Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFKNTD6)

• DOT Name: Large ribosomal subunit protein eL13 (RPL13)
• Synonyms: 60S ribosomal protein L13; Breast basic conserved protein 1
• Gene Name: RPL13
• Related Disease:
  Alzheimer disease
  Bone development disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
  Spondyloepimetaphyseal dysplasia
  Spondyloepimetaphyseal dysplasia, Isidor-Toutain type
  High blood pressure
  Spondyloepiphyseal dysplasia
  Diamond-Blackfan anemia
  Neoplasm
• UniProt ID: RL13_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 ; 8FL2 ; 8FL3 ; 8FL4 ; 8FL6 ; 8FL7 ; 8FL9 ; 8FLA ; 8FLB ; 8FLC ; 8FLD ; 8FLE ; 8FLF ; 8G5Y ; 8G5Z ; 8G60 ; 8G61 ; 8GLP ; 8IDT ; 8IDY ; 8IE3 ; 8INE ; 8INF ; 8INK ; 8IPD ; 8IPX ; 8IPY ; 8IR1 ; 8IR3 ; 8JDJ ; 8JDK ; 8JDL ; 8JDM
• Pfam ID: PF01294
• Sequence:
  MAPSRNGMVLKPHFHKDWQRRVATWFNQPARKIRRRKARQAKARRIAPRPASGPIRPIVR
  CPTVRYHTKVRAGRGFSLEELRVAGIHKKVARTIGISVDPRRRNKSTESLQANVQRLKEY
  RSKLILFPRKPSAPKKGDSSAEELKLATQLTGPVMPVRNVYKKEKARVITEEEKNFKAFA
  SLRMARANARLFGIRAKRAKEAAEQDVEKKK
• Function: Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (Probable). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (Probable). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (Probable). As part of the LSU, it is probably required for its formation and the maturation of rRNAs. Plays a role in bone development.
• Tissue Specificity: Higher levels of expression in benign breast lesions than in carcinomas.
• 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

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Bone development disease	DISVKAZS	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[4]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[4]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[6]
Spondyloepimetaphyseal dysplasia	DISO4L5A	Strong	Genetic Variation	[2]
Spondyloepimetaphyseal dysplasia, Isidor-Toutain type	DISJ0HYK	Strong	Autosomal dominant	[2]
High blood pressure	DISY2OHH	moderate	Biomarker	[7]
Spondyloepiphyseal dysplasia	DIS1JG9A	Moderate	Autosomal dominant	[2]
Diamond-Blackfan anemia	DISI2SNW	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Large ribosomal subunit protein eL13 (RPL13).	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of Large ribosomal subunit protein eL13 (RPL13).	[16]

12 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 eL13 (RPL13).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Large ribosomal subunit protein eL13 (RPL13).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Large ribosomal subunit protein eL13 (RPL13).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein eL13 (RPL13).	[13]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Large ribosomal subunit protein eL13 (RPL13).	[14]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Large ribosomal subunit protein eL13 (RPL13).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Large ribosomal subunit protein eL13 (RPL13).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein eL13 (RPL13).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Large ribosomal subunit protein eL13 (RPL13).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Large ribosomal subunit protein eL13 (RPL13).	[19]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Large ribosomal subunit protein eL13 (RPL13).	[20]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Large ribosomal subunit protein eL13 (RPL13).	[21]

References

• [1] Housekeepers for accurate transcript expression analysis in Alzheimer's disease autopsy brain tissue.Alzheimers Dement. 2010 Nov;6(6):465-74. doi: 10.1016/j.jalz.2009.11.002.
• [2] RPL13 Variants Cause Spondyloepimetaphyseal Dysplasia with Severe Short Stature. Am J Hum Genet. 2019 Nov 7;105(5):1040-1047. doi: 10.1016/j.ajhg.2019.09.024. Epub 2019 Oct 17.
• [3] Exclusion of BBC1 and CMAR as candidate breast tumour-suppressor genes.Br J Cancer. 1997;76(12):1550-3. doi: 10.1038/bjc.1997.594.
• [4] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [5] Differentially expressed genes in hormone refractory prostate cancer: association with chromosomal regions involved with genetic aberrations.Am J Pathol. 1999 May;154(5):1335-43. doi: 10.1016/S0002-9440(10)65387-4.
• [6] Alterations in oligodendrocyte proteins, calcium homeostasis and new potential markers in schizophrenia anterior temporal lobe are revealed by shotgun proteome analysis.J Neural Transm (Vienna). 2009 Mar;116(3):275-89. doi: 10.1007/s00702-008-0156-y. Epub 2008 Nov 26.
• [7] Identification of reliable reference genes for quantitative real-time PCR in lung and heart of pulmonary hypertensive chickens.Poult Sci. 2018 Nov 1;97(11):4048-4056. doi: 10.3382/ps/pey258.
• [8] Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia. Br J Haematol. 2015 Mar;168(6):854-64. doi: 10.1111/bjh.13229. Epub 2014 Nov 25.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [10] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [11] 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.
• [12] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [16] 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.
• [17] 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.
• [18] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [21] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.