Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 6 (13), 246

The AP-2 Family of Transcription Factors


The AP-2 Family of Transcription Factors

Dawid Eckert et al. Genome Biol.


The AP-2 family of transcription factors consists of five different proteins in humans and mice: AP-2alpha, AP-2beta, AP-2gamma, AP-2delta and AP-2epsilon. Frogs and fish have known orthologs of some but not all of these proteins, and homologs of the family are also found in protochordates, insects and nematodes. The proteins have a characteristic helix-span-helix motif at the carboxyl terminus, which, together with a central basic region, mediates dimerization and DNA binding. The amino terminus contains the transactivation domain. AP-2 proteins are first expressed in primitive ectoderm of invertebrates and vertebrates; in vertebrates, they are also expressed in the emerging neural-crest cells, and AP-2alpha-/- animals have impairments in neural-crest-derived facial structures. AP-2beta is indispensable for kidney development and AP-2gamma is necessary for the formation of trophectoderm cells shortly after implantation; AP-2alpha and AP-2gamma levels are elevated in human mammary carcinoma and seminoma. The general functions of the family appear to be the cell-type-specific stimulation of proliferation and the suppression of terminal differentiation during embryonic development.


Figure 1
Figure 1
Phylogenetic tree of the AP-2 family. Amino-acid sequence alignments were performed using ClustalW implemented in Sequence Data Explorer of the MEGA3 software [67]. The phylogenetic tree was created using the neighbor-joining method (gaps setting: pairwise deletion; distance method: number of differences). Numbers at selected nodes indicate the percentage frequencies of branch association on the basis of 1,000 bootstrap repetitions. The scale bar indicates the number of residue changes. Asterisks indicate predicted proteins; brackets denote subfamilies in vertebrates. Species: Caenorhabditis elegans (nematode); Ciona intestinalis (sea squirt); Drosophila melanogaster (fruit fly); Danio rerio (zebrafish); Gallus gallus (chicken); Homo sapiens (human); Mus musculus (mouse); Pan troglodytes (chimpanzee); Rattus norvegicus (rat); Xenopus laevis and Xenopus tropicalis (frog).
Figure 2
Figure 2
A schematic representation of the protein structure of an AP-2α dimer, showing the proline- and glutamine (P/Q)-rich transactivation domain (89 amino acids, red), the PY motif within this domain (5 amino acids, green), the basic domain (20 amino acids, yellow) and the helix-span-helix motif (131 amino acids, blue). The helix-span-helix motif is responsible for dimerization of the proteins and mediates DNA binding together with the basic domain. Modified from SwissProt, ID: P34056 [68].

Similar articles

See all similar articles

Cited by 153 articles

See all "Cited by" articles


    1. Hilger-Eversheim K, Moser M, Schorle H, Buettner R. Regulatory roles of AP-2 transcription factors in vertebrate development, apoptosis and cell-cycle control. Gene. 2000;260:1–12. doi: 10.1016/S0378-1119(00)00454-6. - DOI - PubMed
    1. Zhao F, Satoda M, Licht JD, Hayashizaki Y, Gelb BD. Cloning and characterization of a novel mouse AP-2 transcription factor, AP-2delta, with unique DNA binding and transactivation properties. J Biol Chem. 2001;276:40755–40760. doi: 10.1074/jbc.M106284200. - DOI - PubMed
    1. Wang HV, Vaupel K, Buettner R, Bosserhoff AK, Moser M. Identification and embryonic expression of a new AP-2 transcription factor, AP-2 epsilon. Dev Dyn. 2004;231:128–135. doi: 10.1002/dvdy.20119. - DOI - PubMed
    1. Feng W, Williams T. Cloning and characterization of the mouse AP-2 epsilon gene: a novel family member expressed in the developing olfactory bulb. Mol Cell Neurosci. 2003;24:460–475. doi: 10.1016/S1044-7431(03)00209-4. - DOI - PubMed
    1. IMCB - Fugu Genome Project

Publication types


LinkOut - more resources