Details of Drug Off-Target (DOT)

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

DOT Name RNA-binding protein 25 (RBM25)
Synonyms Arg/Glu/Asp-rich protein of 120 kDa; RED120; Protein S164; RNA-binding motif protein 25; RNA-binding region-containing protein 7
Gene Name RBM25
Related Disease
Advanced cancer ( )
Acute myelogenous leukaemia ( )
Cardiac failure ( )
Congestive heart failure ( )
Prostate cancer ( )
Prostate carcinoma ( )
Malaria ( )
Arrhythmia ( )
Human papillomavirus infection ( )
UniProt ID
RBM25_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3V53
Pfam ID
PF01480 ; PF00076
Sequence
MSFPPHLNRPPMGIPALPPGIPPPQFPGFPPPVPPGTPMIPVPMSIMAPAPTVLVPTVSM
VGKHLGARKDHPGLKAKENDENCGPTTTVFVGNISEKASDMLIRQLLAKCGLVLSWKRVQ
GASGKLQAFGFCEYKEPESTLRALRLLHDLQIGEKKLLVKVDAKTKAQLDEWKAKKKASN
GNARPETVTNDDEEALDEETKRRDQMIKGAIEVLIREYSSELNAPSQESDSHPRKKKKEK
KEDIFRRFPVAPLIPYPLITKEDINAIEMEEDKRDLISREISKFRDTHKKLEEEKGKKEK
ERQEIEKERRERERERERERERREREREREREREREKEKERERERERDRDRDRTKERDRD
RDRERDRDRDRERSSDRNKDRSRSREKSRDRERERERERERERERERERERERERERERE
REREREKDKKRDREEDEEDAYERRKLERKLREKEAAYQERLKNWEIRERKKTREYEKEAE
REEERRREMAKEAKRLKEFLEDYDDDRDDPKYYRGSALQKRLRDREKEMEADERDRKREK
EELEEIRQRLLAEGHPDPDAELQRMEQEAERRRQPQIKQEPESEEEEEEKQEKEEKREEP
MEEEEEPEQKPCLKPTLRPISSAPSVSSASGNATPNTPGDESPCGIIIPHENSPDQQQPE
EHRPKIGLSLKLGASNSPGQPNSVKRKKLPVDSVFNKFEDEDSDDVPRKRKLVPLDYGED
DKNATKGTVNTEEKRKHIKSLIEKIPTAKPELFAYPLDWSIVDSILMERRIRPWINKKII
EYIGEEEATLVDFVCSKVMAHSSPQSILDDVAMVLDEEAEVFIVKMWRLLIYETEAKKIG
LVK
Function
RNA-binding protein that acts as a regulator of alternative pre-mRNA splicing. Involved in apoptotic cell death through the regulation of the apoptotic factor BCL2L1 isoform expression. Modulates the ratio of proapoptotic BCL2L1 isoform S to antiapoptotic BCL2L1 isoform L mRNA expression. When overexpressed, stimulates proapoptotic BCL2L1 isoform S 5'-splice site (5'-ss) selection, whereas its depletion caused the accumulation of antiapoptotic BCL2L1 isoform L. Promotes BCL2L1 isoform S 5'-ss usage through the 5'-CGGGCA-3' RNA sequence. Its association with LUC7L3 promotes U1 snRNP binding to a weak 5' ss in a 5'-CGGGCA-3'-dependent manner. Binds to the exonic splicing enhancer 5'-CGGGCA-3' RNA sequence located within exon 2 of the BCL2L1 pre-mRNA. Also involved in the generation of an abnormal and truncated splice form of SCN5A in heart failure.
KEGG Pathway
Spliceosome (hsa03040 )
Reactome Pathway
mRNA Splicing - Major Pathway (R-HSA-72163 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Biomarker [1]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [2]
Cardiac failure DISDC067 Strong Biomarker [3]
Congestive heart failure DIS32MEA Strong Biomarker [3]
Prostate cancer DISF190Y Strong Biomarker [4]
Prostate carcinoma DISMJPLE Strong Biomarker [4]
Malaria DISQ9Y50 Disputed Biomarker [5]
Arrhythmia DISFF2NI Limited Biomarker [6]
Human papillomavirus infection DISX61LX Limited Biomarker [7]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 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 RNA-binding protein 25 (RBM25). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of RNA-binding protein 25 (RBM25). [9]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of RNA-binding protein 25 (RBM25). [10]
Marinol DM70IK5 Approved Marinol increases the expression of RNA-binding protein 25 (RBM25). [11]
Selenium DM25CGV Approved Selenium decreases the expression of RNA-binding protein 25 (RBM25). [12]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of RNA-binding protein 25 (RBM25). [13]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of RNA-binding protein 25 (RBM25). [14]
Nicotine DMWX5CO Approved Nicotine increases the expression of RNA-binding protein 25 (RBM25). [15]
Piroxicam DMTK234 Approved Piroxicam decreases the expression of RNA-binding protein 25 (RBM25). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of RNA-binding protein 25 (RBM25). [10]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of RNA-binding protein 25 (RBM25). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of RNA-binding protein 25 (RBM25). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of RNA-binding protein 25 (RBM25). [21]
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⏷ Show the Full List of 13 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
DNCB DMDTVYC Phase 2 DNCB affects the binding of RNA-binding protein 25 (RBM25). [17]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of RNA-binding protein 25 (RBM25). [18]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of RNA-binding protein 25 (RBM25). [19]
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References

1 Cdc7-Dbf4-mediated phosphorylation of HSP90-S164 stabilizes HSP90-HCLK2-MRN complex to enhance ATR/ATM signaling that overcomes replication stress in cancer.Sci Rep. 2017 Dec 5;7(1):17024. doi: 10.1038/s41598-017-17126-2.
2 The splicing factor RBM25 controls MYC activity in acute myeloid leukemia.Nat Commun. 2019 Jan 11;10(1):172. doi: 10.1038/s41467-018-08076-y.
3 Role of RBM25/LUC7L3 in abnormal cardiac sodium channel splicing regulation in human heart failure.Circulation. 2011 Sep 6;124(10):1124-31. doi: 10.1161/CIRCULATIONAHA.111.044495. Epub 2011 Aug 22.
4 Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway.Oncogene. 2019 Apr;38(14):2516-2532. doi: 10.1038/s41388-018-0602-8. Epub 2018 Dec 7.
5 Purification of human malaria parasite hypoxanthine guanine xanthine phosphoribosyltransferase (HGXPRT) using immobilized Reactive Red 120.Protein Expr Purif. 2007 Mar;52(1):153-8. doi: 10.1016/j.pep.2006.09.014. Epub 2006 Oct 5.
6 Efficacy of angiotensin II type 1 receptor blockade on reperfusion-induced arrhythmias and mortality early after myocardial infarction is increased in transgenic rats with cardiac angiotensin II type 1 overexpression.J Cardiovasc Pharmacol. 2002 Apr;39(4):610-9. doi: 10.1097/00005344-200204000-00017.
7 HPV shapes tumor transcriptome by globally modifying the pool of RNA binding protein-binding motif.Aging (Albany NY). 2019 Apr 29;11(8):2430-2446. doi: 10.18632/aging.101927.
8 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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 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.
11 Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
12 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
13 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
14 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
15 Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
16 Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
17 Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
18 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
19 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.
20 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
21 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.