Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1OS9TY)

• DOT Name: Transcription elongation factor A protein 2 (TCEA2)
• Synonyms: Testis-specific S-II; Transcription elongation factor S-II protein 2; Transcription elongation factor TFIIS.l
• Gene Name: TCEA2
• Related Disease:
  Acute myelogenous leukaemia
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Pancreatic cancer
• UniProt ID: TCEA2_HUMAN
• PDB ID: 2LW4
• Pfam ID: PF08711 ; PF01096 ; PF07500
• Sequence:
  MMGKEEEIARIARRLDKMVTKKSAEGAMDLLRELKAMPITLHLLQSTRVGMSVNALRKQS
  SDEEVIALAKSLIKSWKKLLDASDAKARERGRGMPLPTSSRDASEAPDPSRKRPELPRAP
  STPRITTFPPVPVTCDAVRNKCREMLTAALQTDHDHVAIGADCERLSAQIEECIFRDVGN
  TDMKYKNRVRSRISNLKDAKNPDLRRNVLCGAITPQQIAVMTSEEMASDELKEIRKAMTK
  EAIREHQMARTGGTQTDLFTCGKCRKKNCTYTQVQTRSSDEPMTTFVVCNECGNRWKFC
• Function: Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by S-II allows the resumption of elongation from the new 3'-terminus.
• Tissue Specificity: Testis and ovary specific.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Pancreatic cancer	DISJC981	Strong	Biomarker	[2]

17 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 Transcription elongation factor A protein 2 (TCEA2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription elongation factor A protein 2 (TCEA2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription elongation factor A protein 2 (TCEA2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription elongation factor A protein 2 (TCEA2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription elongation factor A protein 2 (TCEA2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transcription elongation factor A protein 2 (TCEA2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transcription elongation factor A protein 2 (TCEA2).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transcription elongation factor A protein 2 (TCEA2).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Transcription elongation factor A protein 2 (TCEA2).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transcription elongation factor A protein 2 (TCEA2).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Transcription elongation factor A protein 2 (TCEA2).	[13]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Transcription elongation factor A protein 2 (TCEA2).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Transcription elongation factor A protein 2 (TCEA2).	[13]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Transcription elongation factor A protein 2 (TCEA2).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transcription elongation factor A protein 2 (TCEA2).	[17]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Transcription elongation factor A protein 2 (TCEA2).	[19]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Transcription elongation factor A protein 2 (TCEA2).	[20]

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 Transcription elongation factor A protein 2 (TCEA2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transcription elongation factor A protein 2 (TCEA2).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transcription elongation factor A protein 2 (TCEA2).	[18]

References

• [1] Discovery of epigenetically silenced genes in acute myeloid leukemias.Leukemia. 2007 May;21(5):1026-34. doi: 10.1038/sj.leu.2404611. Epub 2007 Mar 1.
• [2] Knockdown of TFIIS by RNA silencing inhibits cancer cell proliferation and induces apoptosis.BMC Cancer. 2008 May 12;8:133. doi: 10.1186/1471-2407-8-133.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] Effect of ovarian steroids on gene expression profile in human uterine microvascular endothelial cells. Fertil Steril. 2009 Aug;92(2):709-21.
• [10] 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.
• [11] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [12] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [15] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [20] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.