Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5ZZFJL)

• DOT Name: Transcription factor BTF3 (BTF3)
• Synonyms: Nascent polypeptide-associated complex subunit beta; NAC-beta; RNA polymerase B transcription factor 3
• Gene Name: BTF3
• Related Disease:
  Bone osteosarcoma
  Osteosarcoma
  Ataxia-telangiectasia
  Atypical teratoid/rhabdoid tumour
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Glioma
  Hypopharyngeal squamous cell carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Colon cancer
  Colon carcinoma
  Gastric cancer
  Stomach cancer
  Adenocarcinoma
  Advanced cancer
  Dental caries
  Glioblastoma multiforme
  Matthew-Wood syndrome
  Nasopharyngeal carcinoma
  Pancreatic cancer
  Pancreatic ductal carcinoma
• UniProt ID: BTF3_HUMAN
• PDB ID: 3LKX; 3MCB; 7QWQ; 7QWR
• Pfam ID: PF01849
• Sequence:
  MRRTGAPAQADSRGRGRARGGCPGGEATLSQPPPRGGTRGQEPQMKETIMNQEKLAKLQA
  QVRIGGKGTARRKKKVVHRTATADDKKLQFSLKKLGVNNISGIEEVNMFTNQGTVIHFNN
  PKVQASLAANTFTITGHAETKQLTEMLPSILNQLGADSLTSLRRLAEALPKQSVDGKAPL
  ATGEDDDDEVPDLVENFDEASKNEAN
• Function: When associated with NACA, prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. BTF3 is also a general transcription factor that can form a stable complex with RNA polymerase II. Required for the initiation of transcription.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Ataxia-telangiectasia	DISP3EVR	Strong	Altered Expression	[2]
Atypical teratoid/rhabdoid tumour	DIS1FA0D	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Biomarker	[6]
Hypopharyngeal squamous cell carcinoma	DISDDD65	Strong	Altered Expression	[7]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[10]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[10]
Colon cancer	DISVC52G	moderate	Biomarker	[9]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[9]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[11]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[11]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[12]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[7]
Dental caries	DISRBCMD	Limited	Altered Expression	[13]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[12]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[12]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[14]
Pancreatic cancer	DISJC981	Limited	Posttranslational Modification	[12]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[12]

13 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 Transcription factor BTF3 (BTF3).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transcription factor BTF3 (BTF3).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transcription factor BTF3 (BTF3).	[17]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transcription factor BTF3 (BTF3).	[18]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Transcription factor BTF3 (BTF3).	[19]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Transcription factor BTF3 (BTF3).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor BTF3 (BTF3).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor BTF3 (BTF3).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription factor BTF3 (BTF3).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor BTF3 (BTF3).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transcription factor BTF3 (BTF3).	[25]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Transcription factor BTF3 (BTF3).	[26]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Transcription factor BTF3 (BTF3).	[27]

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 decreases the phosphorylation of Transcription factor BTF3 (BTF3).	[23]

References

• [1] BTF3 Silencing Inhibits the Proliferation of Osteosarcoma Cells.J Cancer. 2019 Apr 21;10(8):1855-1861. doi: 10.7150/jca.28476. eCollection 2019.
• [2] Quantitative proteomic analysis of induced pluripotent stem cells derived from a human Huntington's disease patient.Biochem J. 2012 Sep 15;446(3):359-71. doi: 10.1042/BJ20111495.
• [3] The new Greiner FC-Mix tubes equal the old Terumo ones and are useful as glucose stabilizer after prolonged storage of samples.Biochem Med (Zagreb). 2017 Oct 15;27(3):030901. doi: 10.11613/BM.2017.030901. Epub 2017 Aug 28.
• [4] Inhibition of BTF3 sensitizes luminal breast cancer cells to PI3K inhibition through the transcriptional regulation of ER.Cancer Lett. 2019 Jan;440-441:54-63. doi: 10.1016/j.canlet.2018.09.030. Epub 2018 Oct 10.
• [5] Positive expression of basic transcription factor 3 predicts poor survival of colorectal cancer patients: possible mechanisms involved.Cell Death Dis. 2019 Jul 1;10(7):509. doi: 10.1038/s41419-019-1747-2.
• [6] A new potential anti-cancer beta-carboline derivative decreases the expression levels of key proteins involved in glioma aggressiveness: A proteomic investigation.Drug Dev Res. 2020 Feb;81(1):32-42. doi: 10.1002/ddr.21600. Epub 2019 Sep 9.
• [7] Upregulation of BTF3 affects the proliferation, apoptosis, and cell cycle regulation in hypopharyngeal squamous cell carcinoma.Biomed Pharmacother. 2019 Oct;118:109211. doi: 10.1016/j.biopha.2019.109211. Epub 2019 Aug 9.
• [8] Clinicopathological significance of BTF3 expression in colorectal cancer.Tumour Biol. 2013 Aug;34(4):2141-6. doi: 10.1007/s13277-013-0745-8. Epub 2013 Mar 27.
• [9] Basic transcription factor 3 expression silencing attenuates colon cancer cell proliferation and migration in vitro.Oncol Lett. 2019 Jan;17(1):113-118. doi: 10.3892/ol.2018.9613. Epub 2018 Oct 24.
• [10] BTF3 sustains cancer stem-like phenotype of prostate cancer via stabilization of BMI1.J Exp Clin Cancer Res. 2019 May 28;38(1):227. doi: 10.1186/s13046-019-1222-z.
• [11] Basic Transcription Factor 3 Is Required for Proliferation and Epithelial-Mesenchymal Transition via Regulation of FOXM1 and JAK2/STAT3 Signaling in Gastric Cancer.Oncol Res. 2017 Nov 2;25(9):1453-1462. doi: 10.3727/096504017X14886494526344. Epub 2017 Mar 8.
• [12] Basic transcription factor 3 (BTF3) regulates transcription of tumor-associated genes in pancreatic cancer cells.Cancer Biol Ther. 2007 Mar;6(3):367-76. doi: 10.4161/cbt.6.3.3704. Epub 2007 Mar 13.
• [13] Fine-mapping of 5q12.1-13.3 unveils new genetic contributors to caries.Caries Res. 2013;47(4):273-83. doi: 10.1159/000346278. Epub 2013 Jan 30.
• [14] Expression and clinical significance of basic transcription factor 3 in nasopharyngeal carcinoma.Oncol Lett. 2019 Jan;17(1):789-796. doi: 10.3892/ol.2018.9699. Epub 2018 Nov 14.
• [15] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [16] 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.
• [17] 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.
• [18] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [19] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [20] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [21] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [26] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [27] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.