Details of Drug Off-Target (DOT)

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

• DOT Name: Large ribosomal subunit protein eL29 (RPL29)
• Synonyms: 60S ribosomal protein L29; Cell surface heparin-binding protein HIP
• Gene Name: RPL29
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Bipolar disorder
  Breast cancer
  Carcinoma
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Colorectal carcinoma
  Dementia
  Herpes simplex infection
  Liver cancer
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Neoplasm
  Obesity
  Osteoarthritis
  Osteoporosis
  Pancreatic cancer
  Pancreatitis
  Polyp
  Prostate cancer
  Prostate carcinoma
  Thyroid gland carcinoma
  Thyroid tumor
  Cryptorchidism
  Hyperglycemia
  Non-insulin dependent diabetes
  Type-1/2 diabetes
• UniProt ID: RL29_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5AJ0 ; 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 ; 8FL6 ; 8FL7 ; 8FL9 ; 8FLA ; 8FLB ; 8FLC ; 8FLD ; 8FLE ; 8FLF ; 8G5Y ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8IDT ; 8IDY ; 8IE3 ; 8INE ; 8INF ; 8INK ; 8IPD ; 8IPX ; 8IPY ; 8JDJ ; 8JDK ; 8JDL ; 8JDM
• Pfam ID: PF01779
• Sequence:
  MAKSKNHTTHNQSRKWHRNGIKKPRSQRYESLKGVDPKFLRNMRFAKKHNKKGLKKMQAN
  NAKAMSARAEAIKALVKPKEVKPKIPKGVSRKLDRLAYIAHPKLGKRARARIAKGLRLCR
  PKAKAKAKAKDQTKAQAAAPASVPAQAPKRTQAPTKASE
• 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

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Amyloidosis	DISHTAI2	Strong	Biomarker	[3]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[7]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Dementia	DISXL1WY	Strong	Biomarker	[9]
Herpes simplex infection	DISL1SAV	Strong	Genetic Variation	[10]
Liver cancer	DISDE4BI	Strong	Altered Expression	[11]
Lung cancer	DISCM4YA	Strong	Altered Expression	[12]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[12]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[13]
Osteoarthritis	DIS05URM	Strong	Biomarker	[14]
Osteoporosis	DISF2JE0	Strong	Biomarker	[14]
Pancreatic cancer	DISJC981	Strong	Biomarker	[15]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[16]
Polyp	DISRSLYF	Strong	Altered Expression	[17]
Prostate cancer	DISF190Y	Strong	Altered Expression	[12]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[12]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[6]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[6]
Cryptorchidism	DISYUD2P	Limited	Biomarker	[18]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[19]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[20]
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
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Large ribosomal subunit protein eL29 (RPL29).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein eL29 (RPL29).	[22]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Large ribosomal subunit protein eL29 (RPL29).	[21]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Large ribosomal subunit protein eL29 (RPL29).	[23]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Large ribosomal subunit protein eL29 (RPL29).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Large ribosomal subunit protein eL29 (RPL29).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Large ribosomal subunit protein eL29 (RPL29).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein eL29 (RPL29).	[28]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Large ribosomal subunit protein eL29 (RPL29).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Large ribosomal subunit protein eL29 (RPL29).	[27]

References

• [1] Identification of valid reference genes for gene expression studies of human stomach cancer by reverse transcription-qPCR.BMC Cancer. 2010 May 28;10:240. doi: 10.1186/1471-2407-10-240.
• [2] Apolipoprotein E 4 Specifically Modulates the Hippocampus Functional Connectivity Network in Patients With Amnestic Mild Cognitive Impairment.Front Aging Neurosci. 2018 Sep 27;10:289. doi: 10.3389/fnagi.2018.00289. eCollection 2018.
• [3] Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries.Kidney Int. 2020 Jan;97(1):143-155. doi: 10.1016/j.kint.2019.07.028. Epub 2019 Sep 5.
• [4] Common and distinct abnormal frontal-limbic system structural and functional patterns in patients with major depression and bipolar disorder.Neuroimage Clin. 2018 Jul 6;20:42-50. doi: 10.1016/j.nicl.2018.07.002. eCollection 2018.
• [5] Preliminary toxicity results using partial breast 3D-CRT with once daily hypo-fractionation and deep inspiratory breath hold.Radiat Oncol. 2018 Jul 27;13(1):135. doi: 10.1186/s13014-018-1079-x.
• [6] Overexpression of the HIP gene coding for a heparin/heparan sulfate-binding protein in human thyroid carcinomas.Cancer Res. 1998 Oct 15;58(20):4745-51.
• [7] Repression of HIP/RPL29 expression induces differentiation in colon cancer cells.J Cell Physiol. 2006 May;207(2):287-92. doi: 10.1002/jcp.20589.
• [8] The HIP gene encoding a heparin/heparan sulfate interacting protein is mutated in metastatic human colorectal cancer.Int J Mol Med. 2003 Apr;11(4):473-7.
• [9] Amyloid deposition and brain structure as long-term predictors of MCI, dementia, and mortality.Neurology. 2018 May 22;90(21):e1920-e1928. doi: 10.1212/WNL.0000000000005549. Epub 2018 Apr 25.
• [10] Construction and properties of a herpes simplex virus 2 dl5-29 vaccine candidate strain encoding an HSV-1 virion host shutoff protein.Vaccine. 2010 Mar 24;28(15):2754-62. doi: 10.1016/j.vaccine.2010.01.030. Epub 2010 Jan 29.
• [11] The human HIP gene, overexpressed in primary liver cancer encodes for a C-type carbohydrate binding protein with lactose binding activity.FEBS Lett. 1994 Jan 3;337(1):114-8. doi: 10.1016/0014-5793(94)80640-3.
• [12] Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors.BMC Cancer. 2004 Aug 4;4:43. doi: 10.1186/1471-2407-4-43.
• [13] PAP/HIP protein is an obesogenic factor.J Cell Physiol. 2014 Feb;229(2):225-31. doi: 10.1002/jcp.24438.
• [14] Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases.Aging (Albany NY). 2011 Jul;3(7):672-84. doi: 10.18632/aging.100355.
• [15] Silencing expression of ribosomal protein L26 and L29 by RNA interfering inhibits proliferation of human pancreatic cancer PANC-1 cells.Mol Cell Biochem. 2012 Nov;370(1-2):127-39. doi: 10.1007/s11010-012-1404-x. Epub 2012 Aug 7.
• [16] Structural organization and chromosomal localization of a human gene (HIP/PAP) encoding a C-type lectin overexpressed in primary liver cancer.Eur J Biochem. 1994 Aug 15;224(1):29-38. doi: 10.1111/j.1432-1033.1994.tb19991.x.
• [17] Heparin/heparan sulfate interacting protein gene expression is up-regulated in human colorectal carcinoma and correlated with differentiation status and metastasis.Cancer Res. 1999 Jun 15;59(12):2989-94.
• [18] Trisomy 14 mosaicism in a 5-year-old boy.Am J Med Genet. 1991 Jul 1;40(1):80-3. doi: 10.1002/ajmg.1320400116.
• [19] Diabetes due to a progressive defect in beta-cell mass in rats transgenic for human islet amyloid polypeptide (HIP Rat): a new model for type 2 diabetes.Diabetes. 2004 Jun;53(6):1509-16. doi: 10.2337/diabetes.53.6.1509.
• [20] Lower sarcoplasmic reticulum Ca(2+) threshold for triggering afterdepolarizations in diabetic rat hearts.Heart Rhythm. 2019 May;16(5):765-772. doi: 10.1016/j.hrthm.2018.11.001. Epub 2018 Nov 7.
• [21] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [22] 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.
• [23] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [26] 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.
• [27] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [28] 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.
• [29] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.