Details of Drug Off-Target (DOT)

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

• DOT Name: Active regulator of SIRT1 (RPS19BP1)
• Synonyms: 40S ribosomal protein S19-binding protein 1; RPS19-binding protein 1; S19BP
• Gene Name: RPS19BP1
• Related Disease: Advanced cancer
• UniProt ID: AROS_HUMAN
• PDB ID: 7MQA; 8BBK
• Pfam ID: PF15684
• Sequence:
  MSAALLRRGLELLAASEAPRDPPGQAKPRGAPVKRPRKTKAIQAQKLRNSAKGKVPKSAL
  DEYRKRECRDHLRVNLKFLTRTRSTVAESVSQQILRQNRGRKACDRPVAKTKKKKAEGTV
  FTEEDFQKFQQEYFGS
• Function: Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Acts as a chaperone that specifically mediates the integration of RPS19 in state post-A1. Direct regulator of SIRT1. Enhances SIRT1-mediated deacetylation of p53/TP53, thereby participating in inhibition of p53/TP53-mediated transcriptional activity.
• Tissue Specificity: Widely expressed (at protein level).
• Reactome Pathway: Regulation of HSF1-mediated heat shock response (R-HSA-3371453)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Active regulator of SIRT1 (RPS19BP1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Active regulator of SIRT1 (RPS19BP1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Active regulator of SIRT1 (RPS19BP1).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Active regulator of SIRT1 (RPS19BP1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Active regulator of SIRT1 (RPS19BP1).	[6]

References

• [1] Active regulator of SIRT1 is required for cancer cell survival but not for SIRT1 activity.Open Biol. 2013 Nov 20;3(11):130130. doi: 10.1098/rsob.130130.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.