Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7LQ36N)

• DOT Name: Mitochondrial assembly of ribosomal large subunit protein 1 (MALSU1)
• Gene Name: MALSU1
• UniProt ID: MASU1_HUMAN
• PDB ID: 5OOL; 5OOM; 7A5H; 7A5J; 7O9K; 7O9M; 7ODR; 7ODS; 7ODT; 7OF0; 7OF2; 7OF3; 7OF5; 7OF7; 7OI6; 7OI7; 7OI8; 7OI9; 7OIC; 7OID; 7OIE; 7PD3; 7PO4; 7QH6; 7QH7
• Pfam ID: PF02410
• Sequence:
  MGPGGRVARLLAPLMWRRAVSSVAGSAVGAEPGLRLLAVQRLPVGAAFCRACQTPNFVRG
  LHSEPGLEERAEGTVNEGRPESDAADHTGPKFDIDMMVSLLRQENARDICVIQVPPEMRY
  TDYFVIVSGTSTRHLHAMAFYVVKMYKHLKCKRDPHVKIEGKDTDDWLCVDFGSMVIHLM
  LPETREIYELEKLWTLRSYDDQLAQIAPETVPEDFILGIEDDTSSVTPVELKCE
• Function: Required for normal mitochondrial ribosome function and mitochondrial translation. May play a role in ribosome biogenesis by preventing premature association of the 28S and 39S ribosomal subunits (Probable). Interacts with mitochondrial ribosomal protein uL14m (MRPL14), probably blocking formation of intersubunit bridge B8, preventing association of the 28S and 39S ribosomal subunits (Probable). Addition to isolated mitochondrial ribosomal subunits partially inhibits translation, probably by interfering with the association of the 28S and 39S ribosomal subunits and the formation of functional ribosomes (Probable). May also participate in the assembly and/or regulation of the stability of the large subunit of the mitochondrial ribosome. May function as a ribosomal silencing factor (Probable).

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Mitochondrial assembly of ribosomal large subunit protein 1 (MALSU1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial assembly of ribosomal large subunit protein 1 (MALSU1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial assembly of ribosomal large subunit protein 1 (MALSU1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mitochondrial assembly of ribosomal large subunit protein 1 (MALSU1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial assembly of ribosomal large subunit protein 1 (MALSU1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mitochondrial assembly of ribosomal large subunit protein 1 (MALSU1).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol affects the expression of Mitochondrial assembly of ribosomal large subunit protein 1 (MALSU1).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Mitochondrial assembly of ribosomal large subunit protein 1 (MALSU1).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.