Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBFO594)

• DOT Name: Transcription elongation factor A protein 1 (TCEA1)
• Synonyms: Transcription elongation factor S-II protein 1; Transcription elongation factor TFIIS.o
• Gene Name: TCEA1
• Related Disease:
  Rabies
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cystic fibrosis
  Dementia
  Inflammatory bowel disease
  Neoplasm
  Obesity
  Pancreatic cancer
  Rheumatoid arthritis
  Clear cell renal carcinoma
  Gastric cancer
  Melanoma
  Meningioma
  Renal cell carcinoma
  Stomach cancer
  Treacher-Collins syndrome
  Cutaneous mastocytosis
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
• UniProt ID: TCEA1_HUMAN
• PDB ID: 1TFI; 3NDQ; 5IY6; 5IY7; 5IY8; 5IYA; 5IYB; 5IYC; 6O9L; 6ZUY; 6ZV4; 7CNF; 7UNC; 7UND; 8A40
• Pfam ID: PF08711 ; PF01096 ; PF07500
• Sequence:
  MEDEVVRFAKKMDKMVQKKNAAGALDLLKELKNIPMTLELLQSTRIGMSVNAIRKQSTDE
  EVTSLAKSLIKSWKKLLDGPSTEKDLDEKKKEPAITSQNSPEAREESTSSGNVSNRKDET
  NARDTYVSSFPRAPSTSDSVRLKCREMLAAALRTGDDYIAIGADEEELGSQIEEAIYQEI
  RNTDMKYKNRVRSRISNLKDAKNPNLRKNVLCGNIPPDLFARMTAEEMASDELKEMRKNL
  TKEAIREHQMAKTGGTQTDLFTCGKCKKKNCTYTQVQTRSADEPMTTFVVCNECGNRWKF
  C
• 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.
• Reactome Pathway:
  Formation of HIV elongation complex in the absence of HIV Tat (R-HSA-167152)
  Formation of HIV-1 elongation complex containing HIV-1 Tat (R-HSA-167200)
  Pausing and recovery of Tat-mediated HIV elongation (R-HSA-167238)
  Tat-mediated HIV elongation arrest and recovery (R-HSA-167243)
  Tat-mediated elongation of the HIV-1 transcript (R-HSA-167246)
  HIV elongation arrest and recovery (R-HSA-167287)
  Pausing and recovery of HIV elongation (R-HSA-167290)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  Formation of TC-NER Pre-Incision Complex (R-HSA-6781823)
  Transcription-Coupled Nucleotide Excision Repair (TC-NER) (R-HSA-6781827)
  Dual incision in TC-NER (R-HSA-6782135)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  RNA Polymerase II Transcription Elongation (R-HSA-75955)
  Formation of RNA Pol II elongation complex (R-HSA-112382)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rabies	DISSC4V5	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[3]
Dementia	DISXL1WY	Strong	Biomarker	[4]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Obesity	DIS47Y1K	Strong	Biomarker	[7]
Pancreatic cancer	DISJC981	Strong	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[8]
Gastric cancer	DISXGOUK	moderate	Biomarker	[9]
Melanoma	DIS1RRCY	moderate	Biomarker	[10]
Meningioma	DISPT4TG	moderate	Biomarker	[11]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[8]
Stomach cancer	DISKIJSX	moderate	Biomarker	[9]
Treacher-Collins syndrome	DIS2GXZ1	moderate	Genetic Variation	[12]
Cutaneous mastocytosis	DISLBZEF	Limited	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[13]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[14]

10 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 elongation factor A protein 1 (TCEA1).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription elongation factor A protein 1 (TCEA1).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transcription elongation factor A protein 1 (TCEA1).	[17]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Transcription elongation factor A protein 1 (TCEA1).	[18]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transcription elongation factor A protein 1 (TCEA1).	[19]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Transcription elongation factor A protein 1 (TCEA1).	[21]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Transcription elongation factor A protein 1 (TCEA1).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transcription elongation factor A protein 1 (TCEA1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription elongation factor A protein 1 (TCEA1).	[26]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Transcription elongation factor A protein 1 (TCEA1).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Transcription elongation factor A protein 1 (TCEA1).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription elongation factor A protein 1 (TCEA1).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transcription elongation factor A protein 1 (TCEA1).	[25]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Transcription elongation factor A protein 1 (TCEA1).	[25]

References

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• [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] Volumetric capnography versus spirometry for the evaluation of pulmonary function in cystic fibrosis and allergic asthma.J Pediatr (Rio J). 2020 Mar-Apr;96(2):255-264. doi: 10.1016/j.jped.2018.10.008. Epub 2018 Dec 7.
• [4] Balance between innate versus adaptive immune system and the risk of dementia: a population-based cohort study.J Neuroinflammation. 2019 Mar 30;16(1):68. doi: 10.1186/s12974-019-1454-z.
• [5] Suicidal Behavior Among Hospitalized Adults With Inflammatory Bowel Disease: A United States Nationwide Analysis.Inflamm Bowel Dis. 2017 Dec 19;24(1):25-34. doi: 10.1093/ibd/izx005.
• [6] Radiofrequency ablation versus laparoscopic hepatectomy for hepatocellular carcinoma: A real world single center study.Eur J Surg Oncol. 2020 Apr;46(4 Pt A):548-559. doi: 10.1016/j.ejso.2019.10.026. Epub 2019 Oct 24.
• [7] Socioeconomic inequality in childhood obesity and its determinants: a Blinder-Oaxaca decomposition.J Pediatr (Rio J). 2018 Mar-Apr;94(2):131-139. doi: 10.1016/j.jped.2017.03.009. Epub 2017 Aug 18.
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• [9] Systemic immune-inflammation index as a useful prognostic indicator predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy.Cancer Manag Res. 2017 Dec 14;9:849-867. doi: 10.2147/CMAR.S151026. eCollection 2017.
• [10] Anti-metastatic and anti-angiogenic activities of sulfated polysaccharide of Sepiella maindroni ink.Carbohydr Polym. 2013 Jan 2;91(1):403-9. doi: 10.1016/j.carbpol.2012.08.050. Epub 2012 Aug 22.
• [11] Meningioma protein-protein interaction network.Arch Iran Med. 2014 Apr;17(4):262-72.
• [12] Long-term serum platinum changes and their association with cisplatin-related late effects in testicular cancer survivors.Acta Oncol. 2018 Oct;57(10):1392-1400. doi: 10.1080/0284186X.2018.1473641. Epub 2018 May 18.
• [13] Abnormal expression of YEATS4 associates with poor prognosis and promotes cell proliferation of hepatic carcinoma cell by regulation the TCEA1/DDX3 axis.Am J Cancer Res. 2018 Oct 1;8(10):2076-2087. eCollection 2018.
• [14] Sulfated polysaccharide of Sepiella Maindroni ink inhibits the migration, invasion and matrix metalloproteinase-2 expression through suppressing EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells.Int J Biol Macromol. 2018 Feb;107(Pt A):349-362. doi: 10.1016/j.ijbiomac.2017.08.178. Epub 2017 Sep 9.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [19] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [20] 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.
• [21] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [22] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [27] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.