The gene encompasses 22.882 kb of DNA; 7 exons.

mRNA, NM_001042425; NM_003220; NM_001032280.

The main TFAP2A isoform consists of 437 amino acids and has a molecular weight of 52 kDa. TFAP2A proteins contain a unique, highly conserved helix-span-helix dimerization motif at the C-terminal half of the protein, a central basic region and a less conserved proline- and glutamine-rich domain at the amino terminus. The helix-span-helix motif and the basic region mediate DNA binding and dimerization while the proline- and glutamine-rich region is responsible for transcriptional transactivation (see figure 3).

Ubiquitous. Abnormal expression is found in a variety of human tumours.

Located predominantly in the nucleus.

The TFAP2A proteins are able to form hetero- as well as homo-dimers and bind to GC-rich DNA sequences within regulatory regions of their target genes, mediating both activation and repression of gene transcription. Functional TFAP2 binding sites, such as 5-GCCN3GGC-3 or 5-GCCN4GGC-3 or 5-GCCN3/4GGG-3 or 5-CCCCAGGC-3 have been identified and regulate genes involved in physiological or pathological processes such as development, cell growth, differentiation, apoptosis and tumorigenesis. Examples of activated genes are CDKN1A, TGFA, estrogen receptor, keratinocyte-specific genes, KIT, ERBB2 and IGFBP5 while MCAM/MUC18, C/EBPA, MYC and DCBLD2/ESDN/CLCP1 are repressed by TFAP2A. TFAP2A protein expression is highly cell-type specific, showing different spatial and temporal expression during development and in various tissues. The TFAP2A proteins are essential during embryogenesis as demonstrated by mouse genetic studies. Loss of TFAP2A impairs cranial closure and leads to severe dismorphogenesis of different organs and death at birth. Loss of TFAP2A activity in general alters proliferation and induces premature differentiation and/or apoptosis in various cell types as demonstrated by in vivo and in vitro studies. Because of their involvement in these fundamental cellular processes TFAP2A proteins are essential for maintaining cellular homeostasis. Deregulation of TFAP2A protein levels alter the cell functions in such a drastic way that it can eventually lead to cancer formation and/or progression. In fact, several studies have associated aberrant TFAP2A activity with tumorigenesis (see below).

With the other members of the TFAP2 family: TFAP2B, TFAP2C, TFAP2D, TFAP2E.

Found in branchio-oculo-facial syndrome (BOFS).
A de novo 10529A-G transition in exon 4 of the TFAP2A human gene was found in an 18-year-old man with branchio-oculo-facial syndrome (BOFS), a rare autosomal-dominant cleft palate-craniofacial disorder with variable expressivity. The mutation leads to arg255-to-gly (R255G) substitution in a highly conserved residue in the basic region of the DNA-binding domain, a change that replaces a charged polar side chain with a nonpolar side chain with a predicted conformational space change. Four additional BOFS patients were found to have de novo missense mutations in the highly conserved exons 4 and 5. No mutations were found in more than 300 controls. (Milunsky et al., 2008).
A de novo deletion of 18 and insertion of 6 nucleotides, resulting in LPGARR deletion and RI insertion between amino acids 276 and 281, was found within the basic DNA binding and dimerization domains of TFAP2A in a 4-year-old girl with congenital sensorineural deafness associated with inner ear malformation. The girl also had pseudocleft lips, skin defects, auricle abnormalities, and unilateral multicystic dysplastic kidney, leading to the diagnosis of branchio-oculo-facial (BOF) syndrome. (Tekin et al., 2009).