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
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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]
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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]
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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.