Details of Drug Off-Target (DOT)

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

• DOT Name: Small ribosomal subunit protein mS29 (DAP3)
• Synonyms: 28S ribosomal protein S29, mitochondrial; MRP-S29; S29mt; Death-associated protein 3; DAP-3; Ionizing radiation resistance conferring protein
• Gene Name: DAP3
• Related Disease:
  Advanced cancer
  Bone osteosarcoma
  Breast cancer
  Breast neoplasm
  Burkitt lymphoma
  Gastric cancer
  Glioblastoma multiforme
  Narcolepsy
  Osteosarcoma
  Stomach cancer
  Thyroid tumor
  Breast carcinoma
  Inflammatory bowel disease
  Adult glioblastoma
  Asthma
  Glioma
  Neoplasm
• UniProt ID: RT29_HUMAN
• PDB ID: 3J9M ; 6NU2 ; 6NU3 ; 6RW4 ; 6RW5 ; 6VLZ ; 6VMI ; 6ZM5 ; 6ZM6 ; 6ZS9 ; 6ZSA ; 6ZSB ; 6ZSC ; 6ZSD ; 6ZSE ; 6ZSG ; 7A5F ; 7A5G ; 7A5I ; 7A5K ; 7L08 ; 7OG4 ; 7P2E ; 7PNX ; 7PNY ; 7PNZ ; 7PO0 ; 7PO1 ; 7PO2 ; 7PO3 ; 7QI4 ; 7QI5 ; 7QI6 ; 8ANY ; 8CSP ; 8CSQ ; 8CSR ; 8CSS ; 8CST ; 8CSU ; 8OIR ; 8OIS
• Pfam ID: PF10236
• Sequence:
  MMLKGITRLISRIHKLDPGRFLHMGTQARQSIAAHLDNQVPVESPRAISRTNENDPAKHG
  DQHEGQHYNISPQDLETVFPHGLPPRFVMQVKTFSEACLMVRKPALELLHYLKNTSFAYP
  AIRYLLYGEKGTGKTLSLCHVIHFCAKQDWLILHIPDAHLWVKNCRDLLQSSYNKQRFDQ
  PLEASTWLKNFKTTNERFLNQIKVQEKYVWNKRESTEKGSPLGEVVEQGITRVRNATDAV
  GIVLKELKRQSSLGMFHLLVAVDGINALWGRTTLKREDKSPIAPEELALVHNLRKMMKND
  WHGGAIVSALSQTGSLFKPRKAYLPQELLGKEGFDALDPFIPILVSNYNPKEFESCIQYY
  LENNWLQHEKAPTEEGKKELLFLSNANPSLLERHCAYL
• Function: Involved in mediating interferon-gamma-induced cell death.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway:
  Mitochondrial translation elongation (R-HSA-5389840)
  Mitochondrial translation termination (R-HSA-5419276)
  Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[4]
Gastric cancer	DISXGOUK	Strong	Biomarker	[5]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[6]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[5]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[8]
Inflammatory bowel disease	DISGN23E	moderate	Genetic Variation	[9]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[10]
Asthma	DISW9QNS	Limited	Biomarker	[11]
Glioma	DIS5RPEH	Limited	Altered Expression	[10]
Neoplasm	DISZKGEW	Limited	Altered Expression	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Small ribosomal subunit protein mS29 (DAP3).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Small ribosomal subunit protein mS29 (DAP3).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Small ribosomal subunit protein mS29 (DAP3).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein mS29 (DAP3).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Small ribosomal subunit protein mS29 (DAP3).	[17]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Small ribosomal subunit protein mS29 (DAP3).	[18]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Small ribosomal subunit protein mS29 (DAP3).	[19]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Small ribosomal subunit protein mS29 (DAP3).	[20]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Small ribosomal subunit protein mS29 (DAP3).	[21]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Small ribosomal subunit protein mS29 (DAP3).	[22]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Small ribosomal subunit protein mS29 (DAP3).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein mS29 (DAP3).	[26]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Small ribosomal subunit protein mS29 (DAP3).	[24]

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 affects the methylation of Small ribosomal subunit protein mS29 (DAP3).	[25]

References

• [1] Effects of the knockdown of death-associated protein 3 expression on cell adhesion, growth and migration in breast cancer cells.Oncol Rep. 2015 May;33(5):2575-82. doi: 10.3892/or.2015.3825. Epub 2015 Mar 2.
• [2] LKB1 is crucial for TRAIL-mediated apoptosis induction in osteosarcoma.Anticancer Res. 2007 Mar-Apr;27(2):761-8.
• [3] An integrative approach to identify YB-1-interacting proteins required for cisplatin resistance in MCF7 and MDA-MB-231 breast cancer cells. Cancer Sci. 2011 Jul;102(7):1410-7. doi: 10.1111/j.1349-7006.2011.01948.x. Epub 2011 May 5.
• [4] Tiling resolution array comparative genomic hybridization, expression and methylation analyses of dup(1q) in Burkitt lymphomas and pediatric high hyperdiploid acute lymphoblastic leukemias reveal clustered near-centromeric breakpoints and overexpression of genes in 1q22-32.3.Hum Mol Genet. 2007 Sep 15;16(18):2215-25. doi: 10.1093/hmg/ddm173. Epub 2007 Jul 5.
• [5] Depletion of death-associated protein-3 induces chemoresistance in gastric cancer cells through the -catenin/LGR5/Bcl-2 axis.J Investig Med. 2019 Jun;67(5):856-861. doi: 10.1136/jim-2018-000934. Epub 2019 Feb 20.
• [6] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [7] Death-associated protein 3 is overexpressed in human thyroid oncocytic tumours.Br J Cancer. 2009 Jul 7;101(1):132-8. doi: 10.1038/sj.bjc.6605111. Epub 2009 Jun 16.
• [8] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [9] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [10] Death-associated protein 3 (Dap-3) is overexpressed in invasive glioblastoma cells in vivo and in glioma cell lines with induced motility phenotype in vitro.Clin Cancer Res. 2001 Aug;7(8):2480-9.
• [11] Association between genetic variation in the gene for death-associated protein-3 (DAP3) and adult asthma.J Hum Genet. 2004;49(7):370-375. doi: 10.1007/s10038-004-0161-4. Epub 2004 Jun 4.
• [12] The mRNA expression of DAP3 in human breast cancer: correlation with clinicopathological parameters.Anticancer Res. 2012 Feb;32(2):671-4.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] 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.
• [15] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [16] 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.
• [17] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [18] Bortezomib induces caspase-dependent apoptosis in Hodgkin lymphoma cell lines and is associated with reduced c-FLIP expression: a gene expression profiling study with implications for potential combination therapies. Leuk Res. 2008 Feb;32(2):275-85. doi: 10.1016/j.leukres.2007.05.024. Epub 2007 Jul 19.
• [19] Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-alpha, CH11 and CYC202. Endocr Relat Cancer. 2007 Jun;14(2):305-15. doi: 10.1677/ERC-06-0003.
• [20] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [21] Plasmatic concentration of organochlorine lindane acts as metabolic disruptors in HepG2 liver cell line by inducing mitochondrial disorder. Toxicol Appl Pharmacol. 2013 Oct 15;272(2):325-34.
• [22] Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6. doi: 10.1016/j.bbrc.2003.12.146.
• [23] Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
• [24] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [25] 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.
• [26] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.