Details of Drug Off-Target (DOT)

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

• DOT Name: BRI3-binding protein (BRI3BP)
• Synonyms: I3-binding protein; Cervical cancer 1 proto-oncogene-binding protein KG19; HCCRBP-1
• Gene Name: BRI3BP
• Related Disease:
  Advanced cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Liver cancer
  Breast cancer
  Neoplasm
  Gastric cancer
  Stomach cancer
• UniProt ID: BRI3B_HUMAN
• Pfam ID: PF14965
• Sequence:
  MGARASGGPLARAGLLLLLLLLLLLGLLAPGAQGARGRGGAEKNSYRRTVNTFSQSVSSL
  FGEDNVRAAQKFLARLTERFVLGVDMFVETLWKVWTELLDVLGLDVSNLSQYFSPASVSS
  SPARALLLVGVVLLAYWFLSLTLGFTFSVLHVVFGRFFWIVRVVLFSMSCVYILHKYEGE
  PENAVLPLCFVVAVYFMTGPMGFYWRSSPSGPSNPSNPSVEEKLEHLEKQVRLLNIRLNR
  VLESLDRSKDK
• Function: Involved in tumorigenesis and may function by stabilizing p53/TP53.
• Tissue Specificity: Most abundantly expressed in brain, liver and kidney . Overexpressed in leukemia and lymphoma cell lines, as well as in various carcinomas .

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
leukaemia	DISS7D1V	Strong	Altered Expression	[4]
Leukemia	DISNAKFL	Strong	Altered Expression	[4]
Liver cancer	DISDE4BI	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	moderate	Biomarker	[2]
Neoplasm	DISZKGEW	moderate	Altered Expression	[5]
Gastric cancer	DISXGOUK	Limited	Biomarker	[5]
Stomach cancer	DISKIJSX	Limited	Biomarker	[5]

11 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 BRI3-binding protein (BRI3BP).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of BRI3-binding protein (BRI3BP).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BRI3-binding protein (BRI3BP).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of BRI3-binding protein (BRI3BP).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of BRI3-binding protein (BRI3BP).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of BRI3-binding protein (BRI3BP).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of BRI3-binding protein (BRI3BP).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of BRI3-binding protein (BRI3BP).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of BRI3-binding protein (BRI3BP).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of BRI3-binding protein (BRI3BP).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of BRI3-binding protein (BRI3BP).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of BRI3-binding protein (BRI3BP).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of BRI3-binding protein (BRI3BP).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of BRI3-binding protein (BRI3BP).	[17]

References

• [1] Silencing of the HCCR2 gene induces apoptosis and suppresses the aggressive phenotype of hepatocellular carcinoma cells in culture.J Gastrointest Surg. 2011 Oct;15(10):1807-13. doi: 10.1007/s11605-011-1633-4. Epub 2011 Jul 28.
• [2] Interaction of HCCR-1 and Bax in breast cancer.J BUON. 2019 May-Jun;24(3):1027-1037.
• [3] Clinical implication of elevated human cervical cancer oncogene-1 expression in esophageal squamous cell carcinoma.J Histochem Cytochem. 2012 Jul;60(7):512-20. doi: 10.1369/0022155412444437. Epub 2012 Apr 17.
• [4] Identification and differential expression of novel human cervical cancer oncogene HCCR-2 in human cancers and its involvement in p53 stabilization.Oncogene. 2003 Jul 24;22(30):4679-89. doi: 10.1038/sj.onc.1206624.
• [5] HCCR-1 is a Novel Prognostic Indicator for Gastric Cancer and Promotes Cell Proliferation.J Cancer. 2019 Jun 9;10(15):3533-3542. doi: 10.7150/jca.22462. eCollection 2019.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] 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.
• [17] 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.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.