Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAH5NSO)

• DOT Name: Transcription initiation factor IIB (GTF2B)
• Synonyms: EC 2.3.1.48; General transcription factor TFIIB; S300-II
• Gene Name: GTF2B
• Related Disease:
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Non-small-cell lung cancer
  Osteoporosis
  Neoplasm
• UniProt ID: TF2B_HUMAN
• PDB ID: 1C9B ; 1DL6 ; 1RLY ; 1RO4 ; 1TFB ; 1VOL ; 2PHG ; 5IY6 ; 5IY7 ; 5IY8 ; 5IY9 ; 5IYA ; 5IYB ; 5IYC ; 5IYD ; 5WH1 ; 6O9L ; 7EDX ; 7EG7 ; 7EG8 ; 7EG9 ; 7EGA ; 7EGB ; 7EGC ; 7ENA ; 7ENC ; 7LBM ; 7NVR ; 7NVS ; 7NVT ; 7NVU ; 7NVY ; 7NVZ ; 7NW0 ; 7ZWC ; 7ZWD ; 7ZX7 ; 7ZX8 ; 7ZXE ; 8BVW ; 8BYQ ; 8BZ1 ; 8GXQ ; 8GXS ; 8WAK ; 8WAL ; 8WAN ; 8WAO ; 8WAP ; 8WAQ ; 8WAR ; 8WAS
• EC Number: 2.3.1.48
• Pfam ID: PF08271 ; PF00382
• Sequence:
  MASTSRLDALPRVTCPNHPDAILVEDYRAGDMICPECGLVVGDRVIDVGSEWRTFSNDKA
  TKDPSRVGDSQNPLLSDGDLSTMIGKGTGAASFDEFGNSKYQNRRTMSSSDRAMMNAFKE
  ITTMADRINLPRNIVDRTNNLFKQVYEQKSLKGRANDAIASACLYIACRQEGVPRTFKEI
  CAVSRISKKEIGRCFKLILKALETSVDLITTGDFMSRFCSNLCLPKQVQMAATHIARKAV
  ELDLVPGRSPISVAAAAIYMASQASAEKRTQKEIGDIAGVADVTIRQSYRLIYPRAPDLF
  PTDFKFDTPVDKLPQL
• Function: General transcription factor that plays a role in transcription initiation by RNA polymerase II (Pol II). Involved in the pre-initiation complex (PIC) formation and Pol II recruitment at promoter DNA. Together with the TATA box-bound TBP forms the core initiation complex and provides a bridge between TBP and the Pol II-TFIIF complex. Released from the PIC early following the onset of transcription during the initiation and elongation transition and reassociates with TBP during the next transcription cycle. Associates with chromatin to core promoter-specific regions. Binds to two distinct DNA core promoter consensus sequence elements in a TBP-independent manner; these IIB-recognition elements (BREs) are localized immediately upstream (BREu), 5'-[GC][GC][GA]CGCC-3', and downstream (BREd), 5'-[GA]T[TGA][TG][GT][TG][TG]-3', of the TATA box element. Modulates transcription start site selection. Exhibits also autoacetyltransferase activity that contributes to the activated transcription.
• Tissue Specificity: Expressed in the inner cell mass forming the embryoblast . Not detected in cells from the outer thin layer trophoblast (at protein level) .
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  Spinocerebellar ataxia (hsa05017)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  RNA Polymerase II HIV Promoter Escape (R-HSA-167162)
  Transcription of the HIV genome (R-HSA-167172)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  RNA polymerase II transcribes snRNA genes (R-HSA-6807505)
  RNA Polymerase II Promoter Escape (R-HSA-73776)
  RNA Polymerase II Transcription Pre-Initiation And Promoter Opening (R-HSA-73779)
  RNA Polymerase II Transcription Initiation (R-HSA-75953)
  RNA Polymerase II Transcription Initiation And Promoter Clearance (R-HSA-76042)
  HIV Transcription Initiation (R-HSA-167161)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[2]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription initiation factor IIB (GTF2B).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transcription initiation factor IIB (GTF2B).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription initiation factor IIB (GTF2B).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transcription initiation factor IIB (GTF2B).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription initiation factor IIB (GTF2B).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Transcription initiation factor IIB (GTF2B).	[12]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transcription initiation factor IIB (GTF2B).	[13]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Transcription initiation factor IIB (GTF2B).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription initiation factor IIB (GTF2B).	[15]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Transcription initiation factor IIB (GTF2B).	[16]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Transcription initiation factor IIB (GTF2B).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription initiation factor IIB (GTF2B).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transcription initiation factor IIB (GTF2B).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transcription initiation factor IIB (GTF2B).	[22]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Transcription initiation factor IIB (GTF2B).	[23]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Transcription initiation factor IIB (GTF2B).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription initiation factor IIB (GTF2B).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transcription initiation factor IIB (GTF2B).	[19]

References

• [1] Label-Free Nanoplasmonic Biosensing of Cancer Biomarkers for Clinical Diagnosis.Methods Mol Biol. 2019;2027:115-140. doi: 10.1007/978-1-4939-9616-2_10.
• [2] Overexpression of TFIIB-related factor 2 is significantly correlated with tumor angiogenesis and poor survival in patients with esophageal squamous cell cancer.Med Oncol. 2013 Jun;30(2):553. doi: 10.1007/s12032-013-0553-4. Epub 2013 Apr 2.
• [3] General transcription factor IIb overexpression and a potential link to proliferation in human hepatocellular carcinoma.Pathol Oncol Res. 2013 Apr;19(2):195-203. doi: 10.1007/s12253-012-9569-x. Epub 2012 Oct 5.
• [4] MicroRNA-373 Inhibits Cell Proliferation and Invasion via Targeting BRF2 in Human Non-small Cell Lung Cancer A549 Cell Line.Cancer Res Treat. 2018 Jul;50(3):936-949. doi: 10.4143/crt.2017.302. Epub 2017 Oct 12.
• [5] The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor IIB.Mol Endocrinol. 2000 Mar;14(3):401-20. doi: 10.1210/mend.14.3.0435.
• [6] A label-free nanostructured plasmonic biosensor based on Blu-ray discs with integrated microfluidics for sensitive biodetection.Biosens Bioelectron. 2017 Oct 15;96:260-267. doi: 10.1016/j.bios.2017.05.020. Epub 2017 May 10.
• [7] 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.
• [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] 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] 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.
• [12] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [13] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [14] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
• [17] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [18] 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.
• [19] 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.
• [20] Exposure to environmental bisphenol A inhibits HTR-8/SVneo cell migration and invasion. J Biomed Res. 2020 Jun 30;34(5):369-378. doi: 10.7555/JBR.34.20200013.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.