Details of Drug Off-Target (DOT)

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

• DOT Name: E3 ubiquitin-protein ligase RNF25 (RNF25)
• Synonyms: EC 2.3.2.27; RING finger protein 25; RING finger protein AO7
• Gene Name: RNF25
• Related Disease:
  Neoplasm
  Non-small-cell lung cancer
• UniProt ID: RNF25_HUMAN
• PDB ID: 2DAY; 2DMF; 5D1K; 5D1L; 5D1M
• EC Number: 2.3.2.27
• Pfam ID: PF05773 ; PF13639
• Sequence:
  MAASASAAAGEEDWVLPSEVEVLESIYLDELQVIKGNGRTSPWEIYITLHPATAEDQDSQ
  YVCFTLVLQVPAEYPHEVPQISIRNPRGLSDEQIHTILQVLGHVAKAGLGTAMLYELIEK
  GKEILTDNNIPHGQCVICLYGFQEKEAFTKTPCYHYFHCHCLARYIQHMEQELKAQGQEQ
  EQERQHATTKQKAVGVQCPVCREPLVYDLASLKAAPEPQQPMELYQPSAESLRQQEERKR
  LYQRQQERGGIIDLEAERNRYFISLQQPPAPAEPESAVDVSKGSQPPSTLAAELSTSPAV
  QSTLPPPLPVATQHICEKIPGTRSNQQRLGETQKAMLDPPKPSRGPWRQPERRHPKGGEC
  HAPKGTRDTQELPPPEGPLKEPMDLKPEPHSQGVEGPPQEKGPGSWQGPPPRRTRDCVRW
  ERSKGRTPGSSYPRLPRGQGAYRPGTRRESLGLESKDGS
• Function: E3 ubiquitin-protein ligase that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes. Catalyzes ubiquitination of RPS27A in response to ribosome collisions, promoting activation of RNF14. RNF25 catalyzes ubiquitination of other ribosomal proteins on stalled ribosomes, such as RPL0, RPL1, RPL12, RPS13 and RPS17. Also involved in ubiquitination and degradation of stalled ETF1/eRF1. Independently of its function in the response to stalled ribosomes, mediates ubiquitination and subsequent proteasomal degradation of NKD2. May also stimulate transcription mediated by NF-kappa-B via its interaction with RELA/p65.
• Reactome Pathway: Antigen processing (R-HSA-983168)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of E3 ubiquitin-protein ligase RNF25 (RNF25).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of E3 ubiquitin-protein ligase RNF25 (RNF25).	[4]
Marinol	DM70IK5	Approved	Marinol decreases the expression of E3 ubiquitin-protein ligase RNF25 (RNF25).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of E3 ubiquitin-protein ligase RNF25 (RNF25).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of E3 ubiquitin-protein ligase RNF25 (RNF25).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of E3 ubiquitin-protein ligase RNF25 (RNF25).	[7]

References

• [1] Combined Proteomics and Transcriptomics Identifies Carboxypeptidase B1 and Nuclear Factor B (NF-B) Associated Proteins as Putative Biomarkers of Metastasis in Low Grade Breast Cancer.Mol Cell Proteomics. 2015 Jul;14(7):1814-30. doi: 10.1074/mcp.M114.041335. Epub 2015 Apr 22.
• [2] RNF25 promotes gefitinib resistance in EGFR-mutant NSCLC cells by inducing NF-B-mediated ERK reactivation.Cell Death Dis. 2018 May 22;9(6):587. doi: 10.1038/s41419-018-0651-5.
• [3] 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.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] 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.
• [6] 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.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.