Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA4B1SG)

• DOT Name: Transcription factor AP-2-epsilon (TFAP2E)
• Synonyms: AP2-epsilon; Activating enhancer-binding protein 2-epsilon
• Gene Name: TFAP2E
• Related Disease:
  Neoplasm
  Adenoma
  Advanced cancer
  Colorectal carcinoma
  Neuroblastoma
  Skin neoplasm
  Gonorrhea
  Gastric cancer
  Stomach cancer
• UniProt ID: AP2E_HUMAN
• Pfam ID: PF03299
• Sequence:
  MLVHTYSAMERPDGLGAAAGGARLSSLPQAAYGPAPPLCHTPAATAAAEFQPPYFPPPYP
  QPPLPYGQAPDAAAAFPHLAGDPYGGLAPLAQPQPPQAAWAAPRAAARAHEEPPGLLAPP
  ARALGLDPRRDYATAVPRLLHGLADGAHGLADAPLGLPGLAAAPGLEDLQAMDEPGMSLL
  DQSVIKKVPIPSKASSLSALSLAKDSLVGGITNPGEVFCSVPGRLSLLSSTSKYKVTVGE
  VQRRLSPPECLNASLLGGVLRRAKSKNGGRCLRERLEKIGLNLPAGRRKAANVTLLTSLV
  EGEAVHLARDFGYVCETEFPAKAAAEYLCRQHADPGELHSRKSMLLAAKQICKEFADLMA
  QDRSPLGNSRPALILEPGVQSCLTHFSLITHGFGGPAICAALTAFQNYLLESLKGLDKMF
  LSSVGSGHGETKASEKDAKHRK
• Function: Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-epsilon may play a role in the development of the CNS and in cartilage differentiation.
• Tissue Specificity: Expressed in skin, primary keratinocytes, immortalized keratinocytes, and HeLa cell line.
• Reactome Pathway:
  Activation of the TFAP2 (AP-2) family of transcription factors (R-HSA-8866907)
  Negative regulation of activity of TFAP2 (AP-2) family transcription factors (R-HSA-8866904)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[1]
Skin neoplasm	DIS16DDV	Strong	Altered Expression	[1]
Gonorrhea	DISQ5AO6	Disputed	Genetic Variation	[3]
Gastric cancer	DISXGOUK	Limited	Biomarker	[5]
Stomach cancer	DISKIJSX	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription factor AP-2-epsilon (TFAP2E).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor AP-2-epsilon (TFAP2E).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcription factor AP-2-epsilon (TFAP2E).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor AP-2-epsilon (TFAP2E).	[10]

1 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 factor AP-2-epsilon (TFAP2E).	[9]

References

• [1] Depletion of TFAP2E attenuates adriamycin-mediated apoptosis in human neuroblastoma cells.Oncol Rep. 2017 Apr;37(4):2459-2464. doi: 10.3892/or.2017.5477. Epub 2017 Feb 24.
• [2] Quantitative, genome-wide analysis of the DNA methylome in sporadic pituitary adenomas.Endocr Relat Cancer. 2012 Nov 19;19(6):805-16. doi: 10.1530/ERC-12-0251. Print 2012 Dec.
• [3] Efficacy of decitabine-loaded gelatinases-stimuli nanoparticles in overcoming cancer drug resistance is mediated via its enhanced demethylating activity to transcription factor AP-2 epsilon.Oncotarget. 2017 Sep 26;8(70):114495-114505. doi: 10.18632/oncotarget.21274. eCollection 2017 Dec 29.
• [4] TFAP2E methylation status and prognosis of patients with radically resected colorectal cancer.Oncology. 2015;88(2):122-32. doi: 10.1159/000362820. Epub 2014 Oct 23.
• [5] TFAP2E methylation promotes 5fluorouracil resistance via exosomal miR?06a?p and miR?21 in gastric cancer MGC?03 cells.Mol Med Rep. 2019 Jul;20(1):323-331. doi: 10.3892/mmr.2019.10237. Epub 2019 May 14.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.