Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHTOLE0)

• DOT Name: Small ribosomal subunit protein mS39 (PTCD3)
• Synonyms: 28S ribosomal protein S39, mitochondrial; MRP-S39; Pentatricopeptide repeat domain-containing protein 3, mitochondrial; Transformation-related gene 15 protein; TRG-15
• Gene Name: PTCD3
• Related Disease:
  B-cell neoplasm
  Combined oxidative phosphorylation deficiency 51
  Prostate cancer
  Prostate carcinoma
  Leigh syndrome
• UniProt ID: PTCD3_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: PF13041 ; PF13812
• Sequence:
  MAVVSAVRWLGLRSRLGQPLTGRRAGLCEQARSCRFYSGSATLSKVEGTDVTGIEEVVIP
  KKKTWDKVAVLQALASTVNRDTTAVPYVFQDDPYLMPASSLESRSFLLAKKSGENVAKFI
  INSYPKYFQKDIAEPHIPCLMPEYFEPQIKDISEAALKERIELRKVKASVDMFDQLLQAG
  TTVSLETTNSLLDLLCYYGDQEPSTDYHFQQTGQSEALEEENDETSRRKAGHQFGVTWRA
  KNNAERIFSLMPEKNEHSYCTMIRGMVKHRAYEQALNLYTELLNNRLHADVYTFNALIEA
  TVCAINEKFEEKWSKILELLRHMVAQKVKPNLQTFNTILKCLRRFHVFARSPALQVLREM
  KAIGIEPSLATYHHIIRLFDQPGDPLKRSSFIIYDIMNELMGKRFSPKDPDDDKFFQSAM
  SICSSLRDLELAYQVHGLLKTGDNWKFIGPDQHRNFYYSKFFDLICLMEQIDVTLKWYED
  LIPSAYFPHSQTMIHLLQALDVANRLEVIPKIWKDSKEYGHTFRSDLREEILMLMARDKH
  PPELQVAFADCAADIKSAYESQPIRQTAQDWPATSLNCIAILFLRAGRTQEAWKMLGLFR
  KHNKIPRSELLNELMDSAKVSNSPSQAIEVVELASAFSLPICEGLTQRVMSDFAINQEQK
  EALSNLTALTSDSDTDSSSDSDSDTSEGK
• Function: Mitochondrial RNA-binding protein that has a role in mitochondrial translation.
• Tissue Specificity: Abundant in testes, skeletal muscle and heart tissue.
• 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

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Strong	Biomarker	[1]
Combined oxidative phosphorylation deficiency 51	DIS4P2YC	Strong	Autosomal recessive	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[3]
Leigh syndrome	DISWQU45	Limited	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Small ribosomal subunit protein mS39 (PTCD3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Small ribosomal subunit protein mS39 (PTCD3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Small ribosomal subunit protein mS39 (PTCD3).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small ribosomal subunit protein mS39 (PTCD3).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein mS39 (PTCD3).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Small ribosomal subunit protein mS39 (PTCD3).	[10]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Small ribosomal subunit protein mS39 (PTCD3).	[11]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Small ribosomal subunit protein mS39 (PTCD3).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Small ribosomal subunit protein mS39 (PTCD3).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein mS39 (PTCD3).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Small ribosomal subunit protein mS39 (PTCD3).	[14]

References

• [1] The mitochondrial translation machinery as a therapeutic target in Myc-driven lymphomas.Oncotarget. 2016 Nov 8;7(45):72415-72430. doi: 10.18632/oncotarget.11719.
• [2] Mitochondrial ribosomal protein PTCD3 mutations cause oxidative phosphorylation defects with Leigh syndrome. Neurogenetics. 2019 Mar;20(1):9-25. doi: 10.1007/s10048-018-0561-9. Epub 2019 Jan 3.
• [3] Elevated expression of PTCD3 correlates with tumor progression and predicts poor prognosis in patients with prostate cancer.Mol Med Rep. 2018 Oct;18(4):3914-3922. doi: 10.3892/mmr.2018.9402. Epub 2018 Aug 20.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] 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.
• [11] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.