Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB41D5K)

• DOT Name: Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B)
• Synonyms: Cell cycle-related and expression-elevated protein in tumor
• Gene Name: RPRD1B
• Related Disease:
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Liver cancer
  Neoplasm
  Colorectal carcinoma
  Gastric cancer
  Stomach cancer
  Advanced cancer
• UniProt ID: RPR1B_HUMAN
• PDB ID: 4FLA; 4FU3; 4HFG; 4NAD; 4Q94; 4Q96
• Pfam ID: PF04818 ; PF16566
• Sequence:
  MSSFSESALEKKLSELSNSQQSVQTLSLWLIHHRKHAGPIVSVWHRELRKAKSNRKLTFL
  YLANDVIQNSKRKGPEFTREFESVLVDAFSHVAREADEGCKKPLERLLNIWQERSVYGGE
  FIQQLKLSMEDSKSPPPKATEEKKSLKRTFQQIQEEEDDDYPGSYSPQDPSAGPLLTEEL
  IKALQDLENAASGDATVRQKIASLPQEVQDVSLLEKITDKEAAERLSKTVDEACLLLAEY
  NGRLAAELEDRRQLARMLVEYTQNQKDVLSEKEKKLEEYKQKLARVTQVRKELKSHIQSL
  PDLSLLPNVTGGLAPLPSAGDLFSTD
• Function: Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD by RPAP2. Transcriptional regulator which enhances expression of CCND1. Promotes binding of RNA polymerase II to the CCDN1 promoter and to the termination region before the poly-A site but decreases its binding after the poly-A site. Prevents RNA polymerase II from reading through the 3' end termination site and may allow it to be recruited back to the promoter through promotion of the formation of a chromatin loop. Also enhances the transcription of a number of other cell cycle-related genes including CDK2, CDK4, CDK6 and cyclin-E but not CDKN1A, CDKN1B or cyclin-A. Promotes cell proliferation.
• Tissue Specificity: Preferentially expressed in a range of tumor tissues including colon, lung, liver, breast, prostate, stomach, uterine endometrium and cervical cancers with higher levels in tumors than in adjacent non-tumor tissue (at protein level).
• Reactome Pathway: RNA polymerase II transcribes snRNA genes (R-HSA-6807505)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Altered Expression	[3]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Liver cancer	DISDE4BI	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	moderate	Genetic Variation	[4]
Gastric cancer	DISXGOUK	moderate	Biomarker	[5]
Stomach cancer	DISKIJSX	moderate	Biomarker	[5]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[6]

4 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 Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[7]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[11]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[16]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Regulation of nuclear pre-mRNA domain-containing protein 1B (RPRD1B).	[17]

References

• [1] CREPT regulated by miR-138 promotes breast cancer progression.Biochem Biophys Res Commun. 2017 Nov 4;493(1):263-269. doi: 10.1016/j.bbrc.2017.09.033. Epub 2017 Sep 8.
• [2] MicroRNA-300 inhibits the growth of hepatocellular carcinoma cells by downregulating CREPT/Wnt/-catenin signaling.Oncol Lett. 2019 Oct;18(4):3743-3753. doi: 10.3892/ol.2019.10712. Epub 2019 Aug 5.
• [3] MicroRNA-383 acts as a tumor suppressor in colorectal cancer by modulating CREPT/RPRD1B expression.Mol Carcinog. 2018 Oct;57(10):1408-1420. doi: 10.1002/mc.22866. Epub 2018 Jul 3.
• [4] CREPT facilitates colorectal cancer growth through inducing Wnt/-catenin pathway by enhancing p300-mediated -catenin acetylation.Oncogene. 2018 Jun;37(26):3485-3500. doi: 10.1038/s41388-018-0161-z. Epub 2018 Mar 22.
• [5] Inhibition of CREPT restrains gastric cancer growth by regulation of cycle arrest, migration and apoptosis via ROS-regulated p53 pathway.Biochem Biophys Res Commun. 2018 Feb 19;496(4):1183-1190. doi: 10.1016/j.bbrc.2018.01.167. Epub 2018 Jan 31.
• [6] Clinical and Genome-Wide Analysis of Cisplatin-Induced Peripheral Neuropathy in Survivors of Adult-Onset Cancer.Clin Cancer Res. 2017 Oct 1;23(19):5757-5768. doi: 10.1158/1078-0432.CCR-16-3224. Epub 2017 Jun 13.
• [7] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray. Cancer Lett. 2004 Oct 8;214(1):19-33.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [14] Benzo[a]pyrene treatment leads to changes in nuclear protein expression and alternative splicing. Mutat Res. 2010 Apr 1;686(1-2):47-56. doi: 10.1016/j.mrfmmm.2010.01.015. Epub 2010 Jan 25.
• [15] 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.
• [16] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [17] 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.