Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1LYV85)

• DOT Name: Large ribosomal subunit protein eL42 (RPL36A)
• Synonyms: 60S ribosomal protein L36a; 60S ribosomal protein L44; Cell growth-inhibiting gene 15 protein; Cell migration-inducing gene 6 protein
• Gene Name: RPL36A
• Related Disease:
  Glioblastoma multiforme
  Adenocarcinoma
  Adult glioblastoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Diabetic kidney disease
  Endometrial carcinoma
  Endometrium adenocarcinoma
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung neoplasm
  Neoplasm
  Polycystic ovarian syndrome
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Lung carcinoma
  Non-small-cell lung cancer
  Endometrial cancer
  Hyperglycemia
  Melanoma
  Metastatic malignant neoplasm
  Type-1/2 diabetes
• UniProt ID: RL36A_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5AJ0 ; 5LKS ; 5T2C ; 6IP5 ; 6IP6 ; 6IP8 ; 6LQM ; 6LSR ; 6LSS ; 6LU8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6XA1 ; 6Y0G ; 6Y2L ; 6Y57 ; 6Y6X ; 6Z6M ; 6Z6N ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 7BHP ; 7F5S ; 7OW7 ; 8A3D ; 8IDT ; 8IDY ; 8INE ; 8INF ; 8JDJ ; 8JDK ; 8JDL ; 8JDM
• Pfam ID: PF00935
• Sequence:
  MVNVPKTRRTFCKKCGKHQPHKVTQYKKGKDSLYAQGKRRYDRKQSGYGGQTKPIFRKKA
  KTTKKIVLRLECVEPNCRSKRMLAIKRCKHFELGGDKKRKGQVIQF
• 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

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[6]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[7]
Endometrium adenocarcinoma	DISY6744	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[9]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[10]
Lung cancer	DISCM4YA	Strong	Biomarker	[11]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[13]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[14]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[14]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[14]
Lung carcinoma	DISTR26C	moderate	Biomarker	[11]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Altered Expression	[15]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[7]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[16]
Melanoma	DIS1RRCY	Limited	Altered Expression	[17]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[18]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[19]

9 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 eL42 (RPL36A).	[20]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Large ribosomal subunit protein eL42 (RPL36A).	[21]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Large ribosomal subunit protein eL42 (RPL36A).	[22]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Large ribosomal subunit protein eL42 (RPL36A).	[23]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Large ribosomal subunit protein eL42 (RPL36A).	[24]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Large ribosomal subunit protein eL42 (RPL36A).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Large ribosomal subunit protein eL42 (RPL36A).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein eL42 (RPL36A).	[27]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Large ribosomal subunit protein eL42 (RPL36A).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Large ribosomal subunit protein eL42 (RPL36A).	[26]

References

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• [2] Mig-6 deficiency cooperates with oncogenic Kras to promote mouse lung tumorigenesis.Lung Cancer. 2017 Oct;112:47-56. doi: 10.1016/j.lungcan.2017.08.001. Epub 2017 Aug 5.
• [3] microRNA-148a is a prognostic oncomiR that targets MIG6 and BIM to regulate EGFR and apoptosis in glioblastoma.Cancer Res. 2014 Mar 1;74(5):1541-53. doi: 10.1158/0008-5472.CAN-13-1449. Epub 2014 Jan 14.
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• [5] Tocotrienol-treated MCF-7 human breast cancer cells show down-regulation of API5 and up-regulation of MIG6 genes.Cancer Genomics Proteomics. 2011 Jan-Feb;8(1):19-31.
• [6] Gene 33/Mig-6, a transcriptionally inducible adapter protein that binds GTP-Cdc42 and activates SAPK/JNK. A potential marker transcript for chronic pathologic conditions, such as diabetic nephropathy. Possible role in the response to persistent stress.J Biol Chem. 2000 Jun 9;275(23):17838-47. doi: 10.1074/jbc.M909735199.
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• [8] Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease.Proc Natl Acad Sci U S A. 2009 May 26;106(21):8677-82. doi: 10.1073/pnas.0903632106. Epub 2009 May 13.
• [9] MicroRNA-374a Promotes Hepatocellular Carcinoma Cell Proliferation by Targeting Mitogen-Inducible Gene 6 (MIG-6).Oncol Res. 2018 May 7;26(4):557-563. doi: 10.3727/096504017X15000784459799. Epub 2017 Jul 21.
• [10] Phosphorylation of Mig6 negatively regulates the ubiquitination and degradation of EGFR mutants in lung adenocarcinoma cell lines.Cell Signal. 2018 Mar;43:21-31. doi: 10.1016/j.cellsig.2017.11.006. Epub 2017 Dec 2.
• [11] Conversion of MIG6 peptide from the nonbinder to binder of lung cancer-related EGFR by phosphorylation and cyclization.Artif Cells Nanomed Biotechnol. 2017 Aug;45(5):1023-1028. doi: 10.1080/21691401.2016.1200058. Epub 2016 Jun 25.
• [12] A calcium-dependent phospholipase A2 (cPLA2) expression is regulated by MIG-6 during endometrial tumorigenesis.Biochem Biophys Res Commun. 2019 Mar 26;511(1):129-134. doi: 10.1016/j.bbrc.2019.02.034. Epub 2019 Feb 14.
• [13] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [14] Mitogen-inducible gene-6 is a multifunctional adaptor protein with tumor suppressor-like activity in papillary thyroid cancer.J Clin Endocrinol Metab. 2011 Mar;96(3):E554-65. doi: 10.1210/jc.2010-1800. Epub 2010 Dec 29.
• [15] Lung cancer stem cells and their aggressive progeny, controlled by EGFR/MIG6 inverse expression, dictate a novel NSCLC treatment approach.Oncotarget. 2019 Apr 2;10(26):2546-2560. doi: 10.18632/oncotarget.26817. eCollection 2019 Apr 2.
• [16] Role of Mig-6 in hepatic glucose metabolism.J Diabetes. 2016 Jan;8(1):86-97. doi: 10.1111/1753-0407.12261. Epub 2015 Mar 24.
• [17] MIG6 Is MEK Regulated and Affects EGF-Induced Migration in Mutant NRAS Melanoma.J Invest Dermatol. 2016 Feb;136(2):453-463. doi: 10.1016/j.jid.2015.11.012. Epub 2015 Nov 20.
• [18] Mitogen Inducible Gene-6 Is a Prognostic Marker for Patients with Colorectal Liver Metastases.Transl Oncol. 2019 Mar;12(3):550-560. doi: 10.1016/j.tranon.2018.12.007. Epub 2019 Jan 9.
• [19] Mig6 haploinsufficiency protects mice against streptozotocin-induced diabetes.Diabetologia. 2014 Oct;57(10):2066-75. doi: 10.1007/s00125-014-3311-z. Epub 2014 Jul 4.
• [20] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [21] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [22] 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.
• [23] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [24] 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.
• [25] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [26] 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.
• [27] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [28] 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.