Details of Drug Off-Target (DOT)

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

• DOT Name: Transcription factor IIIA (GTF3A)
• Synonyms: TFIIIA
• Gene Name: GTF3A
• Related Disease:
  Malaria
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  HIV infectious disease
  Hyperinsulinemia
  Knee osteoarthritis
  Non-insulin dependent diabetes
  Obesity
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
  Neoplasm
• UniProt ID: TF3A_HUMAN
• Pfam ID: PF00096
• Sequence:
  MDPPAVVAESVSSLTIADAFIAAGESSAPTPPRPALPRRFICSFPDCSANYSKAWKLDAH
  LCKHTGERPFVCDYEGCGKAFIRDYHLSRHILTHTGEKPFVCAANGCDQKFNTKSNLKKH
  FERKHENQQKQYICSFEDCKKTFKKHQQLKIHQCQHTNEPLFKCTQEGCGKHFASPSKLK
  RHAKAHEGYVCQKGCSFVAKTWTELLKHVRETHKEEILCEVCRKTFKRKDYLKQHMKTHA
  PERDVCRCPREGCGRTYTTVFNLQSHILSFHEESRPFVCEHAGCGKTFAMKQSLTRHAVV
  HDPDKKKMKLKVKKSREKRSLASHLSGYIPPKRKQGQGLSLCQNGESPNCVEDKMLSTVA
  VLTLG
• Function: Involved in ribosomal large subunit biogenesis. Binds the approximately 50 base pairs internal control region (ICR) of 5S ribosomal RNA genes. It is required for their RNA polymerase III-dependent transcription and may also maintain the transcription of other genes. Also binds the transcribed 5S RNA's.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway:
  RNA Polymerase III Transcription Initiation From Type 1 Promoter (R-HSA-76061)
  RNA Polymerase III Abortive And Retractive Initiation (R-HSA-749476)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[3]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
HIV infectious disease	DISO97HC	Strong	Biomarker	[5]
Hyperinsulinemia	DISIDWT6	Strong	Altered Expression	[6]
Knee osteoarthritis	DISLSNBJ	Strong	Altered Expression	[7]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[8]
Obesity	DIS47Y1K	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Altered Expression	[9]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[9]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[10]
Neoplasm	DISZKGEW	Limited	Biomarker	[11]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Transcription factor IIIA (GTF3A) affects the response to substance of Vinblastine.	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Transcription factor IIIA (GTF3A).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor IIIA (GTF3A).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcription factor IIIA (GTF3A).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor IIIA (GTF3A).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor IIIA (GTF3A).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription factor IIIA (GTF3A).	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Transcription factor IIIA (GTF3A).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transcription factor IIIA (GTF3A).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription factor IIIA (GTF3A).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcription factor IIIA (GTF3A).	[22]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Transcription factor IIIA (GTF3A).	[23]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Transcription factor IIIA (GTF3A).	[24]

1 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 factor IIIA (GTF3A).	[19]

References

• [1] Malaria parasites possess a telomere repeat-binding protein that shares ancestry with transcription factor IIIA.Nat Microbiol. 2017 Mar 13;2:17033. doi: 10.1038/nmicrobiol.2017.33.
• [2] A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma.J Exp Med. 1999 Apr 5;189(7):1101-10. doi: 10.1084/jem.189.7.1101.
• [3] Common genetic variants in fatty acid-binding protein-4 (FABP4) and clinical diabetes risk in the Women's Health Initiative Observational Study.Obesity (Silver Spring). 2010 Sep;18(9):1812-20. doi: 10.1038/oby.2009.496. Epub 2010 Jan 28.
• [4] AP2 Transcription Factors Regulate Expression of CRABPII in hormone responsive breast carcinoma. J Surg Res. 2007 Mar;138(1):71-8.
• [5] Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.J Virol. 2004 Sep;78(17):9458-73. doi: 10.1128/JVI.78.17.9458-9473.2004.
• [6] Adipocyte-derived stem cell-based gene therapy upon adipogenic differentiation on microcarriers attenuates type 1 diabetes in mice.Stem Cell Res Ther. 2019 Jan 22;10(1):36. doi: 10.1186/s13287-019-1135-y.
• [7] Effects of ultrasound therapy on the synovial fluid proteome in a rabbit surgery-induced model of knee osteoarthritis.Biomed Eng Online. 2019 Feb 22;18(1):18. doi: 10.1186/s12938-019-0637-2.
• [8] Translocase of inner mitochondrial membrane 44 alters the mitochondrial fusion and fission dynamics and protects from type 2 diabetes.Metabolism. 2015 Jun;64(6):677-88. doi: 10.1016/j.metabol.2015.02.004. Epub 2015 Feb 23.
• [9] KAI1 promoter activity is dependent on p53, junB and AP2: evidence for a possible mechanism underlying loss of KAI1 expression in cancer cells.Oncogene. 2005 Jan 20;24(4):637-49. doi: 10.1038/sj.onc.1208216.
• [10] Novel polymorphisms of the AP-2 gene (6p24): analysis of association with schizophrenia.J Hum Genet. 2000;45(1):24-30. doi: 10.1007/s100380050005.
• [11] Expression pattern of AP-2 transcription factors in cervical cancer cells and analysis of their influence on human papillomavirus oncogene transcription.J Mol Med (Berl). 2001 Jun;79(5-6):314-20. doi: 10.1007/s001090100211.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [15] 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.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [18] Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
• [19] 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.
• [20] 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.
• [21] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [22] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [23] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [24] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [25] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.