genome-wide methylation patterns in sporadic and hereditary nonfunctioning pancreatic neuroendocrine tumors.Cancer. 2019 Apr 15;125(8):1247-1257. doi: 10.1002/cncr.31930. Epub 2019 Jan 8.
• [4] The RNA-binding protein RBM47 is a novel regulator of cell fate decisions by transcriptionally controlling the p53-p21-axis.Cell Death Differ. 2020 Apr;27(4):1274-1285. doi: 10.1038/s41418-019-0414-6. Epub 2019 Sep 11.
• [5] Post-transcriptional regulator Rbm47 elevates IL-10 production and promotes the immunosuppression of B cells.Cell Mol Immunol. 2019 Jun;16(6):580-589. doi: 10.1038/s41423-018-0041-z. Epub 2018 May 29.
• [6] Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.Nat Genet. 2016 Oct;48(10):1151-1161. doi: 10.1038/ng.3654. Epub 2016 Sep 12.
• [7] RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma.Oncogene. 2017 Aug 31;36(35):5083. doi: 10.1038/onc.2017.191. Epub 2017 Jun 12.
• [8] RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma.Oncogene. 2016 Sep 22;35(38):5000-9. doi: 10.1038/onc.2016.35. Epub 2016 Feb 29.
• [9] 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.
• [10] 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.
• [11] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [12] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [13] 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.
• [14] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [15] 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.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [18] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [19] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [20] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] 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.
• [23] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [24] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [25] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.