Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3XKD6Y)

• DOT Name: Large ribosomal subunit protein uL10 (RPLP0)
• Synonyms: 60S acidic ribosomal protein P0; 60S ribosomal protein L10E
• Gene Name: RPLP0
• Related Disease:
  Astrocytoma
  Colon carcinoma
  Colorectal carcinoma
  Diabetic kidney disease
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Non-small-cell lung cancer
  Osteoporosis
  Systemic lupus erythematosus
  Asthma
  Neoplasm
  Osteoarthritis
• UniProt ID: RLA0_HUMAN
• PDB ID: 4V6W; 4V6X; 5AJ0; 6OLG; 6ZM7; 6ZME; 6ZMI; 6ZMO; 8G5Z; 8G60; 8G6J
• Pfam ID: PF00428 ; PF00466 ; PF17777
• Sequence:
  MPREDRATWKSNYFLKIIQLLDDYPKCFIVGADNVGSKQMQQIRMSLRGKAVVLMGKNTM
  MRKAIRGHLENNPALEKLLPHIRGNVGFVFTKEDLTEIRDMLLANKVPAAARAGAIAPCE
  VTVPAQNTGLGPEKTSFFQALGITTKISRGTIEILSDVQLIKTGDKVGASEATLLNMLNI
  SPFSFGLVIQQVFDNGSIYNPEVLDITEETLHSRFLEGVRNVASVCLQIGYPTVASVPHS
  IINGYKRVLALSVETDYTFPLAEKVKAFLADPSAFVAAAPVAAATTAAPAAAAAPAKVEA
  KEESEESDEDMGFGLFD
• Function: Ribosomal protein P0 is the functional equivalent of E.coli protein L10.
• 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)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  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

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Astrocytoma	DISL3V18	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[5]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Osteoporosis	DISF2JE0	Strong	Biomarker	[7]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[8]
Asthma	DISW9QNS	Limited	Altered Expression	[9]
Neoplasm	DISZKGEW	Limited	Altered Expression	[10]
Osteoarthritis	DIS05URM	Limited	Biomarker	[11]

13 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 uL10 (RPLP0).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[13]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[15]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[17]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[18]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[20]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[23]
9-hydroxyoctadecadienoic acid	DM0FWNJ	Investigative	9-hydroxyoctadecadienoic acid increases the expression of Large ribosomal subunit protein uL10 (RPLP0).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the phosphorylation of Large ribosomal subunit protein uL10 (RPLP0).	[19]

References

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• [2] Increased expression of human ribosomal phosphoprotein P0 messenger RNA in hepatocellular carcinoma and colon carcinoma.Cancer Res. 1992 Jun 1;52(11):3067-72.
• [3] Expression stability of common housekeeping genes is differently affected by bowel inflammation and cancer: implications for finding suitable normalizers for inflammatory bowel disease studies.Inflamm Bowel Dis. 2014 Jul;20(7):1147-56. doi: 10.1097/MIB.0000000000000067.
• [4] Investigation of mechanisms of mesenchymal stem cells for treatment of diabetic nephropathy via construction of a miRNA-TF-mRNA network.Ren Fail. 2018 Nov;40(1):136-145. doi: 10.1080/0886022X.2017.1421556. Epub 2018 Mar 13.
• [5] Expression and significance of tumor-related genes in HCC.World J Gastroenterol. 2005 Jul 7;11(25):3850-4. doi: 10.3748/wjg.v11.i25.3850.
• [6] Identification of suitable reference genes for gene expression studies using quantitative polymerase chain reaction in lung cancer in vitro.Mol Med Rep. 2015 May;11(5):3767-73. doi: 10.3892/mmr.2015.3159. Epub 2015 Jan 8.
• [7] Postmenopausal Osteoporosis reference genes for qPCR expression assays.Sci Rep. 2019 Nov 11;9(1):16533. doi: 10.1038/s41598-019-52612-9.
• [8] Screening epitopes on systemic lupus erythematosus autoantigens with a peptide array.Oncotarget. 2017 Sep 18;8(49):85559-85567. doi: 10.18632/oncotarget.20994. eCollection 2017 Oct 17.
• [9] Selection of suitable housekeeping genes for real-time quantitative PCR in CD4(+) lymphocytes from asthmatics with or without depression.PLoS One. 2012;7(10):e48367. doi: 10.1371/journal.pone.0048367. Epub 2012 Oct 24.
• [10] Estrogen, tamoxifen, and Akt modulate expression of putative housekeeping genes in breast cancer cells.J Steroid Biochem Mol Biol. 2011 Jul;125(3-5):219-25. doi: 10.1016/j.jsbmb.2011.03.005. Epub 2011 Mar 21.
• [11] Housekeeping gene validation for RT-qPCR studies on synovial fibroblasts derived from healthy and osteoarthritic patients with focus on mechanical loading.PLoS One. 2019 Dec 6;14(12):e0225790. doi: 10.1371/journal.pone.0225790. eCollection 2019.
• [12] 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.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene. 2001 Jan 10;262(1-2):207-14. doi: 10.1016/s0378-1119(00)00530-8.
• [15] 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.
• [16] Arsenic modulates posttranslational S-nitrosylation and translational proteome in keratinocytes. ScientificWorldJournal. 2014;2014:360153.
• [17] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [18] Synergistic effect of trichostatin A and 5-aza-2'-deoxycytidine on growth inhibition of pancreatic endocrine tumour cell lines: a proteomic study. Proteomics. 2009 Apr;9(7):1952-66. doi: 10.1002/pmic.200701089.
• [19] Dephosphorylation of ribosomal protein P0 in response to troglitazone-induced cytotoxicity. Toxicol Lett. 2006 Oct 25;166(3):189-99. doi: 10.1016/j.toxlet.2006.07.303. Epub 2006 Aug 8.
• [20] Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1839-44. doi: 10.1073/pnas.1424171112. Epub 2015 Jan 20.
• [21] RNA-binding proteins and heat-shock protein 90 are constituents of the cytoplasmic capping enzyme interactome. J Biol Chem. 2018 Oct 26;293(43):16596-16607. doi: 10.1074/jbc.RA118.004973. Epub 2018 Aug 30.
• [22] 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.
• [23] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [24] A proteomic analysis of acute leukemia cells treated with 9-hydroxyoctadecadienoic acid. Lipids Health Dis. 2016 Nov 10;15(1):192. doi: 10.1186/s12944-016-0359-4.