Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY24L1F)

• DOT Name: RNA-binding protein with multiple splicing 2 (RBPMS2)
• Synonyms: RNA binding protein, mRNA processing factor 2
• Gene Name: RBPMS2
• Related Disease:
  Advanced cancer
  Gastrointestinal stromal tumour
  Hirschsprung disease
• UniProt ID: RBPS2_HUMAN
• PDB ID: 2M9K
• Pfam ID: PF00076
• Sequence:
  MSNLKPDGEHGGSTGTGSGAGSGGALEEEVRTLFVSGLPVDIKPRELYLLFRPFKGYEGS
  LIKLTARQPVGFVIFDSRAGAEAAKNALNGIRFDPENPQTLRLEFAKANTKMAKSKLMAT
  PNPSNVHPALGAHFIARDPYDLMGAALIPASPEAWAPYPLYTTELTPAISHAAFTYPTAT
  AAAAALHAQVRWYPSSDTTQQGWKYRQFC
• Function: RNA-binding protein involved in the regulation of smooth muscle cell differentiation and proliferation in the gastrointestinal system. Binds NOG mRNA, the major inhibitor of the bone morphogenetic protein (BMP) pathway. Mediates an increase of NOG mRNA levels, thereby contributing to the negative regulation of BMP signaling pathway and promoting reversible dedifferentiation and proliferation of smooth muscle cells. Acts as a pre-mRNA alternative splicing regulator. Mediates ACTN1 and FLNB alternative splicing. Likely binds to mRNA tandem CAC trinucleotide or CA dinucleotide motifs.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	moderate	Biomarker	[1]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Biomarker	[1]
Hirschsprung disease	DISUUSM1	moderate	Altered Expression	[2]

1 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 RNA-binding protein with multiple splicing 2 (RBPMS2).	[3]

15 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 RNA-binding protein with multiple splicing 2 (RBPMS2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[11]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[11]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of RNA-binding protein with multiple splicing 2 (RBPMS2).	[17]

References

• [1] High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors.Exp Mol Pathol. 2013 Apr;94(2):314-21. doi: 10.1016/j.yexmp.2012.12.004. Epub 2013 Jan 4.
• [2] The RNA-binding protein RBPMS2 regulates development of gastrointestinal smooth muscle.Gastroenterology. 2012 Sep;143(3):687-697.e9. doi: 10.1053/j.gastro.2012.05.047. Epub 2012 Jun 5.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] 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.
• [12] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [13] Integrated transcriptomic and metabolomic analyses to characterize the anti-cancer effects of (-)-epigallocatechin-3-gallate in human colon cancer cells. Toxicol Appl Pharmacol. 2020 Aug 15;401:115100. doi: 10.1016/j.taap.2020.115100. Epub 2020 Jun 6.
• [14] 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.
• [15] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [16] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [17] 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.