Details of Drug Off-Target (DOT)

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

• DOT Name: RNA-binding protein 7 (RBM7)
• Synonyms: RNA-binding motif protein 7
• Gene Name: RBM7
• Related Disease:
  Non-small-cell lung cancer
  Pontocerebellar hypoplasia
  Spinal muscular atrophy
• UniProt ID: RBM7_HUMAN
• PDB ID: 2M8H; 5IQQ; 5LXR; 5LXY; 7S7B; 7S7C
• Pfam ID: PF00076
• Sequence:
  MGAAAAEADRTLFVGNLETKVTEELLFELFHQAGPVIKVKIPKDKDGKPKQFAFVNFKHE
  VSVPYAMNLLNGIKLYGRPIKIQFRSGSSHAPQDVSLSYPQHHVGNSSPTSTSPSRYERT
  MDNMTSSAQIIQRSFSSPENFQRQAVMNSALRQMSYGGKFGSSPLDQSGFSPSVQSHSHS
  FNQSSSSQWRQGTPSSQRKVRMNSYPYLADRHYSREQRYTDHGSDHHYRGKRDDFFYEDR
  NHDDWSHDYDNRRDSSRDGKWRSSRH
• Function: RNA-binding subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs. Binds preferentially polyuridine sequences and associates with newly synthesized RNAs, including pre-mRNAs and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and 3'-extended products from small nuclear RNAs (snRNAs). Participates in several biological processes including DNA damage response (DDR) and stress response. During stress response, activation of the p38MAPK-MK2 pathway decreases RBM7-RNA-binding and subsequently the RNA exosome degradation activities, thereby modulating the turnover of non-coding transcriptome. Participates in DNA damage response (DDR), through its interaction with MEPCE and LARP7, the core subunits of 7SK snRNP complex, that release the positive transcription elongation factor b (P-TEFb) complex from the 7SK snRNP. In turn, activation of P-TEFb complex induces the transcription of P-TEFb-dependent DDR genes to promote cell viability.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Pontocerebellar hypoplasia	DISRICMU	Strong	Biomarker	[2]
Spinal muscular atrophy	DISTLKOB	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Gefitinib	DM15F0X	Approved	RNA-binding protein 7 (RBM7) affects the response to substance of Gefitinib.	[1]

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 7 (RBM7).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of RNA-binding protein 7 (RBM7).	[17]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of RNA-binding protein 7 (RBM7).	[17]

14 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 7 (RBM7).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RNA-binding protein 7 (RBM7).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of RNA-binding protein 7 (RBM7).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA-binding protein 7 (RBM7).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RNA-binding protein 7 (RBM7).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RNA-binding protein 7 (RBM7).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of RNA-binding protein 7 (RBM7).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of RNA-binding protein 7 (RBM7).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RNA-binding protein 7 (RBM7).	[13]
Marinol	DM70IK5	Approved	Marinol decreases the expression of RNA-binding protein 7 (RBM7).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of RNA-binding protein 7 (RBM7).	[15]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of RNA-binding protein 7 (RBM7).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of RNA-binding protein 7 (RBM7).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of RNA-binding protein 7 (RBM7).	[19]

References

• [1] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.
• [2] Variants in EXOSC9 Disrupt the RNA Exosome and Result in Cerebellar Atrophy with Spinal Motor Neuronopathy. Am J Hum Genet. 2018 May 3;102(5):858-873. doi: 10.1016/j.ajhg.2018.03.011.
• [3] Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy.Hum Mol Genet. 2016 Jul 15;25(14):2985-2996. doi: 10.1093/hmg/ddw149. Epub 2016 May 18.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] 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.
• [14] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [17] 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.
• [18] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.