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FLASH GENE

Symbol

TFAP2A

contributors: mct/npt/pgu - updated : 24-04-2019

HGNC name	transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha)
HGNC id	11742

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	22.88 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D6S1713 - D6S477 - D6S1640 - DSP - BMP6 - D6S1674 - D6S309 - D6S297 - D6S263 - D6S296 - D6S410 - D6S1574 - D6S470 - TFAP2A - CAPZB2 - GCNT2 - EDN1 - D6S1446 - D6S1034 - cen

RNA

TRANSCRIPTS	type	messenger

text	four alternative forms

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003220 7 - 3300 48 437 - 2009 19115315 NM_001032280 7 - 3808 - 431 - 1992 1587861 NM_001042425 7 - 3150 - 433 - 1992 1587861 TFAP2AN - - - - 165 - 2009 19115315 TFAP2AC - - - - 263 - 2009 19115315

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Reproductive female system uterus cervix   highly   female system breast mammary gland   highly   female system placenta     highly Visual eye       highly Mus musculus Fetal

cells

System Cell Pubmed Species Stage Rna symbol not specific chondrocyte Visual amacrine cell Mus musculus Fetal Visual horizontal association cell Mus musculus Fetal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

Text	neural tube
	expressed by 14 weeks gestation and by 22 weeks its expression becomes restricted to the luminal epithelial cells
	expressed in the ventral non-neural ectoderm

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal transactivation domain
	a complex DNA binding and dimerization motif
	a WW-binding motif mediating interaction with WWOX
	a C-terminal helix-span-helix motif mediating dimerization

mono polymer

homomer , heteromer , dimer

HOMOLOGY

interspecies

homolog to murine Tcfap2a

Homologene

FAMILY

AP2 family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus
text	completely co-localized with KCTD1 in the nuclei of cells

basic FUNCTION	transcription activator, regulating the expression of genes required for development of tissues of ectodermal origin
	cellular proteins that drive the polymerization of clathrin triskelia into cage structures
	activating CDKN1A (WAF1) and other genes such as MCAM
	retinoic-acid-responsive gene potentially involved in anterior eye chamber development
	TFAP2A is a ubiquitously present transcription factor that has been recently reported to be essential for cardiomyocyte viability and involved in congenital heart diseases
	playing a negative role in chondrocyte differentiation
	required for normal development of multiple structures during embryogenesis, including the face and limbs
	with TFAP2C, play an essential role in tumorigenesis
	a specific fraction of the TFAP2A-derived endocytic pathway is dedicated to secretory purposes under the control of AP1 and AP1AR
	involved in regulating mid-face development and upper lip fusion
	TFAP2A and FOXD3, in addition to their respective roles in the differentiation of neural crest derivatives, also jointly maintain the balance of BMP and WNT signaling in order to delineate the neural crest induction domain (
	IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues 3)
	duplicated in the chordate lineage and is essential for development of the neural crest

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

TFAP2A-IRF6-GRHL3 genetic pathway is shared by two embryologically distinct morphogenetic events that previously were considered independent during mammalian development

a component	binds DNA as a dimer
	can form homodimers or heterodimers with other AP-2 family members

INTERACTION

DNA	sequence specific DNA binding

RNA

small molecule

protein	Eps15 (EDH5) for receptor-mediated endocytosis
	interacts with WWOX and with CITED4
	associating with AAK1 (phosphorylates the micro2 subunit of TFAP2A and regulates its recruitment to tyrosine-based internalization motifs found on membrane-bound receptors)
	interacting with KCTD1 (significantly repressed TFAP2-mediated transactivation through the BTB domain)
	essential role for TFAP2A in MUC8 gene expression
	binds CDKN1A to two regions of the promoter: the proximal region where the AP-2 site lies and upstream near the major TP53 binding site
	plays a negative role in regulating CHRNA7 transcription
	possible interaction between FOXD1 and TFAP2A
	in neural crest cells TFAP2A directly activates expression of SOX10, which encodes a transcription factor essential for neural crest development
	synergistic effects of HRK promoter hypermethylation and loss of TFAP2A transactivation lead to HRK gene silencing and confer resistance to apoptosis and enhanced tumor growth
	CAPN7 interacted with activator protein 2 (TFAP2A), an important transcription factor of MMP2
	MYO6 functions in endocytosis in conjunction with binding partners including adaptor protein (TFAP2A, DAB2, and GIPC1)
	TFAP2A regulates activated F2R signaling by altering receptor surface expression and through recruitment of regulator of G protein signaling (RGS) proteins
	IRF6 regulates TFAP2A protein level in epidermal development 3)

cell & other

binding of TFAP2A adaptor complex to brain membrane is regulated by phosphorylation of proteins

REGULATION

induced by

retinoic acid

Other

developmentally regulated

ASSOCIATED DISORDERS

corresponding disease(s)

DEL6PD , BOFS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in tumor growth and metastasis of melanoma cells tumoral     --over   strongly expressed in poorly differentiated neuroblastomas constitutional     --low   accompanied by altered patterning of the forelimb, resulting in postaxial polydactyly

Susceptibility

potentially susceptibility gene for spina-bifida to Orofacial clefts

Variant & Polymorphism SNP	1257C
	de novo mutations in IRF6, TFAP2A, and ZFHX4 are associated with Orofacial clefts

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS