Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUDIW05)

• DOT Name: Transcription factor AP-2 gamma (TFAP2C)
• Synonyms: AP2-gamma; Activating enhancer-binding protein 2 gamma; Transcription factor ERF-1
• Gene Name: TFAP2C
• Related Disease:
  Neoplasm
  Adult teratoma
  Aplasia cutis congenita
  Breast carcinoma
  Colorectal carcinoma
  Corpus callosum, agenesis of
  Endometrial cancer
  Hepatocellular carcinoma
  Her2-receptor negative breast cancer
  HER2/NEU overexpressing breast cancer
  Leiomyoma
  Lung adenocarcinoma
  Seminoma
  Teratoma
  Uterine fibroids
  Advanced cancer
  Bladder cancer
  Breast neoplasm
  Carcinoma
  Lung carcinoma
  Melanoma
  Tetralogy of fallot
  Urinary bladder cancer
  Urinary bladder neoplasm
  Endometrial carcinoma
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Lung cancer
  Matthew-Wood syndrome
  Myeloid neoplasm
  Neuroblastoma
  Non-small-cell lung cancer
  Pancreatic ductal carcinoma
  T-cell acute lymphoblastic leukaemia
• UniProt ID: AP2C_HUMAN
• Pfam ID: PF03299
• Sequence:
  MLWKITDNVKYEEDCEDRHDGSSNGNPRVPHLSSAGQHLYSPAPPLSHTGVAEYQPPPYF
  PPPYQQLAYSQSADPYSHLGEAYAAAINPLHQPAPTGSQQQAWPGRQSQEGAGLPSHHGR
  PAGLLPHLSGLEAGAVSARRDAYRRSDLLLPHAHALDAAGLAENLGLHDMPHQMDEVQNV
  DDQHLLLHDQTVIRKGPISMTKNPLNLPCQKELVGAVMNPTEVFCSVPGRLSLLSSTSKY
  KVTVAEVQRRLSPPECLNASLLGGVLRRAKSKNGGRSLREKLDKIGLNLPAGRRKAAHVT
  LLTSLVEGEAVHLARDFAYVCEAEFPSKPVAEYLTRPHLGGRNEMAARKNMLLAAQQLCK
  EFTELLSQDRTPHGTSRLAPVLETNIQNCLSHFSLITHGFGSQAICAAVSALQNYIKEAL
  IVIDKSYMNPGDQSPADSNKTLEKMEKHRK
• 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. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer.
• 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)
  Specification of primordial germ cells (R-HSA-9827857)
  SUMOylation of transcription factors (R-HSA-3232118)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Adult teratoma	DISBY81U	Strong	Altered Expression	[2]
Aplasia cutis congenita	DISMDAYM	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[5]
Corpus callosum, agenesis of	DISO9P40	Strong	Altered Expression	[3]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Her2-receptor negative breast cancer	DISS605N	Strong	Biomarker	[8]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Biomarker	[8]
Leiomyoma	DISLDDFN	Strong	Altered Expression	[9]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[10]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[11]
Teratoma	DIS6ICY4	Strong	Altered Expression	[2]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[9]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[12]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[1]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[13]
Carcinoma	DISH9F1N	moderate	Altered Expression	[3]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[14]
Melanoma	DIS1RRCY	moderate	Biomarker	[15]
Tetralogy of fallot	DISMHFNW	moderate	Altered Expression	[16]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[1]
Urinary bladder neoplasm	DIS7HACE	moderate	Altered Expression	[1]
Endometrial carcinoma	DISXR5CY	Limited	Altered Expression	[6]
Gastric cancer	DISXGOUK	Limited	Biomarker	[17]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[17]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[17]
Lung cancer	DISCM4YA	Limited	Biomarker	[18]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[19]
Myeloid neoplasm	DIS2YOWO	Limited	Biomarker	[20]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[21]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[18]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[19]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Altered Expression	[22]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Transcription factor AP-2 gamma (TFAP2C) affects the response to substance of DTI-015.	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor AP-2 gamma (TFAP2C).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transcription factor AP-2 gamma (TFAP2C).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[26]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[27]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transcription factor AP-2 gamma (TFAP2C).	[28]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transcription factor AP-2 gamma (TFAP2C).	[29]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[30]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription factor AP-2 gamma (TFAP2C).	[31]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[17]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[30]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Transcription factor AP-2 gamma (TFAP2C).	[26]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[26]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Transcription factor AP-2 gamma (TFAP2C).	[33]
Estrone	DM5T6US	Approved	Estrone increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[26]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[26]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[26]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[34]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[30]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor AP-2 gamma (TFAP2C).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor AP-2 gamma (TFAP2C).	[38]

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 affects the methylation of Transcription factor AP-2 gamma (TFAP2C).	[35]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Transcription factor AP-2 gamma (TFAP2C).	[36]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Transcription factor AP-2 gamma (TFAP2C).	[39]

References

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• [5] TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway.J Exp Clin Cancer Res. 2018 Feb 13;37(1):27. doi: 10.1186/s13046-018-0683-9.
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