Details of Drug Off-Target (DOT)

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

• DOT Name: RNA-binding protein 5 (RBM5)
• Synonyms: Protein G15; Putative tumor suppressor LUCA15; RNA-binding motif protein 5; Renal carcinoma antigen NY-REN-9
• Gene Name: RBM5
• Related Disease:
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  Adenocarcinoma
  Advanced cancer
  Azoospermia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Fibrosarcoma
  Non-small-cell lung cancer
  Small-cell lung cancer
  Bladder cancer
  Bladder transitional cell carcinoma
  Metastatic malignant neoplasm
  Prostate cancer
  Prostate carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Pancreatic cancer
• UniProt ID: RBM5_HUMAN
• PDB ID: 2LK0; 2LK1; 2LKZ; 5MF9; 5MFY; 7PCV; 7PDV
• Pfam ID: PF01585 ; PF17780 ; PF00076 ; PF00641
• Sequence:
  MGSDKRVSRTERSGRYGSIIDRDDRDERESRSRRRDSDYKRSSDDRRGDRYDDYRDYDSP
  ERERERRNSDRSEDGYHSDGDYGEHDYRHDISDERESKTIMLRGLPITITESDIREMMES
  FEGPQPADVRLMKRKTGVSRGFAFVEFYHLQDATSWMEANQKKLVIQGKHIAMHYSNPRP
  KFEDWLCNKCCLNNFRKRLKCFRCGADKFDSEQEVPPGTTESVQSVDYYCDTIILRNIAP
  HTVVDSIMTALSPYASLAVNNIRLIKDKQTQQNRGFAFVQLSSAMDASQLLQILQSLHPP
  LKIDGKTIGVDFAKSARKDLVLSDGNRVSAFSVASTAIAAAQWSSTQSQSGEGGSVDYSY
  LQPGQDGYAQYAQYSQDYQQFYQQQAGGLESDASSASGTAVTTTSAAVVSQSPQLYNQTS
  NPPGSPTEEAQPSTSTSTQAPAASPTGVVPGTKYAVPDTSTYQYDESSGYYYDPTTGLYY
  DPNSQYYYNSLTQQYLYWDGEKETYVPAAESSSHQQSGLPPAKEGKEKKEKPKSKTAQQI
  AKDMERWAKSLNKQKENFKNSFQPVNSLREEERRESAAADAGFALFEKKGALAERQQLIP
  ELVRNGDEENPLKRGLVAAYSGDSDNEEELVERLESEEEKLADWKKMACLLCRRQFPNKD
  ALVRHQQLSDLHKQNMDIYRRSRLSEQELEALELREREMKYRDRAAERREKYGIPEPPEP
  KRKKQFDAGTVNYEQPTKDGIDHSNIGNKMLQAMGWREGSGLGRKCQGITAPIEAQVRLK
  GAGLGAKGSAYGLSGADSYKDAVRKAMFARFTEME
• Function: Component of the spliceosome A complex. Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5' and 3' splice sites of the intron. May both positively and negatively regulate apoptosis by regulating the alternative splicing of several genes involved in this process, including FAS and CASP2/caspase-2. In the case of FAS, promotes exclusion of exon 6 thereby producing a soluble form of FAS that inhibits apoptosis. In the case of CASP2/caspase-2, promotes exclusion of exon 9 thereby producing a catalytically active form of CASP2/Caspase-2 that induces apoptosis.
• Tissue Specificity: Isoform 5 is widely expressed in normal tissues and is expressed at increased levels in T-leukemic cell lines.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[1]
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[2]
Lung cancer	DISCM4YA	Definitive	Biomarker	[3]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[3]
Lung neoplasm	DISVARNB	Definitive	Altered Expression	[4]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Azoospermia	DIS94181	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Fibrosarcoma	DISWX7MU	Strong	Altered Expression	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[9]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[10]
Bladder cancer	DISUHNM0	moderate	Biomarker	[11]
Bladder transitional cell carcinoma	DISNL46A	moderate	Altered Expression	[11]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[12]
Prostate cancer	DISF190Y	moderate	Altered Expression	[13]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[13]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[11]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[11]
Pancreatic cancer	DISJC981	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	RNA-binding protein 5 (RBM5) affects the response to substance of Fluorouracil.	[26]

9 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 5 (RBM5).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of RNA-binding protein 5 (RBM5).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of RNA-binding protein 5 (RBM5).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA-binding protein 5 (RBM5).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of RNA-binding protein 5 (RBM5).	[15]
Selenium	DM25CGV	Approved	Selenium increases the expression of RNA-binding protein 5 (RBM5).	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of RNA-binding protein 5 (RBM5).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of RNA-binding protein 5 (RBM5).	[24]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of RNA-binding protein 5 (RBM5).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of RNA-binding protein 5 (RBM5).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RNA-binding protein 5 (RBM5).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of RNA-binding protein 5 (RBM5).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of RNA-binding protein 5 (RBM5).	[23]

References

• [1] Long noncoding RNA SNHG7 represses the expression of RBM5 to strengthen metastasis of hepatocellular carcinoma.Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5699-5704. doi: 10.26355/eurrev_201907_18307.
• [2] miR-938 promotes cell proliferation by regulating RBM5 in lung adenocarcinoma cells.Cell Biol Int. 2020 Jan;44(1):295-305. doi: 10.1002/cbin.11233. Epub 2019 Sep 25.
• [3] Role of RNA-binding protein 5 in the diagnosis and chemotherapeutic response of lung cancer.Oncol Lett. 2019 Feb;17(2):2013-2019. doi: 10.3892/ol.2018.9818. Epub 2018 Dec 10.
• [4] RBM5/H37 tumor suppressor, located at the lung cancer hot spot 3p21.3, alters expression of genes involved in metastasis.Lung Cancer. 2010 Dec;70(3):253-62. doi: 10.1016/j.lungcan.2010.02.012. Epub 2010 Mar 24.
• [5] In vivo evidence that RBM5 is a tumour suppressor in the lung.Sci Rep. 2017 Nov 24;7(1):16323. doi: 10.1038/s41598-017-15874-9.
• [6] RBM5 is a male germ cell splicing factor and is required for spermatid differentiation and male fertility.PLoS Genet. 2013;9(7):e1003628. doi: 10.1371/journal.pgen.1003628. Epub 2013 Jul 25.
• [7] Expression of RBM5-related factors in primary breast tissue.J Cell Biochem. 2007 Apr 15;100(6):1440-58. doi: 10.1002/jcb.21134.
• [8] LUCA15, a putative tumour suppressor gene encoding an RNA-binding nuclear protein, is down-regulated in ras-transformed Rat-1 cells.Genes Cells. 2000 Oct;5(10):849-58. doi: 10.1046/j.1365-2443.2000.00370.x.
• [9] Lentiviral vector-mediated RBM5 overexpression downregulates EGFR expression in human non-small cell lung cancer cells.World J Surg Oncol. 2014 Dec 2;12:367. doi: 10.1186/1477-7819-12-367.
• [10] RBM10 promotes transformation-associated processes in small cell lung cancer and is directly regulated by RBM5.PLoS One. 2017 Jun 29;12(6):e0180258. doi: 10.1371/journal.pone.0180258. eCollection 2017.
• [11] Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/-catenin feedback loop.FASEB J. 2019 Oct;33(10):10973-10985. doi: 10.1096/fj.201900537R. Epub 2019 Jul 18.
• [12] Regulating RNA Binding Motif 5 Gene Expression- A Novel Therapeutic Target for Lung Cancer.J Environ Pathol Toxicol Oncol. 2017;36(2):99-105. doi: 10.1615/JEnvironPatholToxicolOncol.2017019366.
• [13] Long noncoding RNA AFAP1-AS1 accelerates the proliferation and metastasis of prostate cancer via inhibiting RBM5 expression.Eur Rev Med Pharmacol Sci. 2019 Apr;23(8):3284-3290. doi: 10.26355/eurrev_201904_17690.
• [14] Long noncoding RNA PCAT-1 accelerates the metastasis of pancreatic cancer by repressing RBM5.Eur Rev Med Pharmacol Sci. 2019 Sep;23(17):7350-7355. doi: 10.26355/eurrev_201909_18841.
• [15] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [16] 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.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [24] 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.
• [25] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.
• [26] Mechanistic and predictive profiling of 5-Fluorouracil resistance in human cancer cells. Cancer Res. 2004 Nov 15;64(22):8167-76. doi: 10.1158/0008-5472.CAN-04-0970.