Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVCN8K0)

• DOT Name: Large ribosomal subunit protein eL22 (RPL22)
• Synonyms: 60S ribosomal protein L22; EBER-associated protein; EAP; Epstein-Barr virus small RNA-associated protein; Heparin-binding protein HBp15
• Gene Name: RPL22
• Related Disease:
  Adult lymphoma
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Lymphoma
  Pediatric lymphoma
  T-cell acute lymphoblastic leukaemia
  T-cell lymphoma
  Thymus cancer
  Acute lymphocytic leukaemia
  Endometrial cancer
  Endometrial carcinoma
  Herpes simplex infection
  Lung cancer
  Lung carcinoma
  Myelodysplastic syndrome
  Prostate cancer
  Prostate carcinoma
  Thymus lymphoma
  Colorectal carcinoma
  Melanoma
  Non-small-cell lung cancer
  Streptococcal pneumonia
• UniProt ID: RL22_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5AJ0 ; 5LKS ; 5T2C ; 6IP5 ; 6IP6 ; 6IP8 ; 6LQM ; 6LSR ; 6LSS ; 6LU8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6W6L ; 6Y0G ; 6Y2L ; 6Y57 ; 6Y6X ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 7BHP ; 7F5S ; 7QVP ; 7XNX ; 7XNY ; 8A3D ; 8FKZ ; 8FL2 ; 8FL3 ; 8FL4 ; 8FL6 ; 8FL7 ; 8FL9 ; 8FLA ; 8FLB ; 8FLC ; 8FLD ; 8FLE ; 8FLF ; 8G5Y ; 8G5Z ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8IDT ; 8IDY ; 8IE3 ; 8INE ; 8INF ; 8INK ; 8IPD ; 8IPX ; 8IPY ; 8IR1 ; 8IR3 ; 8JDJ ; 8JDK ; 8JDL ; 8JDM
• Pfam ID: PF01776
• Sequence:
  MAPVKKLVVKGGKKKKQVLKFTLDCTHPVEDGIMDAANFEQFLQERIKVNGKAGNLGGGV
  VTIERSKSKITVTSEVPFSKRYLKYLTKKYLKKNNLRDWLRVVANSKESYELRYFQINQD
  EEEEEDED
• Function: Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
• 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

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Definitive	Biomarker	[1]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Definitive	Biomarker	[2]
Lymphoma	DISN6V4S	Definitive	Altered Expression	[1]
Pediatric lymphoma	DIS51BK2	Definitive	Biomarker	[1]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Biomarker	[1]
T-cell lymphoma	DISSXRTQ	Definitive	Biomarker	[1]
Thymus cancer	DIS0TBWN	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[3]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[4]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[4]
Herpes simplex infection	DISL1SAV	Strong	Altered Expression	[5]
Lung cancer	DISCM4YA	Strong	Altered Expression	[6]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[6]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[7]
Thymus lymphoma	DISJ17C5	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[8]
Melanoma	DIS1RRCY	Limited	Biomarker	[9]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[9]
Streptococcal pneumonia	DIS2EKMJ	Limited	Genetic Variation	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Large ribosomal subunit protein eL22 (RPL22).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large ribosomal subunit protein eL22 (RPL22).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein eL22 (RPL22).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Large ribosomal subunit protein eL22 (RPL22).	[14]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Large ribosomal subunit protein eL22 (RPL22).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Large ribosomal subunit protein eL22 (RPL22).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Large ribosomal subunit protein eL22 (RPL22).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Large ribosomal subunit protein eL22 (RPL22).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Large ribosomal subunit protein eL22 (RPL22).	[17]

References

• [1] Ribosomal Protein Rpl22 Controls the Dissemination of T-cell Lymphoma.Cancer Res. 2016 Jun 1;76(11):3387-96. doi: 10.1158/0008-5472.CAN-15-2698. Epub 2016 Apr 5.
• [2] Consistent intergenic splicing and production of multiple transcripts between AML1 at 21q22 and unrelated genes at 3q26 in (3;21)(q26;q22) translocations.Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4004-8. doi: 10.1073/pnas.91.9.4004.
• [3] Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B.Blood. 2012 Nov 1;120(18):3764-73. doi: 10.1182/blood-2012-03-415349. Epub 2012 Sep 13.
• [4] Frequent mutations in the RPL22 gene and its clinical and functional implications.Gynecol Oncol. 2013 Mar;128(3):470-4. doi: 10.1016/j.ygyno.2012.10.026. Epub 2012 Nov 2.
• [5] Association of herpes simplex virus regulatory protein ICP22 with transcriptional complexes containing EAP, ICP4, RNA polymerase II, and viral DNA requires posttranslational modification by the U(L)13 proteinkinase.J Virol. 1997 Feb;71(2):1133-9. doi: 10.1128/JVI.71.2.1133-1139.1997.
• [6] Down-regulation of ribosomal protein L22 in non-small cell lung cancer.Med Oncol. 2013;30(3):646. doi: 10.1007/s12032-013-0646-0. Epub 2013 Jun 25.
• [7] Identification of candidate diagnostic and prognostic biomarkers for human prostate cancer: RPL22L1 and RPS21.Med Oncol. 2019 May 14;36(6):56. doi: 10.1007/s12032-019-1283-z.
• [8] RPL22L1 induction in colorectal cancer is associated with poor prognosis and 5-FU resistance.PLoS One. 2019 Oct 3;14(10):e0222392. doi: 10.1371/journal.pone.0222392. eCollection 2019.
• [9] Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC.Cancer Immunol Res. 2017 May;5(5):417-424. doi: 10.1158/2326-6066.CIR-16-0325. Epub 2017 Apr 14.
• [10] Emergence of a Streptococcus pneumoniae isolate resistant to streptogramins by mutation in ribosomal protein L22 during pristinamycin therapy of pneumococcal pneumonia.J Antimicrob Chemother. 2007 May;59(5):1010-2. doi: 10.1093/jac/dkm041. Epub 2007 Apr 13.
• [11] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [12] 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.
• [13] 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.
• [14] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [15] Ornithine decarboxylase antizyme upregulates DNA-dependent protein kinase and enhances the nonhomologous end-joining repair of DNA double-strand breaks in human oral cancer cells. Biochemistry. 2007 Aug 7;46(31):8920-32. doi: 10.1021/bi7000328. Epub 2007 Jul 14.
• [16] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [17] 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.
• [18] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [19] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.