Details of Drug Off-Target (DOT)

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

• DOT Name: Ribosome production factor 2 homolog (RPF2)
• Synonyms: Brix domain-containing protein 1; Ribosome biogenesis protein RPF2 homolog
• Gene Name: RPF2
• Related Disease: Blindness
• UniProt ID: RPF2_HUMAN
• PDB ID: 8FL0; 8IR1; 8IR3
• Pfam ID: PF04427
• Sequence:
  MDTLDRVVKPKTKRAKRFLEKREPKLNENIKNAMLIKGGNANATVTKVLKDVYALKKPYG
  VLYKKKNITRPFEDQTSLEFFSKKSDCSLFMFGSHNKKRPNNLVIGRMYDYHVLDMIELG
  IENFVSLKDIKNSKCPEGTKPMLIFAGDDFDVTEDYRRLKSLLIDFFRGPTVSNIRLAGL
  EYVLHFTALNGKIYFRSYKLLLKKSGCRTPRIELEEMGPSLDLVLRRTHLASDDLYKLSM
  KMPKALKPKKKKNISHDTFGTTYGRIHMQKQDLSKLQTRKMKGLKKRPAERITEDHEKKS
  KRIKKN
• Function: Involved in ribosomal large subunit assembly. May regulate the localization of the 5S RNP/5S ribonucleoprotein particle to the nucleolus.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Blindness	DISTIM10	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ribosome production factor 2 homolog (RPF2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ribosome production factor 2 homolog (RPF2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribosome production factor 2 homolog (RPF2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ribosome production factor 2 homolog (RPF2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribosome production factor 2 homolog (RPF2).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ribosome production factor 2 homolog (RPF2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ribosome production factor 2 homolog (RPF2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribosome production factor 2 homolog (RPF2).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ribosome production factor 2 homolog (RPF2).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Ribosome production factor 2 homolog (RPF2).	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Ribosome production factor 2 homolog (RPF2).	[13]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Ribosome production factor 2 homolog (RPF2).	[14]

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 Ribosome production factor 2 homolog (RPF2).	[9]

References

• [1] A Drug-Tunable Gene Therapy for Broad-Spectrum Protection against Retinal Degeneration.Mol Ther. 2018 Oct 3;26(10):2407-2417. doi: 10.1016/j.ymthe.2018.07.016. Epub 2018 Jul 19.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] 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.
• [10] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [13] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [14] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.