Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD5RXDI)

• DOT Name: Large ribosomal subunit protein mL42 (MRPL42)
• Synonyms: 39S ribosomal protein L31, mitochondrial; L31mt; MRP-L31; 39S ribosomal protein L42, mitochondrial; L42mt; MRP-L42
• Gene Name: MRPL42
• Related Disease: Glioma
• UniProt ID: RM42_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 ; 8OIT
• Pfam ID: PF10210
• Sequence:
  MAVAAVKWVMSKRTILKHLFPVQNGALYCVCHKSTYSPLPDDYNCNVELALTSDGRTIVC
  YHPSVDIPYEHTKPIPRPDPVHNNEETHDQVLKTRLEEKVEHLEEGPMIEQLSKMFFTTK
  HRWYPHGRYHRCRKNLNPPKDR
• 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

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Strong	Biomarker	[1]

7 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 Large ribosomal subunit protein mL42 (MRPL42).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Large ribosomal subunit protein mL42 (MRPL42).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large ribosomal subunit protein mL42 (MRPL42).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Large ribosomal subunit protein mL42 (MRPL42).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Large ribosomal subunit protein mL42 (MRPL42).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Large ribosomal subunit protein mL42 (MRPL42).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein mL42 (MRPL42).	[8]

References

• [1] Knockdown of MRPL42 suppresses glioma cell proliferation by inducing cell cycle arrest and apoptosis.Biosci Rep. 2018 Apr 27;38(2):BSR20171456. doi: 10.1042/BSR20171456. Print 2018 Apr 27.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] 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.
• [6] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] 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.