Details of Drug Off-Target (DOT)

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

• DOT Name: Large ribosomal subunit protein bL17m (MRPL17)
• Synonyms: 39S ribosomal protein L17, mitochondrial; L17mt; MRP-L17; LYST-interacting protein 2
• Gene Name: MRPL17
• Related Disease:
  Lung cancer
  Lung carcinoma
  Rheumatoid arthritis
• UniProt ID: RM17_HUMAN
• PDB ID: 2CQM ; 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 ; 8OIT
• Pfam ID: PF01196
• Sequence:
  MRLSVAAAISHGRVFRRMGLGPESRIHLLRNLLTGLVRHERIEAPWARVDEMRGYAEKLI
  DYGKLGDTNERAMRMADFWLTEKDLIPKLFQVLAPRYKDQTGGYTRMLQIPNRSLDRAKM
  AVIEYKGNCLPPLPLPRRDSHLTLLNQLLQGLRQDLRQSQEASNHSSHTAQTPGI
• Tissue Specificity: Detected in adrenal gland, mammary gland and adipose tissue.
• 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

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Large ribosomal subunit protein bL17m (MRPL17).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large ribosomal subunit protein bL17m (MRPL17).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Large ribosomal subunit protein bL17m (MRPL17).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein bL17m (MRPL17).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Large ribosomal subunit protein bL17m (MRPL17).	[7]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Large ribosomal subunit protein bL17m (MRPL17).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Large ribosomal subunit protein bL17m (MRPL17).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Large ribosomal subunit protein bL17m (MRPL17).	[10]

References

• [1] Screening of key genes and prediction of therapeutic agents in Arsenic-induced lung carcinoma.Cancer Biomark. 2019;25(4):351-360. doi: 10.3233/CBM-182333.
• [2] High levels of the proNGF peptides LIP1 and LIP2 in the serum and synovial fluid of rheumatoid arthritis patients: evidence for two new cytokines.J Neuroimmunol. 2008 Feb;194(1-2):143-6. doi: 10.1016/j.jneuroim.2007.11.002. Epub 2007 Dec 27.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.