Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUST8MR)

• DOT Name: Transcription factor EC (TFEC)
• Synonyms: TFE-C; Class E basic helix-loop-helix protein 34; bHLHe34; Transcription factor EC-like; hTFEC-L
• Gene Name: TFEC
• Related Disease:
  Advanced cancer
  Microphthalmia
  Neoplasm
  Coronary heart disease
• UniProt ID: TFEC_HUMAN
• Pfam ID: PF11851 ; PF00010
• Sequence:
  MTLDHQIINPTLKWSQPAVPSGGPLVQHAHTTLDSDAGLTENPLTKLLAIGKEDDNAQWH
  MEDVIEDIIGMESSFKEEGADSPLLMQRTLSGSILDVYSGEQGISPINMGLTSASCPSSL
  PMKREITETDTRALAKERQKKDNHNLIERRRRYNINYRIKELGTLIPKSNDPDMRWNKGT
  ILKASVEYIKWLQKEQQRARELEHRQKKLEQANRRLLLRIQELEIQARTHGLPTLASLGT
  VDLGAHVTKQQSHPEQNSVDYCQQLTVSQGPSPELCDQAIAFSDPLSYFTDLSFSAALKE
  EQRLDGMLLDDTISPFGTDPLLSATSPAVSKESSRRSSFSSDDGDEL
• Function: Transcriptional regulator that acts as a repressor or an activator. Acts as a transcriptional repressor on minimal promoter containing element F (that includes an E-box sequence). Binds to element F in an E-box sequence-specific manner. Acts as a transcriptional transactivator on the proximal promoter region of the tartrate-resistant acid phosphatase (TRAP) E-box containing promoter. Collaborates with MITF in target gene activation. Acts as a transcriptional repressor on minimal promoter containing mu E3 enhancer sequence. Binds to mu E3 DNA sequence of the immunoglobulin heavy-chain gene enhancer. Binds DNA in a homo- or heterodimeric form.
• Tissue Specificity: Expressed moderately in spleen, kidney, bone marrow, small intestine and leukocytes. Expressed weakly in testis, trachea and colon.

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	Definitive	Altered Expression	[1]
Microphthalmia	DISGEBES	Definitive	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcription factor EC (TFEC).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor EC (TFEC).	[6]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Transcription factor EC (TFEC).	[6]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Transcription factor EC (TFEC).	[7]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Transcription factor EC (TFEC).	[6]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Transcription factor EC (TFEC).	[8]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Transcription factor EC (TFEC).	[6]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Transcription factor EC (TFEC).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Transcription factor EC (TFEC).	[9]

References

• [1] The MiTF/TFE Family of Transcription Factors: Master Regulators of Organelle Signaling, Metabolism, and Stress Adaptation.Mol Cancer Res. 2017 Dec;15(12):1637-1643. doi: 10.1158/1541-7786.MCR-17-0320. Epub 2017 Aug 29.
• [2] Nutrient deprivation and lysosomal stress induce activation of TFEB in retinal pigment epithelial cells.Cell Mol Biol Lett. 2019 May 27;24:33. doi: 10.1186/s11658-019-0159-8. eCollection 2019.
• [3] Whole-genome profiling helps to classify phyllodes tumours of the breast.J Clin Pathol. 2016 Dec;69(12):1081-1087. doi: 10.1136/jclinpath-2016-203684. Epub 2016 May 20.
• [4] Integrated microRNA-mRNA analysis of coronary artery disease.Mol Biol Rep. 2014 Aug;41(8):5505-11. doi: 10.1007/s11033-014-3426-9. Epub 2014 Jun 10.
• [5] 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.
• [6] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [7] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [8] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [9] 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.
• [10] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.