Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3XXKDZ)

• DOT Name: Small ribosomal subunit protein bS16m (MRPS16)
• Synonyms: 28S ribosomal protein S16, mitochondrial; MRP-S16; S16mt
• Gene Name: MRPS16
• Related Disease:
  Combined oxidative phosphorylation defect type 2
  Mitochondrial disease
• UniProt ID: RT16_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: PF00886
• Sequence:
  MVHLTTLLCKAYRGGHLTIRLALGGCTNRPFYRIVAAHNKCPRDGRFVEQLGSYDPLPNS
  HGEKLVALNLDRIRHWIGCGAHLSKPMEKLLGLAGFFPLHPMMITNAERLRRKRAREVLL
  ASQKTDAEATDTEATET
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Combined oxidative phosphorylation defect type 2	DIS2FBXH	Supportive	Autosomal recessive	[1]
Mitochondrial disease	DISKAHA3	Limited	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Small ribosomal subunit protein bS16m (MRPS16).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small ribosomal subunit protein bS16m (MRPS16).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein bS16m (MRPS16).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Small ribosomal subunit protein bS16m (MRPS16).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Small ribosomal subunit protein bS16m (MRPS16).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Small ribosomal subunit protein bS16m (MRPS16).	[8]

References

• [1] Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation. Ann Neurol. 2004 Nov;56(5):734-8. doi: 10.1002/ana.20282.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] [Construction of subtracted cDNA library in human Jurkat T cell line induced by arsenic trioxide in vitro]. Zhonghua Yu Fang Yi Xue Za Zhi. 2003 Nov;37(6):403-7.
• [7] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [8] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.