Details of Drug Off-Target (DOT)

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

• DOT Name: Ribosomal RNA processing protein 1 homolog B (RRP1B)
• Synonyms: RRP1-like protein B
• Gene Name: RRP1B
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Neuroblastoma
  Coronary heart disease
  Neoplasm
• UniProt ID: RRP1B_HUMAN
• PDB ID: 7T0Y
• Pfam ID: PF05997
• Sequence:
  MAPAMQPAEIQFAQRLASSEKGIRDRAVKKLRQYISVKTQRETGGFSQEELLKIWKGLFY
  CMWVQDEPLLQEELANTIAQLVHAVNNSAAQHLFIQTFWQTMNREWKGIDRLRLDKYYML
  IRLVLRQSFEVLKRNGWEESRIKVFLDVLMKEVLCPESQSPNGVRFHFIDIYLDELSKVG
  GKELLADQNLKFIDPFCKIAAKTKDHTLVQTIARGVFEAIVDQSPFVPEETMEEQKTKVG
  DGDLSAEEIPENEVSLRRAVSKKKTALGKNHSRKDGLSDERGRDDCGTFEDTGPLLQFDY
  KAVADRLLEMTSRKNTPHFNRKRLSKLIKKFQDLSEGSSISQLSFAEDISADEDDQILSQ
  GKHKKKGNKLLEKTNLEKEKGSRVFCVEEEDSESSLQKRRRKKKKKHHLQPENPGPGGAA
  PSLEQNRGREPEASGLKALKARVAEPGAEATSSTGEESGSEHPPAVPMHNKRKRPRKKSP
  RAHREMLESAVLPPEDMSQSGPSGSHPQGPRGSPTGGAQLLKRKRKLGVVPVNGSGLSTP
  AWPPLQQEGPPTGPAEGANSHTTLPQRRRLQKKKAGPGSLELCGLPSQKTASLKKRKKMR
  VMSNLVEHNGVLESEAGQPQALGSSGTCSSLKKQKLRAESDFVKFDTPFLPKPLFFRRAK
  SSTATHPPGPAVQLNKTPSSSKKVTFGLNRNMTAEFKKTDKSILVSPTGPSRVAFDPEQK
  PLHGVLKTPTSSPASSPLVAKKPLTTTPRRRPRAMDFF
• Function: Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1. Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus. Involved in regulation of mRNA splicing. Inhibits SIPA1 GTPase activity. Involved in regulating expression of extracellular matrix genes. Associates with chromatin and may play a role in modulating chromatin structure ; (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[1]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[4]
Neoplasm	DISZKGEW	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[13]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[14]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Ribosomal RNA processing protein 1 homolog B (RRP1B).	[15]

References

• [1] Novel products of the HUD, HUC, NNP-1 and alpha-internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library.Int J Cancer. 2002 Aug 20;100(6):669-77. doi: 10.1002/ijc.10550.
• [2] The contribution of SIPA1 and RRP1B germline polymorphisms to breast cancer phenotype, lymph node status and survival in a group of Lithuanian young breast cancer patients.Biomarkers. 2016;21(4):363-70. doi: 10.3109/1354750X.2016.1141989. Epub 2016 Feb 22.
• [3] Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.PLoS Genet. 2007 Nov;3(11):e214. doi: 10.1371/journal.pgen.0030214. Epub 2007 Oct 16.
• [4] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [5] Potential lncRNA diagnostic biomarkers for early gastric cancer.Mol Med Rep. 2017 Dec;16(6):9545-9552. doi: 10.3892/mmr.2017.7770. Epub 2017 Oct 12.
• [6] 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.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [11] 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.
• [12] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [13] 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.
• [14] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.
• [15] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [16] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.