Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLTRSK4)

• DOT Name: Transcription elongation factor A protein 3 (TCEA3)
• Synonyms: Transcription elongation factor S-II protein 3; Transcription elongation factor TFIIS.h
• Gene Name: TCEA3
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Pancreatic cancer
• UniProt ID: TCEA3_HUMAN
• Pfam ID: PF08711 ; PF01096 ; PF07500
• Sequence:
  MGQEEELLRIAKKLEKMVARKNTEGALDLLKKLHSCQMSIQLLQTTRIGVAVNGVRKHCS
  DKEVVSLAKVLIKNWKRLLDSPGPPKGEKGEEREKAKKKEKGLECSDWKPEAGLSPPRKK
  REDPKTRRDSVDSKSSASSSPKRPSVERSNSSKSKAESPKTPSSPLTPTFASSMCLLAPC
  YLTGDSVRDKCVEMLSAALKADDDYKDYGVNCDKMASEIEDHIYQELKSTDMKYRNRVRS
  RISNLKDPRNPGLRRNVLSGAISAGLIAKMTAEEMASDELRELRNAMTQEAIREHQMAKT
  GGTTTDLFQCSKCKKKNCTYNQVQTRSADEPMTTFVLCNECGNRWKFC
• 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.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

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

14 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 elongation factor A protein 3 (TCEA3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription elongation factor A protein 3 (TCEA3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription elongation factor A protein 3 (TCEA3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription elongation factor A protein 3 (TCEA3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription elongation factor A protein 3 (TCEA3).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription elongation factor A protein 3 (TCEA3).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transcription elongation factor A protein 3 (TCEA3).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Transcription elongation factor A protein 3 (TCEA3).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transcription elongation factor A protein 3 (TCEA3).	[11]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Transcription elongation factor A protein 3 (TCEA3).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcription elongation factor A protein 3 (TCEA3).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transcription elongation factor A protein 3 (TCEA3).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription elongation factor A protein 3 (TCEA3).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription elongation factor A protein 3 (TCEA3).	[18]

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 3 (TCEA3).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transcription elongation factor A protein 3 (TCEA3).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transcription elongation factor A protein 3 (TCEA3).	[17]

References

• [1] 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.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17beta-oestradiol in MCF7 human breast cancer cells. J Appl Toxicol. 2007 Jan-Feb;27(1):67-77. doi: 10.1002/jat.1200.
• [8] 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.
• [9] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] 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.
• [12] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.