Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRBKF6R)

• DOT Name: Large ribosomal subunit protein bL19m (MRPL19)
• Synonyms: 39S ribosomal protein L15, mitochondrial; L15mt; MRP-L15; 39S ribosomal protein L19, mitochondrial; L19mt; MRP-L19
• Gene Name: MRPL19
• Related Disease:
  Neoplasm
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Endometrial carcinoma
  Melanoma
  Acute myelogenous leukaemia
• UniProt ID: RM19_HUMAN
• PDB ID: 3J7Y ; 3J9M ; 5OOL ; 5OOM ; 6I9R ; 6NU2 ; 6NU3 ; 6VLZ ; 6VMI ; 6ZM5 ; 6ZM6 ; 6ZS9 ; 6ZSA ; 6ZSB ; 6ZSC ; 6ZSD ; 6ZSE ; 6ZSG ; 7A5F ; 7A5G ; 7A5H ; 7A5I ; 7A5J ; 7A5K ; 7L08 ; 7L20 ; 7O9K ; 7O9M ; 7ODR ; 7ODS ; 7ODT ; 7OF0 ; 7OF2 ; 7OF3 ; 7OF4 ; 7OF5 ; 7OF6 ; 7OF7 ; 7OG4 ; 7OI6 ; 7OI7 ; 7OI8 ; 7OI9 ; 7OIA ; 7OIB ; 7OIC ; 7OID ; 7OIE ; 7PD3 ; 7PO4 ; 7QH6 ; 7QH7 ; 7QI4 ; 7QI5 ; 7QI6 ; 8ANY ; 8OIR ; 8OIS ; 8OIT
• Pfam ID: PF01245
• Sequence:
  MAACIAAGHWAAMGLGRSFQAARTLLPPPASIACRVHAGPVRQQSTGPSEPGAFQPPPKP
  VIVDKHRPVEPERRFLSPEFIPRRGRTDPLKFQIERKDMLERRKVLHIPEFYVGSILRVT
  TADPYASGKISQFLGICIQRSGRGLGATFILRNVIEGQGVEICFELYNPRVQEIQVVKLE
  KRLDDSLLYLRDALPEYSTFDVNMKPVVQEPNQKVPVNELKVKMKPKPWSKRWERPNFNI
  KGIRFDLCLTEQQMKEAQKWNQPWLEFDMMREYDTSKIEAAIWKEIEASKRS
• KEGG Pathway: Ribosome (hsa03010)
• 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[3]
Melanoma	DIS1RRCY	Strong	Altered Expression	[4]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large ribosomal subunit protein bL19m (MRPL19).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Large ribosomal subunit protein bL19m (MRPL19).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein bL19m (MRPL19).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Large ribosomal subunit protein bL19m (MRPL19).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Large ribosomal subunit protein bL19m (MRPL19).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Large ribosomal subunit protein bL19m (MRPL19).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Large ribosomal subunit protein bL19m (MRPL19).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Large ribosomal subunit protein bL19m (MRPL19).	[13]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Large ribosomal subunit protein bL19m (MRPL19).	[14]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Large ribosomal subunit protein bL19m (MRPL19).	[15]

References

• [1] Identification of endogenous control genes for normalisation of real-time quantitative PCR data in colorectal cancer.BMC Mol Biol. 2010 Feb 1;11:12. doi: 10.1186/1471-2199-11-12.
• [2] 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.
• [3] Validation of endogenous control reference genes for normalizing gene expression studies in endometrial carcinoma.Mol Hum Reprod. 2015 Sep;21(9):723-35. doi: 10.1093/molehr/gav033. Epub 2015 Jun 29.
• [4] Identification of robust reference genes for studies of gene expression in FFPE melanoma samples and melanoma cell lines.Melanoma Res. 2020 Feb;30(1):26-38. doi: 10.1097/CMR.0000000000000644.
• [5] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Comparison of quantitation methods in proteomics to define relevant toxicological information on AhR activation of HepG2 cells by BaP. Toxicology. 2021 Jan 30;448:152652. doi: 10.1016/j.tox.2020.152652. Epub 2020 Dec 2.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [15] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.