Protein Domain : Transcription factor AP-2 alpha, N-terminal IPR008121

Type	Domain
Description	Activator protein-2 (AP-2) transcription factors constitute a family of closely related and evolutionarily conserved proteins that bind to the DNA consensus sequence 5'-GCCNNNGGC-3' and stimulate target gene transcription [, ]. Five different isoforms of AP-2 have been identified in mammals, termed AP-2 alpha, beta, gamma, delta and epsilon. Each family member shares a common structure, possessing a proline/glutamine-rich domain in the N-terminal region, which is responsible for transcriptional activation [], and a helix-span-helix domain in the C-terminal region, which mediates dimerisation and site-specific DNA binding [].The AP-2 family have been shown to be critical regulators of gene expression during embryogenesis. They regulate the development of facial prominence and limb buds, and are essential for cranial closure and development of the lens [ , ]; they have also been implicated in tumorigenesis. AP-2 protein expression levels have been found to affect cell transformation, tumour growth and metastasis, and may predict survival in some types of cancer [, ]. Mutations in human AP-2 have been linked with bronchio-occular-facial syndrome and Char Syndrome, congenital birth defects characterised by craniofacial deformities and patent ductus arteriosus, respectively []. AP-2 alpha was initially isolated from human HeLa cells [ ]. The protein wasshown to bind to enhancer regions of the SV40 and human metallothionein IIA promoters, and to stimulate RNA synthesis []. AP-2 alpha gene knockout in mice causes neural-tube defects during embryogenesis, leading to craniofacial abnormalities and anencephaly []. In humans, deletion of chromosome 6region 6p24-p25, which includes the AP-2 alpha gene, is associated with microphthalmia, corneal clouding and a number of other dysmorphic features, including hypertelorism, micrognathia, dysplastic ears, thin limbs, and congenital cardiac defects.This entry represents the N-terminal region of these proteins, including the transcriptional activation domain.
Short Name	TF_AP2_alpha_N