Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX24CQI)

• DOT Name: Transcription elongation factor A protein-like 4 (TCEAL4)
• Synonyms: TCEA-like protein 4; Transcription elongation factor S-II protein-like 4
• Gene Name: TCEAL4
• Related Disease:
  Differentiated thyroid carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland undifferentiated (anaplastic) carcinoma
• UniProt ID: TCAL4_HUMAN
• Pfam ID: PF04538
• Sequence:
  MEKLYSENEGMASNQGKMENEEQPQDERKPEVTCTLEDKKLENEGKTENKGKTGDEEMLK
  DKGKPESEGEAKEGKSEREGESEMEGGSEREGKPEIEGKPESEGEPGSETRAAGKRPAED
  DVPRKAKRKTNKGLAHYLKEYKEAIHDMNFSNEDMIREFDNMAKVQDEKRKSKQKLGAFL
  WMQRNLQDPFYPRGPREFRGGCRAPRRDIEDIPYV
• Function: May be involved in transcriptional regulation.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Differentiated thyroid carcinoma	DIS1V20Y	Strong	Altered Expression	[1]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[1]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[1]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Transcription elongation factor A protein-like 4 (TCEAL4).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription elongation factor A protein-like 4 (TCEAL4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transcription elongation factor A protein-like 4 (TCEAL4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription elongation factor A protein-like 4 (TCEAL4).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transcription elongation factor A protein-like 4 (TCEAL4).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Transcription elongation factor A protein-like 4 (TCEAL4).	[7]

3 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 elongation factor A protein-like 4 (TCEAL4).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transcription elongation factor A protein-like 4 (TCEAL4).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Transcription elongation factor A protein-like 4 (TCEAL4).	[9]

References

• [1] Down-regulation of transcription elogation factor A (SII) like 4 (TCEAL4) in anaplastic thyroid cancer.BMC Cancer. 2006 Nov 1;6:260. doi: 10.1186/1471-2407-6-260.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] 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.
• [9] 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.