Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMYT3NK)

• DOT Name: Transcription factor AP-2-alpha (TFAP2A)
• Synonyms: AP2-alpha; AP-2 transcription factor; Activating enhancer-binding protein 2-alpha; Activator protein 2; AP-2
• Gene Name: TFAP2A
• Related Disease: Branchiooculofacial syndrome
• UniProt ID: AP2A_HUMAN
• PDB ID: 8J0K; 8J0L; 8J0R
• Pfam ID: PF03299
• Sequence:
  MLWKLTDNIKYEDCEDRHDGTSNGTARLPQLGTVGQSPYTSAPPLSHTPNADFQPPYFPP
  PYQPIYPQSQDPYSHVNDPYSLNPLHAQPQPQHPGWPGQRQSQESGLLHTHRGLPHQLSG
  LDPRRDYRRHEDLLHGPHALSSGLGDLSIHSLPHAIEEVPHVEDPGINIPDQTVIKKGPV
  SLSKSNSNAVSAIPINKDNLFGGVVNPNEVFCSVPGRLSLLSSTSKYKVTVAEVQRRLSP
  PECLNASLLGGVLRRAKSKNGGRSLREKLDKIGLNLPAGRRKAANVTLLTSLVEGEAVHL
  ARDFGYVCETEFPAKAVAEFLNRQHSDPNEQVTRKNMLLATKQICKEFTDLLAQDRSPLG
  NSRPNPILEPGIQSCLTHFNLISHGFGSPAVCAAVTALQNYLTEALKAMDKMYLSNNPNS
  HTDNNAKSSDKEEKHRK
• 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-alpha is the only AP-2 protein required for early morphogenesis of the lens vesicle. Together with the CITED2 coactivator, stimulates the PITX2 P1 promoter transcription activation. Associates with chromatin to the PITX2 P1 promoter region.
• Reactome Pathway:
  Negative regulation of activity of TFAP2 (AP-2) family transcription factors (R-HSA-8866904)
  TFAP2 (AP-2) family regulates transcription of other transcription factors (R-HSA-8866906)
  Activation of the TFAP2 (AP-2) family of transcription factors (R-HSA-8866907)
  TFAP2 (AP-2) family regulates transcription of growth factors and their receptors (R-HSA-8866910)
  TFAP2 (AP-2) family regulates transcription of cell cycle factors (R-HSA-8866911)
  TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation (R-HSA-8869496)
  Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors (R-HSA-8864260)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Branchiooculofacial syndrome	DISHJ9O9	Definitive	Autosomal dominant	[1]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Transcription factor AP-2-alpha (TFAP2A) increases the response to substance of Etoposide.	[6]
Mitomycin	DMH0ZJE	Approved	Transcription factor AP-2-alpha (TFAP2A) affects the response to substance of Mitomycin.	[29]
Gemcitabine	DMSE3I7	Approved	Transcription factor AP-2-alpha (TFAP2A) increases the response to substance of Gemcitabine.	[30]
VRX496	DMIO4V5	Approved	Transcription factor AP-2-alpha (TFAP2A) increases the Insulin resistance ADR of VRX496.	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Transcription factor AP-2-alpha (TFAP2A).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transcription factor AP-2-alpha (TFAP2A).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Transcription factor AP-2-alpha (TFAP2A).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[10]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[14]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[15]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[16]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[6]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[3]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[3]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[3]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[17]
Mestranol	DMG3F94	Approved	Mestranol decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[7]
Paroxetine	DM5PVQE	Approved	Paroxetine increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[10]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[10]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[19]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[7]
PD-153035	DM7KJTI	Discontinued in Phase 1	PD-153035 decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[21]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[23]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[24]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Transcription factor AP-2-alpha (TFAP2A).	[25]
RGD	DMFASRB	Investigative	RGD decreases the expression of Transcription factor AP-2-alpha (TFAP2A).	[28]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the stability of Transcription factor AP-2-alpha (TFAP2A).	[26]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate affects the localization of Transcription factor AP-2-alpha (TFAP2A).	[27]

References

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