Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRU71O4)

• DOT Name: Large ribosomal subunit protein eL6 (RPL6)
• Synonyms: 60S ribosomal protein L6; Neoplasm-related protein C140; Tax-responsive enhancer element-binding protein 107; TaxREB107
• Gene Name: RPL6
• Related Disease:
  Noonan syndrome
  Parkinson disease
  Paroxysmal nocturnal haemoglobinuria
  Gallbladder cancer
  Gallbladder carcinoma
  Gastric neoplasm
  Carcinoma
  Gastric cancer
  Stomach cancer
  Undifferentiated carcinoma
• UniProt ID: RL6_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5AJ0 ; 5LKS ; 5T2C ; 6IP5 ; 6IP6 ; 6IP8 ; 6LQM ; 6LSR ; 6LSS ; 6LU8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6W6L ; 6XA1 ; 6Y0G ; 6Y2L ; 6Y57 ; 6Y6X ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 7BHP ; 7F5S ; 7OW7 ; 7QVP ; 7XNX ; 7XNY ; 8A3D ; 8FKP ; 8FKQ ; 8FKR ; 8FKS ; 8FKT ; 8FKU ; 8FKV ; 8FKW ; 8FKX ; 8FKY ; 8FKZ ; 8FL0 ; 8FL2 ; 8FL3 ; 8FL4 ; 8FL6 ; 8FL7 ; 8FL9 ; 8FLA ; 8FLB ; 8FLC ; 8FLD ; 8FLE ; 8FLF ; 8G5Y ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8IDT ; 8IDY ; 8IE3 ; 8INE ; 8INF ; 8INK ; 8IPD ; 8IPX ; 8IPY ; 8IR1 ; 8IR3 ; 8JDJ ; 8JDK ; 8JDL ; 8JDM
• Pfam ID: PF01159 ; PF03868
• Sequence:
  MAGEKVEKPDTKEKKPEAKKVDAGGKVKKGNLKAKKPKKGKPHCSRNPVLVRGIGRYSRS
  AMYSRKAMYKRKYSAAKSKVEKKKKEKVLATVTKPVGGDKNGGTRVVKLRKMPRYYPTED
  VPRKLLSHGKKPFSQHVRKLRASITPGTILIILTGRHRGKRVVFLKQLASGLLLVTGPLV
  LNRVPLRRTHQKFVIATSTKIDISNVKIPKHLTDAYFKKKKLRKPRHQEGEIFDTEKEKY
  EITEQRKIDQKAVDSQILPKIKAIPQLQGYLRSVFALTNGIYPHKLVF
• Function: Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell ; (Microbial infection) Specifically binds to domain C of the Tax-responsive enhancer element in the long terminal repeat of HTLV-I.
• KEGG Pathway:
  Ribosome (hsa03010)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Peptide chain elongation (R-HSA-156902)
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)
  Viral mRNA Translation (R-HSA-192823)
  Selenocysteine synthesis (R-HSA-2408557)
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  Formation of a pool of free 40S subunits (R-HSA-72689)
  GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706)
  Eukaryotic Translation Termination (R-HSA-72764)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Response of EIF2AK4 (GCN2) to amino acid deficiency (R-HSA-9633012)
  Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) (R-HSA-975956)
  Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (R-HSA-975957)
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Noonan syndrome	DIS7Q7DN	Strong	Biomarker	[1]
Parkinson disease	DISQVHKL	Strong	Biomarker	[2]
Paroxysmal nocturnal haemoglobinuria	DISBHMYH	Strong	Altered Expression	[3]
Gallbladder cancer	DISXJUAF	Disputed	Biomarker	[4]
Gallbladder carcinoma	DISD6ACL	Disputed	Biomarker	[4]
Gastric neoplasm	DISOKN4Y	Disputed	Altered Expression	[5]
Carcinoma	DISH9F1N	Limited	Biomarker	[6]
Gastric cancer	DISXGOUK	Limited	Biomarker	[7]
Stomach cancer	DISKIJSX	Limited	Biomarker	[7]
Undifferentiated carcinoma	DISIAZST	Limited	Biomarker	[6]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Large ribosomal subunit protein eL6 (RPL6) decreases the response to substance of Doxorubicin.	[20]
Cisplatin	DMRHGI9	Approved	Large ribosomal subunit protein eL6 (RPL6) decreases the response to substance of Cisplatin.	[20]
Fluorouracil	DMUM7HZ	Approved	Large ribosomal subunit protein eL6 (RPL6) decreases the response to substance of Fluorouracil.	[20]
Etoposide	DMNH3PG	Approved	Large ribosomal subunit protein eL6 (RPL6) decreases the response to substance of Etoposide.	[20]
Artesunate	DMR27C8	Approved	Large ribosomal subunit protein eL6 (RPL6) decreases the response to substance of Artesunate.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Large ribosomal subunit protein eL6 (RPL6).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large ribosomal subunit protein eL6 (RPL6).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Large ribosomal subunit protein eL6 (RPL6).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein eL6 (RPL6).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Large ribosomal subunit protein eL6 (RPL6).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Large ribosomal subunit protein eL6 (RPL6).	[13]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Large ribosomal subunit protein eL6 (RPL6).	[10]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Large ribosomal subunit protein eL6 (RPL6).	[14]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Large ribosomal subunit protein eL6 (RPL6).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Large ribosomal subunit protein eL6 (RPL6).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein eL6 (RPL6).	[17]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Large ribosomal subunit protein eL6 (RPL6).	[18]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of Large ribosomal subunit protein eL6 (RPL6).	[19]
CATECHIN	DMY38SB	Investigative	CATECHIN increases the expression of Large ribosomal subunit protein eL6 (RPL6).	[19]

1 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 Large ribosomal subunit protein eL6 (RPL6).	[15]

References

• [1] The human ribosomal protein L6 gene in a critical region for Noonan syndrome.J Hum Genet. 2000;45(5):290-3. doi: 10.1007/s100380070018.
• [2] Quantitative proteomics of a presymptomatic A53T alpha-synuclein Drosophila model of Parkinson disease.Mol Cell Proteomics. 2008 Jul;7(7):1191-203. doi: 10.1074/mcp.M700467-MCP200. Epub 2008 Mar 18.
• [3] Paroxysmal nocturnal hemoglobinuria: Differential gene expression of EGR-1 and TAXREB107.Exp Hematol. 2002 Jan;30(1):18-25. doi: 10.1016/s0301-472x(01)00763-9.
• [4] NOP2/Sun RNA methyltransferase 2 promotes tumor progression via its interacting partner RPL6 in gallbladder carcinoma.Cancer Sci. 2019 Nov;110(11):3510-3519. doi: 10.1111/cas.14190. Epub 2019 Sep 23.
• [5] [Differential expression of RPL6/Taxreb107 in drug resistant gastric cancer cell line SGC7901/ADR and its correlation with multiple-drug resistance].Zhonghua Zhong Liu Za Zhi. 2003 Jan;25(1):21-5.
• [6] cDNA microarray profiling of rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 7,12-dimethylbenz[a]anthracene.Carcinogenesis. 2002 Oct;23(10):1561-8. doi: 10.1093/carcin/23.10.1561.
• [7] Circular RNA hsa_circ_0006848 Related to Ribosomal Protein L6 Acts as a Novel Biomarker for Early Gastric Cancer.Dis Markers. 2019 Sep 2;2019:3863458. doi: 10.1155/2019/3863458. eCollection 2019.
• [8] 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.
• [9] 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.
• [10] Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
• [11] 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.
• [12] Arsenic trioxide (As(2)O(3)) induced apoptosis and its mechanisms in a human esophageal squamous carcinoma cell line. Chin Med J (Engl). 2002 Feb;115(2):280-5.
• [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] Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
• [15] 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.
• [16] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [17] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [18] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [19] Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.
• [20] Regulation of multidrug resistance by ribosomal protein l6 in gastric cancer cells. Cancer Biol Ther. 2005 Feb;4(2):242-7. doi: 10.4161/cbt.4.2.1477. Epub 2005 Feb 20.
• [21] Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chem Biol Interact. 2010 Apr 15;185(1):42-52.