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Gene Review

TfAP-2  -  Transcription factor AP-2

Drosophila melanogaster

Synonyms: AP-2, AP-2alpha, CG7807, DAP-2, Dmel\CG7807, ...
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Disease relevance of AP-2


High impact information on AP-2

  • The deduced primary amino acid sequence of AP-2 does not contain a domain resembling any previously identified DNA binding motif [2].
  • Transfection of cDNA clones into Drosophila cells indicates that the AP-2 gene product can also activate gene expression in vivo in a DNA template-dependent manner [2].
  • Here, we report the isolation and characterization of a human cDNA clone containing the entire protein-coding region of AP-2 [2].
  • Expression of the AP-2 clone in bacteria yields a protein that binds to DNA and activates transcription in vitro in a comparable manner to native human AP-2 [2].
  • However, an interesting feature of the AP-2 protein is a clustered arrangement of proline and glutamine residues that have been found recently within the activation domains of other transcription factors [2].

Biological context of AP-2


Anatomical context of AP-2

  • Overexpression of GFP-stonin 2 interferes with recruitment of AP-2 to the plasma membrane and impairs internalization of the transferrin, epidermal growth factor, and low density lipoprotein receptors [7].
  • The adaptor protein (AP) complexes AP-1, AP-2, and AP-3 mediate coated vesicle formation and sorting of integral membrane proteins in the endocytic and late exocytic pathways in mammalian cells [8].
  • DAP-2 is expressed in discrete regions of procephalic neuroectoderm, the brain, ventral nerve cord, and maxillary segment during Drosophila embryogenesis, and in the brain, optic lobes, ventral nerve cord, antenno-maxillary complex, and antennal and leg imaginal disks in third instar larvae [9].
  • Both Stoned proteins colocalize precisely with endocytotic proteins including the AP2 complex and Dynamin in the "lattice network" characteristic of endocytotic domains in Drosophila presynaptic terminals [10].
  • In parallel with recent biochemical studies, this genetic analysis strongly suggests that Stoned proteins regulate the AP2-Synaptotagmin I interaction during synaptic vesicle endocytosis [10].

Other interactions of AP-2

  • The AP-2 family of transcription factors (AP-2alpha, AP-2beta and AP-2gamma) is temporally and spatially regulated in mammals and has also been implicated in oncogenesis [5].
  • Sequences encoding the InR, DPE, AP-2, and Sp1 sites were 100% conserved between human and murine KCC1 genes [6].

Analytical, diagnostic and therapeutic context of AP-2

  • Whole-mount in situ hybridizations demonstrated that DAP-2 is expressed initially at stage 9 of Drosophila embryonic development and that DAP-2 transcripts are detected in regions of the brain, eye-antennal disc, optical lobe, antenno-maxillary complex, and in a subset of cells of the ventral nerve cord [5].


  1. The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. Qin, H., Sun, Y., Benveniste, E.N. J. Biol. Chem. (1999) [Pubmed]
  2. Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements. Williams, T., Admon, A., Lüscher, B., Tjian, R. Genes Dev. (1988) [Pubmed]
  3. The AP-2 transcription factor is required for joint formation and cell survival in Drosophila leg development. Kerber, B., Monge, I., Mueller, M., Mitchell, P.J., Cohen, S.M. Development (2001) [Pubmed]
  4. Drosophila transcription factor AP-2 in proboscis, leg and brain central complex development. Monge, I., Krishnamurthy, R., Sims, D., Hirth, F., Spengler, M., Kammermeier, L., Reichert, H., Mitchell, P.J. Development (2001) [Pubmed]
  5. Cloning and characterization of the Drosophila homologue of the AP-2 transcription factor. Bauer, R., McGuffin, M.E., Mattox, W., Tainsky, M.A. Oncogene (1998) [Pubmed]
  6. Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2 and contains a functional downstream promoter element. Zhou, G.P., Wong, C., Su, R., Crable, S.C., Anderson, K.P., Gallagher, P.G. Blood (2004) [Pubmed]
  7. Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery. Martina, J.A., Bonangelino, C.J., Aguilar, R.C., Bonifacino, J.S. J. Cell Biol. (2001) [Pubmed]
  8. Defective expression of the mu3 subunit of the AP-3 adaptor complex in the Drosophila pigmentation mutant carmine. Mullins, C., Hartnell, L.M., Wassarman, D.A., Bonifacino, J.S. Mol. Gen. Genet. (1999) [Pubmed]
  9. DAP-2, the Drosophila homolog of transcription factor AP-2. Monge, I., Mitchell, P.J. Mech. Dev. (1998) [Pubmed]
  10. Interaction of stoned and synaptotagmin in synaptic vesicle endocytosis. Fergestad, T., Broadie, K. J. Neurosci. (2001) [Pubmed]
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