Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT57AX7G)

• DOT Name: Small ribosomal subunit protein uS7m (MRPS7)
• Synonyms: 28S ribosomal protein S7, mitochondrial; MRP-S7; S7mt; bMRP-27a; bMRP27a
• Gene Name: MRPS7
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Kidney failure
  Obsolete syndromic sensorineural deafness due to combined oxidative phosphorylation defect
  Combined oxidative phosphorylation deficiency 34
• UniProt ID: RT07_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: PF00177
• Sequence:
  MAAPAVKVARGWSGLALGVRRAVLQLPGLTQVRWSRYSPEFKDPLIDKEYYRKPVEELTE
  EEKYVRELKKTQLIKAAPAGKTSSVFEDPVISKFTNMMMIGGNKVLARSLMIQTLEAVKR
  KQFEKYHAASAEEQATIERNPYTIFHQALKNCEPMIGLVPILKGGRFYQVPVPLPDRRRR
  FLAMKWMITECRDKKHQRTLMPEKLSHKLLEAFHNQGPVIKRKHDLHKMAEANRALAHYR
  WW
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[1]
Kidney failure	DISOVQ9P	Strong	Genetic Variation	[2]
Obsolete syndromic sensorineural deafness due to combined oxidative phosphorylation defect	DIS5PJ0W	Supportive	Autosomal recessive	[2]
Combined oxidative phosphorylation deficiency 34	DIS4H0ZZ	Limited	Unknown	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Small ribosomal subunit protein uS7m (MRPS7).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Small ribosomal subunit protein uS7m (MRPS7).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Small ribosomal subunit protein uS7m (MRPS7).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small ribosomal subunit protein uS7m (MRPS7).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein uS7m (MRPS7).	[7]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Small ribosomal subunit protein uS7m (MRPS7).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Small ribosomal subunit protein uS7m (MRPS7).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein uS7m (MRPS7).	[11]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Small ribosomal subunit protein uS7m (MRPS7).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Small ribosomal subunit protein uS7m (MRPS7).	[10]

References

• [1] An integrative approach to identify YB-1-interacting proteins required for cisplatin resistance in MCF7 and MDA-MB-231 breast cancer cells. Cancer Sci. 2011 Jul;102(7):1410-7. doi: 10.1111/j.1349-7006.2011.01948.x. Epub 2011 May 5.
• [2] Mutation in mitochondrial ribosomal protein S7 (MRPS7) causes congenital sensorineural deafness, progressive hepatic and renal failure and lactic acidemia. Hum Mol Genet. 2015 Apr 15;24(8):2297-307. doi: 10.1093/hmg/ddu747. Epub 2015 Jan 2.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [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] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [11] 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.
• [12] Comparative analysis of AhR-mediated TCDD-elicited gene expression in human liver adult stem cells. Toxicol Sci. 2009 Nov;112(1):229-44.