Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT78NNWY)

• DOT Name: RNA-binding protein Raly (RALY)
• Synonyms: Autoantigen p542; Heterogeneous nuclear ribonucleoprotein C-like 2; hnRNP core protein C-like 2; hnRNP associated with lethal yellow protein homolog
• Gene Name: RALY
• Related Disease:
  Advanced cancer
  Cutaneous squamous cell carcinoma
  Melanoma
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Lung adenocarcinoma
  Lung carcinoma
  Lung squamous cell carcinoma
  Non-insulin dependent diabetes
  Ovarian neoplasm
  Ovarian serous adenocarcinoma
  Prostate carcinoma
  Squamous cell carcinoma
  Vitiligo
  Basal cell carcinoma
  Basal cell neoplasm
  Colon adenocarcinoma
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: RALY_HUMAN
• PDB ID: 1WF1
• Pfam ID: PF00076
• Sequence:
  MSLKLQASNVTNKNDPKSINSRVFIGNLNTALVKKSDVETIFSKYGRVAGCSVHKGYAFV
  QYSNERHARAAVLGENGRVLAGQTLDINMAGEPKPDRPKGLKRAASAIYSGYIFDYDYYR
  DDFYDRLFDYRGRLSPVPVPRAVPVKRPRVTVPLVRRVKTNVPVKLFARSTAVTTSSAKI
  KLKSSELQAIKTELTQIKSNIDALLSRLEQIAAEQKANPDGKKKGDGGGAGGGGGGGGSG
  GGGSGGGGGGGSSRPPAPQENTTSEAGLPQGEARTRDDGDEEGLLTHSEEELEHSQDTDA
  DDGALQ
• Function: RNA-binding protein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the liver. Binds the lipid-responsive non-coding RNA LeXis and is required for LeXis-mediated effect on cholesterogenesis. May be a heterogeneous nuclear ribonucleoprotein (hnRNP).
• Tissue Specificity: Expressed in heart, brain, lung, liver, skeletal muscle, kidney and pancreas. Weakly expressed in placenta.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Cutaneous squamous cell carcinoma	DIS3LXUG	Definitive	Genetic Variation	[2]
Melanoma	DIS1RRCY	Definitive	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[4]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[5]
Colon cancer	DISVC52G	Strong	Genetic Variation	[5]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[5]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[5]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[5]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[5]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[5]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[5]
Lung squamous cell carcinoma	DISXPIBD	Strong	Genetic Variation	[5]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[6]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[5]
Ovarian serous adenocarcinoma	DISSU72Z	Strong	Genetic Variation	[5]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[5]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[7]
Vitiligo	DISR05SL	Strong	Genetic Variation	[8]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[9]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[9]
Colon adenocarcinoma	DISDRE0J	Limited	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[11]
Neoplasm	DISZKGEW	Limited	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	RNA-binding protein Raly (RALY) affects the response to substance of Methamphetamine.	[25]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of RNA-binding protein Raly (RALY).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RNA-binding protein Raly (RALY).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of RNA-binding protein Raly (RALY).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RNA-binding protein Raly (RALY).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA-binding protein Raly (RALY).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of RNA-binding protein Raly (RALY).	[18]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of RNA-binding protein Raly (RALY).	[19]
Selenium	DM25CGV	Approved	Selenium increases the expression of RNA-binding protein Raly (RALY).	[20]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RNA-binding protein Raly (RALY).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of RNA-binding protein Raly (RALY).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-binding protein Raly (RALY).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of RNA-binding protein Raly (RALY).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of RNA-binding protein Raly (RALY).	[22]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of RNA-binding protein Raly (RALY).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of RNA-binding protein Raly (RALY).	[17]

References

• [1] The hnRNP RALY regulates transcription and cell proliferation by modulating the expression of specific factors including the proliferation marker E2F1.J Biol Chem. 2017 Dec 1;292(48):19674-19692. doi: 10.1074/jbc.M117.795591. Epub 2017 Sep 27.
• [2] Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma.Nat Commun. 2016 Jul 18;7:12048. doi: 10.1038/ncomms12048.
• [3] Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma.Oncotarget. 2017 Mar 14;8(11):17586-17592. doi: 10.18632/oncotarget.15230.
• [4] Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.Carcinogenesis. 2014 May;35(5):1012-9. doi: 10.1093/carcin/bgt404. Epub 2013 Dec 9.
• [5] Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.Cancer Res. 2016 Sep 1;76(17):5103-14. doi: 10.1158/0008-5472.CAN-15-2980. Epub 2016 Apr 20.
• [6] Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.Nat Commun. 2018 Jul 27;9(1):2941. doi: 10.1038/s41467-018-04951-w.
• [7] Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma.J Invest Dermatol. 2016 May;136(5):930-937. doi: 10.1016/j.jid.2016.01.013. Epub 2016 Jan 29.
• [8] Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.
• [9] Combined analysis of keratinocyte cancers identifies novel genome-wide loci.Hum Mol Genet. 2019 Sep 15;28(18):3148-3160. doi: 10.1093/hmg/ddz121.
• [10] NONO and RALY proteins are required for YB-1 oxaliplatin induced resistance in colon adenocarcinoma cell lines.Mol Cancer. 2011 Nov 25;10:145. doi: 10.1186/1476-4598-10-145.
• [11] Overexpression of RALY promotes migration and predicts poor prognosis in hepatocellular carcinoma.Cancer Manag Res. 2018 Nov 9;10:5559-5572. doi: 10.2147/CMAR.S182996. eCollection 2018.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [13] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [14] 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.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] 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.
• [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] 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.
• [19] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [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] 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] 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.
• [24] 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.
• [25] Genome-wide association for methamphetamine dependence: convergent results from 2 samples. Arch Gen Psychiatry. 2008 Mar;65(3):345-55. doi: 10.1001/archpsyc.65.3.345.