Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT3TKPI)

• DOT Name: Protein BTG4 (BTG4)
• Synonyms: BTG family member 4; Protein PC3b
• Gene Name: BTG4
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Gastric cancer
  Neoplasm
  Oocyte maturation defect 8
  Small lymphocytic lymphoma
  Stomach cancer
  Female infertility
• UniProt ID: BTG4_HUMAN
• Pfam ID: PF07742
• Sequence:
  MRDEIATTVFFVTRLVKKHDKLSKQQIEDFAEKLMTILFETYRSHWHSDCPSKGQAFRCI
  RINNNQNKDPILERACVESNVDFSHLGLPKEMTIWVDPFEVCCRYGEKNHPFTVASFKGR
  WEEWELYQQISYAVSRASSDVSSGTSCDEESCSKEPRVIPKVSNPKSIYQVENLKQPFQS
  WLQIPRKKNVVDGRVGLLGNTYHGSQKHPKCYRPAMHRLDRIL
• Function: Adapter protein that bridges CNOT7, a catalytic subunit of the CCR4-NOT complex, to EIF4E. Facilitates maternal mRNAs decay during the maturation of oocytes and in the fertilized egg, and is required for the maternal-zygotic transition (MZT), zygotic cleavage and initiation of embryonic development.
• Tissue Specificity: Expressed in oocytes after germinal vesicle breakdown . Expressed in testis and in olfactory epithelium.
• KEGG Pathway: R. degradation (hsa03018)
• Reactome Pathway: M-decay (R-HSA-9820841)

Molecular Interaction Atlas (MIA) of This DOT

10 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]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[2]
Colorectal neoplasm	DISR1UCN	Strong	Posttranslational Modification	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Oocyte maturation defect 8	DIS22ZRT	Strong	Autosomal recessive	[5]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[6]
Stomach cancer	DISKIJSX	Strong	Biomarker	[4]
Female infertility	DIS9GNYZ	Moderate	Autosomal recessive	[5]

4 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 Protein BTG4 (BTG4).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Protein BTG4 (BTG4).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein BTG4 (BTG4).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein BTG4 (BTG4).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein BTG4 (BTG4).	[10]

References

• [1] Expression and prognosis analyses of the Tob/BTG antiproliferative (APRO) protein family in human cancers.PLoS One. 2017 Sep 18;12(9):e0184902. doi: 10.1371/journal.pone.0184902. eCollection 2017.
• [2] Novel candidate colorectal cancer biomarkers identified by methylation microarray-based scanning.Endocr Relat Cancer. 2011 Jul 4;18(4):465-78. doi: 10.1530/ERC-11-0083. Print 2011 Aug.
• [3] Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer.Cancer Res. 2008 Jun 1;68(11):4123-32. doi: 10.1158/0008-5472.CAN-08-0325.
• [4] Frequent promoter hypermethylation and transcriptional downregulation of BTG4 gene in gastric cancer.Biochem Biophys Res Commun. 2009 Sep 11;387(1):132-8. doi: 10.1016/j.bbrc.2009.06.140. Epub 2009 Jul 1.
• [5] Homozygous Mutations in BTG4 Cause Zygotic Cleavage Failure and Female Infertility. Am J Hum Genet. 2020 Jul 2;107(1):24-33. doi: 10.1016/j.ajhg.2020.05.010. Epub 2020 Jun 4.
• [6] Methylation markers identify high risk patients in IGHV mutated chronic lymphocytic leukemia.Epigenetics. 2011 Mar;6(3):300-6. doi: 10.4161/epi.6.3.14038. Epub 2011 Mar 1.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [10] 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.