Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL868QS)

• DOT Name: Small ribosomal subunit protein bS18m (MRPS18C)
• Synonyms: 28S ribosomal protein S18-1, mitochondrial; MRP-S18-1; 28S ribosomal protein S18c, mitochondrial; MRP-S18-c; Mrps18-c; S18mt-c; Small ribosomal subunit protein bS18c
• Gene Name: MRPS18C
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: RT18C_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: PF01084
• Sequence:
  MAAVVAVCGGLGRKKLTHLVTAAVSLTHPGTHTVLWRRGCSQQVSSNEDLPISMENPYKE
  PLKKCILCGKHVDYKNVQLLSQFVSPFTGCIYGRHITGLCGKKQKEITKAIKRAQIMGFM
  PVTYKDPAYLKDPKVCNIRYRE
• 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
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Small ribosomal subunit protein bS18m (MRPS18C).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Small ribosomal subunit protein bS18m (MRPS18C).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Small ribosomal subunit protein bS18m (MRPS18C).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Small ribosomal subunit protein bS18m (MRPS18C).	[4]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Small ribosomal subunit protein bS18m (MRPS18C).	[5]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Small ribosomal subunit protein bS18m (MRPS18C).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Small ribosomal subunit protein bS18m (MRPS18C).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Small ribosomal subunit protein bS18m (MRPS18C).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Small ribosomal subunit protein bS18m (MRPS18C).	[10]

References

• [1] Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21.Oncotarget. 2016 Dec 6;7(49):80140-80163. doi: 10.18632/oncotarget.12818.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] 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] Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
• [6] Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.