Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors (Homo sapiens)

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1, 3, 5, 7, 8, 10...39, 4237364, 6, 18, 24, 29...4311, 31164311, 3136433039, 4239, 4212, 13, 19, 238, 14, 454017, 33, 35123, 9143364339, 4273, 92, 4414310, 22168, 14, 16, 454317342021, 28, 38343015, 26123715, 26cytosolendoplasmic reticulum lumenmitochondrial matrixnucleoplasmKDM5B TFAP2D KDM5BTFAP2 homo- andheterodimers:KCTD15TFAP2Chomodimer:MYC:KDM5B:CDKN1A geneTFAP2A CITED2 CGA GeneTFAP2A,(TFAP2B,TFAP2C) homo- and heterodimers:YY1:ERBB2 geneKIT Gene KDM5B TFAP2A,TFAP2Chomodimers:CITED2CGATFAP2A-1 ATAD2:ESR1MYBL2CREBBP TFAP2C TFAP2B homodimerERBB2 Gene NPM1TFAP2CTFAP2C SUMO1-K10-TFAP2C VEGFA gene ERBB2TFAP2A,TFAP2Chomodimers:CGA GeneESR1 Gene TFAP2B TFAP2D TFAP2A homodimerTFAP2 homo- andheterodimers:KCTD1TFAP2A CITED4 UBE2I-G97-SUMO1 TFAP2C TFAP2B TFAP2A,TFAP2Chomodimers:ESR1GeneSUMO1-C93-UBE2I NPM1 TFAP2A TFAP2A SUMO1:C93-UBE2IatRATFAP2C TFAP2B TFAP2C MYBL2 gene KCTD15 KITEGFRSUMO1-K10-TFAP2A-1 TFAP2A NOP2TFAP2C APOE gene ESR1 GeneCITED2 CITED2,CITED4,(CITED1)TFAP2A SUMO1-C93-UBE2I NPM1:TFAP2Ahomodimer:HSPD1geneTFAP2Ahomodimer:CDKN1AgeneTFAP2A-1 homodimerUBE2ITFAP2E TFAP2A TFAP2C TFAP2C homodimerPITX2NPM1 CGB3TFAP2C NOP2 geneTFAP2C DEKCITED1 ERBB2 GeneHSPD1UBE2IVEGFAYY1 TFAP2A,TFAP2ChomodimersTFAP2B CITED1 TFAP2C CGB3 GeneCGA Gene TFAP2C TFAP2A TFAP2B SUMO1:C93-UBE2IWWOXTFAP2B UBE2ITFAP2TFAP2A,TFAP2Chomodimers:CITED2:PITX2 GeneYY1VEGFA geneTFAP2D CITED2 CDKN1A geneEP300 TFAP2C TFAP2A PITX2 GeneCITED2 TFAP2Bhomodimer:YEATS4MYCTFAP2B TFAP2A NOP2 gene TFAP2E WWOX EP300KCTD1CGB3 Gene TFAP2Chomodimer:MYC:KDM5BTFAP2C TGFA precursorSUMO1:TFAP2A-1homodimerTFAP2A TFAP2A TFAP2A DEK TFAP2A UBE2I-G97-SUMO1 TFAP2A TFAP2B-G97-SUMO1 EGFR gene KCTD15MYC CGB3 SUMO1:TFAP2ChomodimerCREBBPTFAP2E TFAP2A TFAP2C UBE2I-G97-SUMO1 GonadotropinATAD2 NPM1:TFAP2Ahomodimer:NOP2 geneTFAP2C TFAP2B TFAP2A CDKN1ATFAP2E EGFR geneYEATS4 APOE geneTFAP2A TFAP2D NPM1:TFAP2AhomodimerTFAP2A DEK TFAP2D TFAP2Ahomodimer:VEGFAGeneTFAP2A,(TFAP2B,TFAP2C) homo- and heterodimersCGA TFAP2B TFAP2C SUMO1:C93-UBE2IHSPD1 gene KIT GeneTFAP2C:WWOXTFAP2A APOESUMO1:TFAP2BhomodimerESR1TFAP2A TFAP2A-1-G97-SUMO1 MYBL2 geneTFAP2A SUMO1-C93-UBE2I TFAP2E TFAP2A,(TFAP2B)homodimersTFAP2homo-andheterodimers:CITED2,CITED4,(CITED1):EP300:CREBBPTFAP2A TFAP2A,(TFAP2B)homodimers:KIT geneHSPD1 geneKCTD1 TFAP2A YEATS4TFAP2Chomodimer:EGFR geneTGFA Gene TFAP2C ESR1 TFAP2C-G97-SUMO1 TFAP2B CDKN1A gene TFAP2C PITX2 Gene CITED4 TFAP2CNPM1 TGFA GeneTFAP2A TFAP2A,TFAP2Chomodimers:CGB geneTFAP2 homo- andheterodimersCDKN1A gene DEK:TFAP2A homodimerDEK:TFAP2Ahomodimer:APOE geneSUMO1-K21-TFAP2B TFAP2B NPM1 ATAD2MYC NPM1:TFAP2Ahomodimer:MYBL2geneTFAP2Ahomodimer:TGFA gene373, 9324074312, 1916139, 4230203410, 223243431715, 2639, 4215, 2636128, 14, 454311, 3116323632


Description

The AP-2 (TFAP2) family of transcription factors includes five proteins in mammals: TFAP2A (AP-2 alpha), TFAP2B (AP-2 beta), TFAP2C (AP-2 gamma), TFAP2D (AP-2 delta) and TFAP2E (AP-2 epsilon). The AP-2 family transcription factors are evolutionarily conserved in metazoans and are characterized by a helix-span-helix motif at the C-terminus, a central basic region, and the transactivation domain at the N-terminus. The helix-span-helix motif and the basic region enable dimerization and DNA binding (Eckert et al. 2005).

AP-2 dimers bind palindromic GC-rich DNA response elements that match the consensus sequence 5'-GCCNNNGGC-3' (Williams and Tjian 1991a, Williams and Tjian 1991b). Transcriptional co-factors from the CITED family interact with the helix-span-helix (HSH) domain of TFAP2 (AP-2) family of transcription factors and recruit transcription co-activators EP300 (p300) and CREBBP (CBP) to TFAP2-bound DNA elements. CITED2 shows the highest affinity for TFAP2 proteins, followed by CITED4, while CITED1 interacts with TFAP2s with a very low affinity. Mouse embryos defective for CITED2 exhibit neural crest defects, cardiac malformations and adrenal agenesis, which can at least in part be attributed to a defective Tfap2 transactivation (Bamforth et al. 2001, Braganca et al. 2002, Braganca et al. 2003). Transcriptional activity of AP-2 dimers in inhibited by binding of KCTD1 or KCTD15 to the AP-2 transactivation domain (Ding et al. 2009, Zarelli and Dawid 2013). Transcriptional activity of TFAP2A, TFAP2B and TFAP2C is negatively regulated by SUMOylation mediated by UBE2I (UBC9) (Eloranta and Hurst 2002, Berlato et al. 2011, Impens et al. 2014, Bogachek et al. 2014).<p>During embryonic development, AP-2 transcription factors stimulate proliferation and suppress terminal differentiation in a cell-type specific manner (Eckert et al. 2005).<p>TFAP2A and TFAP2C directly stimulate transcription of the estrogen receptor ESR1 gene (McPherson and Weigel 1999). TFAP2A expression correlates with ESR1 expression in breast cancer, and TFAP2C is frequently overexpressed in estrogen-positive breast cancer and endometrial cancer (deConinck et al. 1995, Turner et al. 1998). TFAP2A, TFAP2C, as well as TFAP2B can directly stimulate the expression of ERBB2, another important breast cancer gene (Bosher et al. 1996). Association of TFAP2A with the YY1 transcription factor significantly increases the ERBB2 transcription rate (Begon et al. 2005). In addition to ERBB2, the expression of another receptor tyrosine kinase, KIT, is also stimulated by TFAP2A and TFAP2B (Huang et al. 1998), while the expression of the VEGF receptor tyrosine kinase ligand VEGFA is repressed by TFAP2A (Ruiz et al. 2004, Li et al. 2012). TFAP2A stimulates transcription of the transforming growth factor alpha (TGFA) gene (Wang et al. 1997). TFAP2C regulates EGFR in luminal breast cancer (De Andrade et al. 2016).<p>TFAP2C plays a critical role in maintaining the luminal phenotype in human breast cancer and in influencing the luminal cell phenotype during normal mammary development (Cyr et al. 2015).<p>In placenta, TFAP2A and TFAP2C directly stimulate transcription of both subunits of the human chorionic gonadotropin, CGA and CGB (Johnson et al. 1997, LiCalsi et al. 2000).<p>TFAP2A and/or TFAP2C, in complex with CITED2, stimulate transcription of the PITX2 gene, involved in left-right patterning and heart development (Bamforth et al. 2004, Li et al. 2012).<p>TFAP2A and TFAP2C play opposing roles in transcriptional regulation of the CDKN1A (p21) gene locus. While TFAP2A stimulates transcription of the CDKN1A cyclin-dependent kinase inhibitor (Zeng et al. 1997, Williams et al. 2009, Scibetta et al. 2010), TFAP2C represses CDKN1A transcription (Williams et al. 2009, Scibetta et al. 2010, Wong et al. 2012). Transcription of the TFAP2A gene may be inhibited by CREB and E2F1 (Melnikova et al. 2010).<p>For review of the AP-2 family of transcription factors, please refer to Eckert et al. 2005. View original pathway at:Reactome.</div>

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 8864260
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Orlic-Milacic, Marija

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Bibliography

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History

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CompareRevisionActionTimeUserComment
101554view11:42, 1 November 2018ReactomeTeamreactome version 66
101090view21:25, 31 October 2018ReactomeTeamreactome version 65
100619view19:59, 31 October 2018ReactomeTeamreactome version 64
100170view16:44, 31 October 2018ReactomeTeamreactome version 63
99720view15:11, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93479view11:24, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
APOE gene ProteinENSG00000130203 (Ensembl)
APOE geneGeneProductENSG00000130203 (Ensembl)
APOEProteinP02649 (Uniprot-TrEMBL)
ATAD2 ProteinQ6PL18 (Uniprot-TrEMBL)
ATAD2:ESR1ComplexR-HSA-8937396 (Reactome)
ATAD2ProteinQ6PL18 (Uniprot-TrEMBL)
CDKN1A gene ProteinENSG00000124762 (Ensembl)
CDKN1A geneGeneProductENSG00000124762 (Ensembl)
CDKN1AProteinP38936 (Uniprot-TrEMBL)
CGA Gene ProteinENSG00000135346 (Ensembl)
CGA GeneGeneProductENSG00000135346 (Ensembl)
CGA ProteinP01215 (Uniprot-TrEMBL)
CGAProteinP01215 (Uniprot-TrEMBL)
CGB3 Gene ProteinENSG00000104827 (Ensembl)
CGB3 GeneGeneProductENSG00000104827 (Ensembl)
CGB3 ProteinP0DN86 (Uniprot-TrEMBL)
CGB3ProteinP0DN86 (Uniprot-TrEMBL)
CITED1 ProteinQ99966 (Uniprot-TrEMBL)
CITED2 ProteinQ99967 (Uniprot-TrEMBL)
CITED2,CITED4,(CITED1)ComplexR-HSA-8864305 (Reactome)
CITED4 ProteinQ96RK1 (Uniprot-TrEMBL)
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
CREBBPProteinQ92793 (Uniprot-TrEMBL)
DEK ProteinP35659 (Uniprot-TrEMBL)
DEK:TFAP2A homodimer:APOE geneComplexR-HSA-8869574 (Reactome)
DEK:TFAP2A homodimerComplexR-HSA-8869593 (Reactome)
DEKProteinP35659 (Uniprot-TrEMBL)
EGFR gene ProteinENSG00000146648 (Ensembl)
EGFR geneGeneProductENSG00000146648 (Ensembl)
EGFRProteinP00533 (Uniprot-TrEMBL)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
EP300ProteinQ09472 (Uniprot-TrEMBL)
ERBB2 Gene ProteinENSG00000141736 (Ensembl)
ERBB2 GeneGeneProductENSG00000141736 (Ensembl)
ERBB2ProteinP04626 (Uniprot-TrEMBL)
ESR1 Gene ProteinENSG00000091831 (Ensembl)
ESR1 GeneGeneProductENSG00000091831 (Ensembl)
ESR1 ProteinP03372 (Uniprot-TrEMBL)
ESR1ProteinP03372 (Uniprot-TrEMBL)
GonadotropinComplexR-HSA-378941 (Reactome)
HSPD1 gene ProteinENSG00000144381 (Ensembl)
HSPD1 geneGeneProductENSG00000144381 (Ensembl)
HSPD1ProteinP10809 (Uniprot-TrEMBL)
KCTD1 ProteinQ719H9 (Uniprot-TrEMBL)
KCTD15 ProteinQ96SI1 (Uniprot-TrEMBL)
KCTD15ProteinQ96SI1 (Uniprot-TrEMBL)
KCTD1ProteinQ719H9 (Uniprot-TrEMBL)
KDM5B ProteinQ9UGL1 (Uniprot-TrEMBL)
KDM5BProteinQ9UGL1 (Uniprot-TrEMBL)
KIT Gene ProteinENSG00000157404 (Ensembl)
KIT GeneGeneProductENSG00000157404 (Ensembl)
KITProteinP10721 (Uniprot-TrEMBL)
MYBL2 gene ProteinENSG00000101057 (Ensembl)
MYBL2 geneGeneProductENSG00000101057 (Ensembl)
MYBL2ProteinP10244 (Uniprot-TrEMBL)
MYC ProteinP01106 (Uniprot-TrEMBL)
MYCProteinP01106 (Uniprot-TrEMBL)
NOP2 gene ProteinENSG00000111641 (Ensembl)
NOP2 geneGeneProductENSG00000111641 (Ensembl)
NOP2ProteinP46087 (Uniprot-TrEMBL)
NPM1 ProteinP06748 (Uniprot-TrEMBL)
NPM1:TFAP2A

homodimer:HSPD1

gene
ComplexR-HSA-8869545 (Reactome)
NPM1:TFAP2A

homodimer:MYBL2

gene
ComplexR-HSA-8869540 (Reactome)
NPM1:TFAP2A homodimer:NOP2 geneComplexR-HSA-8869544 (Reactome)
NPM1:TFAP2A homodimerComplexR-HSA-8869555 (Reactome)
NPM1ProteinP06748 (Uniprot-TrEMBL)
PITX2 Gene ProteinENSG00000164093 (Ensembl)
PITX2 GeneGeneProductENSG00000164093 (Ensembl)
PITX2ProteinQ99697 (Uniprot-TrEMBL)
SUMO1-C93-UBE2I ProteinP63279 (Uniprot-TrEMBL)
SUMO1-K10-TFAP2A-1 ProteinP05549-1 (Uniprot-TrEMBL)
SUMO1-K10-TFAP2C ProteinQ92754 (Uniprot-TrEMBL)
SUMO1-K21-TFAP2B ProteinQ92481 (Uniprot-TrEMBL)
SUMO1:C93-UBE2IComplexR-HSA-2993783 (Reactome)
SUMO1:TFAP2A-1 homodimerComplexR-HSA-8865819 (Reactome)
SUMO1:TFAP2B homodimerComplexR-HSA-8865823 (Reactome)
SUMO1:TFAP2C homodimerComplexR-HSA-8865822 (Reactome)
TFAP2

homo- and

heterodimers:CITED2,CITED4,(CITED1):EP300:CREBBP
ComplexR-HSA-8864321 (Reactome)
TFAP2 homo- and heterodimers:KCTD15ComplexR-HSA-8864359 (Reactome)
TFAP2 homo- and heterodimers:KCTD1ComplexR-HSA-8864347 (Reactome)
TFAP2 homo- and heterodimersComplexR-HSA-8864283 (Reactome)
TFAP2A

homodimer:CDKN1A

gene
ComplexR-HSA-8865245 (Reactome)
TFAP2A homodimer:TGFA geneComplexR-HSA-8864985 (Reactome)
TFAP2A

homodimer:VEGFA

Gene
ComplexR-HSA-8864742 (Reactome)
TFAP2A ProteinP05549 (Uniprot-TrEMBL)
TFAP2A homodimerComplexR-HSA-8864382 (Reactome)
TFAP2A,(TFAP2B) homodimers:KIT geneComplexR-HSA-8864692 (Reactome)
TFAP2A,(TFAP2B) homodimersComplexR-HSA-8864685 (Reactome)
TFAP2A,(TFAP2B,TFAP2C) homo- and heterodimers:YY1:ERBB2 geneComplexR-HSA-8864446 (Reactome)
TFAP2A,(TFAP2B,TFAP2C) homo- and heterodimersComplexR-HSA-8864454 (Reactome)
TFAP2A,TFAP2C homodimers:CGA GeneComplexR-HSA-8864406 (Reactome)
TFAP2A,TFAP2C homodimers:CGB geneComplexR-HSA-8864422 (Reactome)
TFAP2A,TFAP2C homodimers:CITED2:PITX2 GeneComplexR-HSA-8864705 (Reactome)
TFAP2A,TFAP2C homodimers:CITED2ComplexR-HSA-8864723 (Reactome)
TFAP2A,TFAP2C

homodimers:ESR1

Gene
ComplexR-HSA-8864384 (Reactome)
TFAP2A,TFAP2C homodimersComplexR-HSA-8864379 (Reactome)
TFAP2A-1 ProteinP05549-1 (Uniprot-TrEMBL)
TFAP2A-1 homodimerComplexR-HSA-8865818 (Reactome)
TFAP2A-1-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
TFAP2B homodimer:YEATS4ComplexR-HSA-8864598 (Reactome)
TFAP2B ProteinQ92481 (Uniprot-TrEMBL)
TFAP2B homodimerComplexR-HSA-8864596 (Reactome)
TFAP2B-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
TFAP2C homodimer:EGFR geneComplexR-HSA-8874796 (Reactome)
TFAP2C homodimer:MYC:KDM5B:CDKN1A geneComplexR-HSA-8865282 (Reactome)
TFAP2C homodimer:MYC:KDM5BComplexR-HSA-8865263 (Reactome)
TFAP2C ProteinQ92754 (Uniprot-TrEMBL)
TFAP2C homodimerComplexR-HSA-8864386 (Reactome)
TFAP2C-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
TFAP2C:WWOXComplexR-HSA-8864568 (Reactome)
TFAP2CProteinQ92754 (Uniprot-TrEMBL)
TFAP2D ProteinQ7Z6R9 (Uniprot-TrEMBL)
TFAP2E ProteinQ6VUC0 (Uniprot-TrEMBL)
TFAP2ComplexR-HSA-8864286 (Reactome)
TGFA Gene ProteinENSG00000163235 (Ensembl)
TGFA GeneGeneProductENSG00000163235 (Ensembl)
TGFA precursorProteinP01135 (Uniprot-TrEMBL)
UBE2I-G97-SUMO1 ProteinP63165 (Uniprot-TrEMBL)
UBE2IProteinP63279 (Uniprot-TrEMBL)
VEGFA gene ProteinENSG00000112715 (Ensembl)
VEGFA geneGeneProductENSG00000112715 (Ensembl)
VEGFAProteinP15692 (Uniprot-TrEMBL)
WWOX ProteinQ9NZC7 (Uniprot-TrEMBL)
WWOXProteinQ9NZC7 (Uniprot-TrEMBL)
YEATS4 ProteinO95619 (Uniprot-TrEMBL)
YEATS4ProteinO95619 (Uniprot-TrEMBL)
YY1 ProteinP25490 (Uniprot-TrEMBL)
YY1ProteinP25490 (Uniprot-TrEMBL)
atRAMetaboliteCHEBI:15367 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
APOE geneR-HSA-8869575 (Reactome)
APOE geneR-HSA-8869590 (Reactome)
APOEArrowR-HSA-8869590 (Reactome)
ATAD2:ESR1ArrowR-HSA-8937369 (Reactome)
ATAD2R-HSA-8937369 (Reactome)
CDKN1A geneR-HSA-8865244 (Reactome)
CDKN1A geneR-HSA-8865256 (Reactome)
CDKN1A geneR-HSA-8865280 (Reactome)
CDKN1AArrowR-HSA-8865256 (Reactome)
CGA GeneR-HSA-8864412 (Reactome)
CGA GeneR-HSA-8864433 (Reactome)
CGAArrowR-HSA-8864433 (Reactome)
CGAR-HSA-378978 (Reactome)
CGB3 GeneR-HSA-8864426 (Reactome)
CGB3 GeneR-HSA-8864431 (Reactome)
CGB3ArrowR-HSA-8864431 (Reactome)
CGB3R-HSA-378978 (Reactome)
CITED2,CITED4,(CITED1)R-HSA-8864307 (Reactome)
CREBBPR-HSA-8864307 (Reactome)
DEK:TFAP2A homodimer:APOE geneArrowR-HSA-8869575 (Reactome)
DEK:TFAP2A homodimer:APOE geneArrowR-HSA-8869590 (Reactome)
DEK:TFAP2A homodimerArrowR-HSA-8869580 (Reactome)
DEK:TFAP2A homodimerR-HSA-8869575 (Reactome)
DEKR-HSA-8869580 (Reactome)
EGFR geneR-HSA-8874789 (Reactome)
EGFR geneR-HSA-8874797 (Reactome)
EGFRArrowR-HSA-8874797 (Reactome)
EP300R-HSA-8864307 (Reactome)
ERBB2 GeneR-HSA-8864453 (Reactome)
ERBB2 GeneR-HSA-8864466 (Reactome)
ERBB2ArrowR-HSA-8864466 (Reactome)
ESR1 GeneR-HSA-8864381 (Reactome)
ESR1 GeneR-HSA-8864395 (Reactome)
ESR1ArrowR-HSA-8864395 (Reactome)
ESR1R-HSA-8937369 (Reactome)
GonadotropinArrowR-HSA-378978 (Reactome)
HSPD1 geneR-HSA-8869542 (Reactome)
HSPD1 geneR-HSA-8869558 (Reactome)
HSPD1ArrowR-HSA-8869558 (Reactome)
KCTD15R-HSA-8864361 (Reactome)
KCTD1R-HSA-8864343 (Reactome)
KDM5BR-HSA-8865265 (Reactome)
KIT GeneR-HSA-8864690 (Reactome)
KIT GeneR-HSA-8864698 (Reactome)
KITArrowR-HSA-8864698 (Reactome)
MYBL2 geneR-HSA-8869549 (Reactome)
MYBL2 geneR-HSA-8869566 (Reactome)
MYBL2ArrowR-HSA-8869566 (Reactome)
MYCR-HSA-8865265 (Reactome)
NOP2 geneR-HSA-8869543 (Reactome)
NOP2 geneR-HSA-8869560 (Reactome)
NOP2ArrowR-HSA-8869560 (Reactome)
NPM1:TFAP2A

homodimer:HSPD1

gene
ArrowR-HSA-8869542 (Reactome)
NPM1:TFAP2A

homodimer:HSPD1

gene
TBarR-HSA-8869558 (Reactome)
NPM1:TFAP2A

homodimer:MYBL2

gene
ArrowR-HSA-8869549 (Reactome)
NPM1:TFAP2A

homodimer:MYBL2

gene
TBarR-HSA-8869566 (Reactome)
NPM1:TFAP2A homodimer:NOP2 geneArrowR-HSA-8869543 (Reactome)
NPM1:TFAP2A homodimer:NOP2 geneTBarR-HSA-8869560 (Reactome)
NPM1:TFAP2A homodimerArrowR-HSA-8869568 (Reactome)
NPM1:TFAP2A homodimerR-HSA-8869542 (Reactome)
NPM1:TFAP2A homodimerR-HSA-8869543 (Reactome)
NPM1:TFAP2A homodimerR-HSA-8869549 (Reactome)
NPM1R-HSA-8869568 (Reactome)
PITX2 GeneR-HSA-8864718 (Reactome)
PITX2 GeneR-HSA-8864729 (Reactome)
PITX2ArrowR-HSA-8864729 (Reactome)
R-HSA-3234081 (Reactome) UBE2I (UBC9) interacts with TFAP2A, TFAP2B and TFAP2C, and the interaction site has been mapped to the C terminal region of TFAP2C; SUMOylation occurs on lysine-10 (Eloranta and Hurst 2002). As lysine-10 is conserved in TFAP2A and TFAP2B, SUMOylation of these factors is assumed to be on lysine-10 (Eloranta and Hurst 2002; Impens et al. 2014). SUMOylation causes a reduction in AP-2 transcriptional activation function but is required for its repressive function. A dominant negative mutant of UBC9 led to increased activation and reduced repressor function of TFAP2A and C, supporting the role of UBC9 in SUMOylation (Eloranta and Hurst 2002; Berlato et al. 2011). Isoform 1a of TFAP2A is SUMOylated, isoforms 1b and 1c lack lysine 10 and are not SUMOylated (Berlato et al. 2011). TFAP2D and TFAP2E lack lysine-10 and are thus assumed not to be SUMOylated. SUMOylation of TFAP2A blocked its ability to induce the expression of luminal genes and repression of basal genes (Bogachek et al. 2014). Disruption of the sumoylation pathway by knockdown of sumoylation enzymes, mutation of the SUMO-target lysine of TFAP2A, or treatment with sumoylation inhibitors induced MET in basal breast cancers, which was dependent on TFAP2A(Bogachek et al. 2014).
R-HSA-3234084 (Reactome) UBE2I (UBC9) interacts with the C terminal region of TFAP2B (Eloranta and Hurst 2002). As inferred from TFAP2C, SUMOylation of TFAP2B occurs at lysine in the VKYE motif and. therefore UBC9 is assumed to catalyze the ligation of SUMO1 to TFAP2B.
R-HSA-3234094 (Reactome) UBE2I (UBC9) interacts with the C-terminal region of TFAP2C (Eloranta and Hurst 2002). SUMOylation of TFAP2C occurs at lysine-10 and causes a reduction in its transcriptional activation activity. A dominant negative mutant of UBC9 led to increased activity of TFAP2C therefore UBC9 is assumed to catalyze the ligation of SUMO1 to TFAP2C.
R-HSA-378978 (Reactome) Human chorionic gonadotropin is a glycoprotein hormone produced in pregnancy. Its role is to maintain progesterone production by preventing the disintegration of the corpus luteum of the ovary and thus sustain the growing foetus (Rull & Laan 2005). Gonadotropin comprises an alpha subunit (CGA), common to the pituitary gonadotropin hormones (LH, FSH and TSH) and a distinct beta subunit (CGB3), unique for each hormone which confers receptor and biological specificity. The subunits are bound by six intrachain disulfide bonds, required for dimer formation (Beebe et al. 1990)
R-HSA-8864278 (Reactome) AP-2 family transcription factors (TFAP2) bind palindromic DNA response elements as dimers. AP-2 family members are able to form homo- and heterodimers through the interaction of their C-terminal helix-span-helix (HSH) motifs. Both HSH motifs and centrally located basic regions are needed for DNA binding (Williams and Tjian 1991a, Williams and Tjian 1991b).
R-HSA-8864307 (Reactome) Transcriptional co-factors from the CITED family interact with the helix-span-helix (HSH) domain of TFAP2 (AP-2) family of transcription factors and recruit transcription co-activators EP300 (p300) and CREBBP (CBP) to TFAP2-bound DNA elements. CITED2 shows the highest affinity for TFAP2 proteins, followed by CITED4, while CITED1 interacts with TFAP2s with a very low affinity. The interaction with CITED proteins was specifically demonstrated for TFAP2A (AP-2 alpha), TFAP2B (AP2-beta) and TFAP2C (AP-2 gamma), and is extrapolated to TFAP2D (AP2-delta) and TFAP2E (AP-2 epsilon) based on sequence similarity (Braganca et al. 2002, Braganca et al. 2003). Mouse embryos defective for CITED2 exhibit neural crest defects, cardiac malformations and adrenal agenesis, which can at least in part be attributed to defective Tfap2 transactivation (Bamforth et al. 2001).
R-HSA-8864343 (Reactome) The BTB domain at the N-terminus of KCTD1 binds to the N-terminal transactivation domain of TFAP2 (AP-2) family transcription factors. Binding of KCTD1 to TFAP2A, TFAP2B and TFAP2C inhibits their transcriptional activity, thus acting as a negative regulator (Ding et al. 2009). Based on sequence similarity, KCTD1 is assumed to interact with TFAP2D and TFAP2E.
R-HSA-8864361 (Reactome) KCTD15 binds to the transactivation domain of the TFAP2 (AP-2) family transcription factors and inhibits their transcriptional activity without affecting their protein levels, dimerization or nuclear localization. KCTD15-mediated inhibition of TFAP2 inhibits neural crest formation. KCTD15 interaction with TFAP2A was demonstrated using human and zebrafish proteins, while KCTD15 interaction with TFAP2B and TFAP2C is inferred from their ability to inhibit AP-2 reporter activity (Zarelli and Dawid 2013). Based on sequence similarity, it is assumed that TFAP2D and TFAP2E are candidate interaction partners of KCTD15.
R-HSA-8864381 (Reactome) AP-2 family transcription factors TFAP2A (AP-2 alpha) and TFAP2C (AP-2 gamma) bind to the TFAP2 consensus in the promoter of the estrogen receptor alpha (ESR1). It has not been tested whether heterodimers of TFAP2A and TFAP2C or only their respective homodimers can bind to the ESR1 promoter (McPherson and Weigel 1999). The presence of CITED proteins CITED2, CITED4 and CITED1, which act as TFAP2 co-activators, has not been examined at the ESR1 promoter but is plausible.
R-HSA-8864395 (Reactome) Binding of TFAP2A (AP-2 alpha) or TFAP2C (AP-2 gamma) dimers to the promoter of the estrogen receptor ESR1 gene promotes ESR1 transcription (McPherson and Weigel 1999). TFAP2A expression correlates with ESR1 expression in breast cancer and TFAP2C is frequently overexpressed in estrogen-positive breast cancer and endometrial cancer (deConinck et al. 1995, Turner et al. 1998).
R-HSA-8864412 (Reactome) The CGA (chorionic gonadotropin alpha) gene promoter contains several putative AP-2 transcription factor binding sites. TFAP2A (AP-2 alpha) and TFAP2C (AP-2 gamma), which are both expressed in the placenta, can both bind to the CGA promoter (Johnson et al. 1997, LiCalsi et al. 2000). It has not been examined whether TFAP2A and TFAP2C bind the CGA promoter as homodimers or heterodimers and if CITED family members are involved in TFAP2A/C-mediated transactivation of CGA transcription.
R-HSA-8864426 (Reactome) The CGB (chorionic gonadotropin beta) gene promoter, similar to CGA (chorionic gonadotropin alpha) gene promoter, contains several putative AP-2 transcription factor binding sites. TFAP2A (AP-2 alpha) and TFAP2C (AP-2 gamma), which are both expressed in the placenta, can both bind to the CGB promoter (Johnson et al. 1997, LiCalsi et al. 2000). It has not been examined whether TFAP2A and TFAP2C bind the CGB promoter as homodimers or heterodimers and if CITED family members are involved in TFAP2A/C-mediated transactivation of CGB transcription.
R-HSA-8864431 (Reactome) Homodimers of AP-2 family transcription factors TFAP2A (AP-2 alpha) and TFAP2C (AP-2 gamma) directly stimulate CGB (chorionic gonadotropin beta) transcription by binding to the CGB3 gene promoter (Johnson et al. 1997, LiCalsi et al. 2000).
R-HSA-8864433 (Reactome) Homodimers of AP-2 family transcription factors TFAP2A (AP-2 alpha) and TFAP2C (AP-2 gamma) directly stimulate CGA (chorionic gonadotropin alpha) transcription by binding to the CGA promoter (Johnson et al. 1997, LiCalsi et al. 2000).
R-HSA-8864453 (Reactome) Homodimers and heterodimers of AP-2 family transcription factors TFAP2A (AP-2 alpha), TFAP2B (AP-2 beta) and TFAP2C (AP-2 gamma) can bind to AP-2 response elements in the ERBB2 gene promoter (Bosher et al. 1996). TFAP2A forms a complex with YY1 (Ying Yang 1) transcription factor and recruits it to the ERBB2 promoter (Begon et al. 2005). Interaction of YY1 with TFAP2B and TFAP2C has not been examined but is plausible based on sequence similarity.
R-HSA-8864466 (Reactome) Binding of AP-2 transcription factors TFAP2A (AP-2 alpha), TFAP2B (AP-2 beta) and TFAP2C (AP-2 gamma) to AP-2 response elements in the ERBB2 gene promoter stimulates ERBB2 transcription, with TFAP2B having the weakest effect (Bosher et al. 1996). Association of YY1 transcription factor with TFAP2A (and, possibly, TFAP2B and TFAP2C) significantly increases the ERBB2 gene transcription rate (Begon et al. 2005).
R-HSA-8864569 (Reactome) The tumor suppressor WWOX associates with TFAP2C (AP-2 gamma) in the cytosol and prevents TFAP2C nuclear translocation and TFAP2C-mediated transcription. WWOX is also able to bind to TFAP2A, but the biological role of this interaction has not been examined (Aqeilan et al. 2004). Low levels of WWOX and high levels of TFAP2C are associated with tamoxifen resistance in breast cancer (Guler et al. 2007).
R-HSA-8864577 (Reactome) Like other AP-2 (TFAP2) transcription factor family members, TFAP2C (AP-2 gamma) mainly localizes to the nucleus. WWOX inhibits nuclear translocation of TFAP2C (Aqeilan et al. 2004).
R-HSA-8864595 (Reactome) TFAP2B (AP-2 beta) binds YEATS4 (GAS41). Formation of the TFAP2B:YEATS4 complex increases DNA binding and transcriptional activity of TFAP2B homodimers (Ding et al. 2006).
R-HSA-8864690 (Reactome) The gene encoding KIT receptor tyrosine kinase contains two AP-2 binding sites in its promoter. AP-2 (TFAP2) transcription factor family members TFAP2A (AP-2 alpha) and TFAP2B (AP-2 beta) can bind these sites most likely as homodimers (Huang et al. 1998). The role of TFAP2B in KIT gene regulation has been studied in less detail than the role of TFAP2A.
R-HSA-8864698 (Reactome) Binding of AP-2 alpha (TFAP2A) dimer to the KIT gene promoter stimulates KIT transcription. AP-2 beta (TFAP2B) may also stimulate KIT transcription. TFAP2A and KIT levels are frequently reduced in metastatic melanoma (Huang et al. 1998).
R-HSA-8864718 (Reactome) Homodimers of AP-2 transcription factor family members TFAP2A (AP-2 alpha) and TFAP2C (AP-2 gamma), in complex with CITED2, bind to the evolutionarily conserved AP-2 response elements in the promoter of the PITX2 gene (Bamforth et al. 2004, Li et al. 2012).
R-HSA-8864729 (Reactome) The PITX2 gene encodes a homeobox transcription factor involved in left-right patterning and heart development. The PITX2 gene expression is stimulated by binding of the complex of CITED2 and TFAP2A or TFAP2C homodimers to the AP-2 response elements in the PITX2 promoter (Bamforth et al. 2004, Li et al. 2012).
R-HSA-8864737 (Reactome) TFAP2A (AP-2 alpha) homodimer can associate with AP-2 response elements in the VEGFA gene promoter (Ruiz et al. 2004).
R-HSA-8864936 (Reactome) Binding of TFAP2A (AP-2 alpha) dimer to AP-2 response elements in the VEGFA gene promoter results in repression of VEGFA expression (Ruiz et al. 2004). CITED2, a transcription co-factor of TFAP2A, also represses VEGFA transcription, but the mechanism has not been established (Li et al. 2012).
R-HSA-8864989 (Reactome) TFAP2A (AP-2 alpha) transcription factor dimer binds an AP-2 response element in the promoter of the TGFA (transforming growth factor alpha) gene (Wang et al. 1997).
R-HSA-8864999 (Reactome) The TGFA gene encodes the precursor of the transforming growth factor alpha (TGF alpha). Binding of the TFAP2A homodimer to the promoter of the TGFA gene stimulates TGFA transcription (Wang et al. 1997).
R-HSA-8865244 (Reactome) TFAP2A (AP-2 alpha) transcription factor binds two AP-2 response elements in the promoter of the CDKN1A (p21) gene, the proximal site being TP53 (p53) independent, while the distal site is in the vicinity of the p53 response element (Zeng et al. 1997, Williams et al. 2009, Scibetta et al. 2010).
R-HSA-8865256 (Reactome) The CDKN1A gene encodes cyclin dependent kinase inhibitor also known as p21 or WAF1 which can induce G1 cell cycle arrest.

Binding of TFAP2A (AP-2 alpha) transcription factor to the CDKN1A promoter results in the activation of CDKN1A expression in a TP53 (p53) independent manner, which may be important during development and differentiation (Zeng et al. 1997, Williams et al. 2009, Scibetta et al. 2010).

Binding of TFAP2C (AP-2 gamma) transcription factor to the proximal AP-2 response element in the CDKN1A promoter (Scibetta et al. 2010) results in repression of CDKN1A transcription. TFAP2C may recruit histone deacetylases, such as HDAC2 to the CDKN1A promoter (Williams et al. 2009). TFAP2C cooperates with its interaction partners MYC and KDM5B in repression of the CDKN1A gene transcription. The mechanism may involve KDM5B-mediated removal of activating histone methylation mark at H3K4 from nucleosomes at the CDKN1A promoter. In the absence of TFAP2C, MYC can recruit KDM5B to the CDKN1A promoter via an AP-2 independent MYC-binding site, but this results in a lower level of CDKN1A gene repression. TFAP2C-mediated repression of CDKN1A transcription promotes G1/S transition (Wong et al. 2012). In contradiction, it has been reported that TFAP2C may induce, instead of repress CDKN1A transcription (Li et al. 2006).


R-HSA-8865265 (Reactome) TFAP2C (AP-2 gamma) transcription factor homodimer can form a complex with MYC transcription factor and histone demethylase KDM5B (Wong et al. 2012).
R-HSA-8865280 (Reactome) TFAP2C (AP-2 gamma) transcription factor, in cooperation with MYC and histone demethylase KDM5B binds the proximal AP-2 response element in the promoter of the CDKN1A (p21) gene (Williams et al. 2009, Scibetta et al. 2010, Wong et al. 2012).
R-HSA-8869542 (Reactome) In response to retinoic acid treatment, TFAP2A (AP-2 alpha) homodimers in complex with NPM1 (nucleophosmin) are recruited to the AP-2 alpha response element in the promoter of the mitochondrial chaperonin gene HSPD1 (Hsp60) (Liu et al. 2007).
R-HSA-8869543 (Reactome) In response to retinoic acid treatment, TFAP2A (AP-2 alpha) homodimers in complex with NPM1 (nucleophosmin) are recruited to the AP-2 alpha response element in the promoter of the nucleolar protein NOP2 (p120) (Liu et al. 2007).
R-HSA-8869549 (Reactome) In response to retinoic acid treatment, TFAP2A (AP-2 alpha) homodimers in complex with NPM1 (nucleophosmin) are recruited to the AP-2 alpha response element in the promoter of the transcription factor MYBL2 (b-Myb) (Liu et al. 2007).
R-HSA-8869558 (Reactome) In the course of retinoic acid-induced cell differentiation, formation of the complex between NPM1 (nucleophosmin) and TFAP2A (AP-2 alpha) homodimer, bound to the AP-2 alpha response element in the promoter of the HSPD1 (Hsp60) gene, represses transcription of the mitochondrial matrix chaperonin HSPD1. Transcriptional repression probably involves NPM1-mediated recruitment of histone deacetylases HDAC1 and HDAC2 to the HSPD1 gene promoter (Liu et al. 2007).
R-HSA-8869560 (Reactome) In the course of retinoic acid-induced cell differentiation, formation of the complex between NPM1 (nucleophosmin) and TFAP2A (AP-2 alpha) homodimer, bound to the AP-2 alpha response element in the promoter of the NOP2 (p120) gene, represses transcription of the nucleolar protein NOP2. Transcriptional repression probably involves NPM1-mediated recruitment of histone deacetylases HDAC1 and HDAC2 to the NOP2 gene promoter (Liu et al. 2007). NOP2 is a proliferation marker (Valdez et al. 1992).
R-HSA-8869566 (Reactome) In the course of retinoic acid-induced cell differentiation, formation of the complex between NPM1 (nucleophosmin) and TFAP2A (AP-2 alpha) homodimer, bound to the AP-2 alpha response element in the promoter of the MYBL2 (b-Myb) gene, represses transcription of the transcription factor MYBL2. Transcriptional repression probably involves NPM1-mediated recruitment of histone deacetylases HDAC1 and HDAC2 to the MYBL2 gene promoter (Liu et al. 2007). MYBL2 is involved in promotion of cellular proliferation (Saville and Watson 1998).
R-HSA-8869568 (Reactome) In response to retinoic acid treatment, NPM1 (nucleophosmin) forms a complex with the TFAP2A (AP-2 alpha) homodimer (Liu et al. 2007).
R-HSA-8869575 (Reactome) DEK is recruited to the APOE gene promoter via its interaction with the TFAP2A (AP-2 alpha) homodimer. In the presence of DEK, TFAP2A associates with the APOE promoter more tightly (Campillos et al. 2003). Binding of TFAP2A to the APOE gene promoter may be stimulated by PKA-mediated phosphorylation of TFAP2A (Garcia et al. 1999).
R-HSA-8869580 (Reactome) DEK forms a complex with TFAP2A homodimers (Campillos et al. 2003).
R-HSA-8869590 (Reactome) The complex of TFAP2A homodimer and DEK stimulates transcription of the APOE gene (Campillos et al. 2003).
R-HSA-8874789 (Reactome) TFAP2C (AP-2 gamma) homodimer binds the promoter region of the EGFR gene (Park et al. 2015, De Andrade et al. 2016).
R-HSA-8874797 (Reactome) Binding of TFAP2C homodimers to the EGFR gene promoter region stimulates EGFR transcription and may play an important role in the etiology of luminal breast cancer (Park et al. 2015, de Andrade et al. 2016).
R-HSA-8937369 (Reactome) ATPase family AAA domain-containing protein 2 (ATAD2 aka ANCCA) is a highly conserved protein primarily located in the cell nucleus. Its protein structure consists of two AAA domains and one bromodomain, indicating roles related to genome regulation, such as acting on chromatin structure and function (Caron et al. 2010, Magnani & Lupien 2014). ATAD2 is highly expressed in multiple cancers (Krakstad et al. 2015, Ciro et al. 2009, ) and is a strong predictor of rapid mortality in lung and breast cancers sufferers (Caron et al. 2010). Additionally, ATAD2 functions as a co-activator of the estrogen receptor (ESR1) and the androgen receptor (Zou et al. 2009), implicating it as an oncogenic protein in hormone-related cancers such as breast cancer and prostate cancer (Zou et al. 2007). This reaction shows ATAD2 binding to ESR1.
SUMO1:C93-UBE2IR-HSA-3234081 (Reactome)
SUMO1:C93-UBE2IR-HSA-3234084 (Reactome)
SUMO1:C93-UBE2IR-HSA-3234094 (Reactome)
SUMO1:C93-UBE2Imim-catalysisR-HSA-3234081 (Reactome)
SUMO1:C93-UBE2Imim-catalysisR-HSA-3234084 (Reactome)
SUMO1:C93-UBE2Imim-catalysisR-HSA-3234094 (Reactome)
SUMO1:TFAP2A-1 homodimerArrowR-HSA-3234081 (Reactome)
SUMO1:TFAP2B homodimerArrowR-HSA-3234084 (Reactome)
SUMO1:TFAP2C homodimerArrowR-HSA-3234094 (Reactome)
TFAP2

homo- and

heterodimers:CITED2,CITED4,(CITED1):EP300:CREBBP
ArrowR-HSA-8864307 (Reactome)
TFAP2 homo- and heterodimers:KCTD15ArrowR-HSA-8864361 (Reactome)
TFAP2 homo- and heterodimers:KCTD1ArrowR-HSA-8864343 (Reactome)
TFAP2 homo- and heterodimersArrowR-HSA-8864278 (Reactome)
TFAP2 homo- and heterodimersR-HSA-8864307 (Reactome)
TFAP2 homo- and heterodimersR-HSA-8864343 (Reactome)
TFAP2 homo- and heterodimersR-HSA-8864361 (Reactome)
TFAP2A

homodimer:CDKN1A

gene
ArrowR-HSA-8865244 (Reactome)
TFAP2A

homodimer:CDKN1A

gene
ArrowR-HSA-8865256 (Reactome)
TFAP2A homodimer:TGFA geneArrowR-HSA-8864989 (Reactome)
TFAP2A homodimer:TGFA geneArrowR-HSA-8864999 (Reactome)
TFAP2A

homodimer:VEGFA

Gene
ArrowR-HSA-8864737 (Reactome)
TFAP2A

homodimer:VEGFA

Gene
TBarR-HSA-8864936 (Reactome)
TFAP2A homodimerR-HSA-8864737 (Reactome)
TFAP2A homodimerR-HSA-8864989 (Reactome)
TFAP2A homodimerR-HSA-8865244 (Reactome)
TFAP2A homodimerR-HSA-8869568 (Reactome)
TFAP2A homodimerR-HSA-8869580 (Reactome)
TFAP2A,(TFAP2B) homodimers:KIT geneArrowR-HSA-8864690 (Reactome)
TFAP2A,(TFAP2B) homodimers:KIT geneArrowR-HSA-8864698 (Reactome)
TFAP2A,(TFAP2B) homodimersR-HSA-8864690 (Reactome)
TFAP2A,(TFAP2B,TFAP2C) homo- and heterodimers:YY1:ERBB2 geneArrowR-HSA-8864453 (Reactome)
TFAP2A,(TFAP2B,TFAP2C) homo- and heterodimers:YY1:ERBB2 geneArrowR-HSA-8864466 (Reactome)
TFAP2A,(TFAP2B,TFAP2C) homo- and heterodimersR-HSA-8864453 (Reactome)
TFAP2A,TFAP2C homodimers:CGA GeneArrowR-HSA-8864412 (Reactome)
TFAP2A,TFAP2C homodimers:CGA GeneArrowR-HSA-8864433 (Reactome)
TFAP2A,TFAP2C homodimers:CGB geneArrowR-HSA-8864426 (Reactome)
TFAP2A,TFAP2C homodimers:CGB geneArrowR-HSA-8864431 (Reactome)
TFAP2A,TFAP2C homodimers:CITED2:PITX2 GeneArrowR-HSA-8864718 (Reactome)
TFAP2A,TFAP2C homodimers:CITED2:PITX2 GeneArrowR-HSA-8864729 (Reactome)
TFAP2A,TFAP2C homodimers:CITED2R-HSA-8864718 (Reactome)
TFAP2A,TFAP2C

homodimers:ESR1

Gene
ArrowR-HSA-8864381 (Reactome)
TFAP2A,TFAP2C

homodimers:ESR1

Gene
ArrowR-HSA-8864395 (Reactome)
TFAP2A,TFAP2C homodimersR-HSA-8864381 (Reactome)
TFAP2A,TFAP2C homodimersR-HSA-8864412 (Reactome)
TFAP2A,TFAP2C homodimersR-HSA-8864426 (Reactome)
TFAP2A-1 homodimerR-HSA-3234081 (Reactome)
TFAP2B homodimer:YEATS4ArrowR-HSA-8864595 (Reactome)
TFAP2B homodimerR-HSA-3234084 (Reactome)
TFAP2B homodimerR-HSA-8864595 (Reactome)
TFAP2C homodimer:EGFR geneArrowR-HSA-8874789 (Reactome)
TFAP2C homodimer:EGFR geneArrowR-HSA-8874797 (Reactome)
TFAP2C homodimer:MYC:KDM5B:CDKN1A geneArrowR-HSA-8865280 (Reactome)
TFAP2C homodimer:MYC:KDM5B:CDKN1A geneTBarR-HSA-8865256 (Reactome)
TFAP2C homodimer:MYC:KDM5BArrowR-HSA-8865265 (Reactome)
TFAP2C homodimer:MYC:KDM5BR-HSA-8865280 (Reactome)
TFAP2C homodimerR-HSA-3234094 (Reactome)
TFAP2C homodimerR-HSA-8865265 (Reactome)
TFAP2C homodimerR-HSA-8874789 (Reactome)
TFAP2C:WWOXArrowR-HSA-8864569 (Reactome)
TFAP2C:WWOXTBarR-HSA-8864577 (Reactome)
TFAP2CArrowR-HSA-8864577 (Reactome)
TFAP2CR-HSA-8864569 (Reactome)
TFAP2CR-HSA-8864577 (Reactome)
TFAP2R-HSA-8864278 (Reactome)
TGFA GeneR-HSA-8864989 (Reactome)
TGFA GeneR-HSA-8864999 (Reactome)
TGFA precursorArrowR-HSA-8864999 (Reactome)
UBE2IArrowR-HSA-3234081 (Reactome)
UBE2IArrowR-HSA-3234084 (Reactome)
UBE2IArrowR-HSA-3234094 (Reactome)
VEGFA geneR-HSA-8864737 (Reactome)
VEGFA geneR-HSA-8864936 (Reactome)
VEGFAArrowR-HSA-8864936 (Reactome)
WWOXR-HSA-8864569 (Reactome)
YEATS4R-HSA-8864595 (Reactome)
YY1R-HSA-8864453 (Reactome)
atRAArrowR-HSA-8869568 (Reactome)

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