Contents

TFAP2A

Protein-coding gene in the species Homo sapiens

TFAP2A
Identifiers
Aliases	TFAP2A, AP-2, AP-2alpha, AP2TF, BOFS, TFAP2, transcription factor AP-2 alpha
External IDs	OMIM: 107580; MGI: 104671; HomoloGene: 2421; GeneCards: TFAP2A; OMA:TFAP2A - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p24.3 Start 10,393,186 bp[1] End 10,419,659 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 A3.3|13 20.01 cM Start 40,868,778 bp[2] End 40,891,852 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of thigh gingival epithelium skin of arm vulva skin of hip skin of abdomen hair follicle epithelium of lactiferous gland lactiferous duct nipple Top expressed in hair follicle epithelium of lens conjunctival fornix lip cornea lobe of prostate skin of abdomen parotid gland skin of external ear maxillary prominence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein dimerization activity protein homodimerization activity DNA-binding transcription factor activity transcription coactivator activity DNA-binding transcription activator activity, RNA polymerase II-specific chromatin binding cis-regulatory region sequence-specific DNA binding transcription cis-regulatory region binding RNA polymerase II cis-regulatory region sequence-specific DNA binding transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding DNA-binding transcription repressor activity, RNA polymerase II-specific protein binding RNA polymerase II core promoter sequence-specific DNA binding sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific RNA polymerase II transcription regulatory region sequence-specific DNA binding Cellular component centrosome Golgi apparatus intracellular membrane-bounded organelle nucleus nucleoplasm cytosol Biological process roof of mouth development cellular response to iron ion regulation of transcription, DNA-templated retina layer formation kidney development positive regulation of bone mineralization trigeminal nerve development negative regulation of transcription by competitive promoter binding optic vesicle morphogenesis bone morphogenesis negative regulation of apoptotic process hearing eyelid development in camera-type eye transcription, DNA-templated positive regulation of transcription, DNA-templated positive regulation of neuron apoptotic process positive regulation of gene expression inner ear morphogenesis optic cup structural organization regulation of cell differentiation embryonic cranial skeleton morphogenesis negative regulation of reactive oxygen species metabolic process negative regulation of transcription, DNA-templated embryonic forelimb morphogenesis oculomotor nerve formation negative regulation of cell population proliferation positive regulation of tooth mineralization transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II positive regulation of nucleic acid-templated transcription Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7020 21418 Ensembl ENSG00000137203 ENSMUSG00000021359 UniProt P05549 P34056 RefSeq (mRNA) NM_001032280 NM_001042425 NM_003220 NM_001372066 NM_001122948 NM_001301674 NM_011547 RefSeq (protein) NP_001027451 NP_001035890 NP_003211 NP_001358995 NP_001116420 NP_001288603 NP_035677 Location (UCSC) Chr 6: 10.39 – 10.42 Mb Chr 13: 40.87 – 40.89 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transcription factor AP-2 alpha (Activating enhancer binding Protein 2 alpha), also known as TFAP2A, is a protein that in humans is encoded by the TFAP2A gene.^[5]

Function[edit]

Transcription factor AP-2 alpha is a 52-kD sequence-specific DNA-binding protein that enhances transcription of specific genes by binding to a GC-rich DNA sequence first identified in the cis-regulatory region of SV40 virus DNA and in cis-regulatory regions of a variety of cellular genes.^[6]

The TFAP2-alpha gene was isolated and found to be retinoic acid-inducible in NT2 teratocarcinoma cells suggesting a potential role for AP-2 alpha in cellular differentiation.^{[7][8] [9]}

During embryonic development, AP-2 alpha is expressed in neural crest cells migrating from the cranial neural folds during neural tube closure, and is also expressed in ectoderm, parts of the central nervous system, limb buds, and mesonephric system suggesting that AP-2 alpha plays an important role in the determination and development of these tissues.^[10] Cranial neural crest cells populate the developing face and provide patterning information for craniofacial morphogenesis and generate most of the skull bones and the cranial ganglia.^[11]

AP-2 alpha knockout mice die perinatally with cranio-abdominoschisis and severe dysmorphogenesis of the face, skull, sensory organs, and cranial ganglia.^[12] Homozygous knockout mice also have neural tube defects followed by craniofacial and body wall abnormalities.^[13] In vivo gene delivery of AP-2 alpha suppressed spontaneous intestinal polyps in the Apc(Min/+) mouse.^[14] AP-2 alpha also functions as a master regulator of multiple transcription factors in the mouse liver.^[15]

Inmelanocytic cells TFAP2A gene expression may be regulated by MITF.^[16]

Clinical significance[edit]

Mutations in the TFAP2A gene cause Branchio-oculo-facial syndrome often with a midline cleft lip.^[17] In a family with branchio-oculo-facial syndrome (BOFS),^[18] a 3.2-Mb deletion at chromosome 6p24.3 was detected.^[19] Sequencing of candidate genes in that region in 4 additional unrelated BOFS patients revealed 4 different de novo missense mutations in the exons 4 and 5 of the TFAP2A gene.

A disruption of an AP-2 alpha binding site in an IRF6 enhancer is associated with cleft lip.^[20] Mutations in IRF6 gene cause Van der Woude syndrome (VWS)^[21] that is a rare mendelian clefting autossomal dominant disorder with lower lip pits in 85% of affected individuals.^[22] The remaining 15% of individuals with Van der Woude syndrome show only cleft lip and/or cleft palate (CL/P) and are clinically indistinguishable from the common non syndromic CL/P. NSCL/P occur in approximately 1/700 live births and is one of the most common form of congenital abnormalities. A previous association study between SNPs in and around IRF6 and NSCL/P have shown significant results in different populations^[23] and was independently replicated.^{[24][25][26][27]}

A search of NSCL/P cases for potential regulatory elements for IRF6 gene was made aligning genomic sequences to a 500 Kb region encompassing IRF6 from 17 vertebrate species. Human sequence as reference and searched for multispecies conserved sequences (MCSs). Regions contained in introns 5’ and 3’ flanking IRF6 were screened by direct sequencing for potential causative variants in 184 NSCL/P cases. The rare allele of the SNP rs642961 showed a significant association with cleft lip cases. Analysis of transcription factor binding site analysis showed that the risk allele disrupt a binding site for AP-2 alpha.^[20]

Mutations in the AP-2 alpha gene also cause branchio-oculo-facial syndrome,^[19] which has overlapping features with Van der Woude syndrome such as orofacial clefting and occasional lip pits what make rs642961 a good candidate for an etiological variant. These findings show that IRF6 and AP-2 alpha are in the same developmental pathway and identify a variant in a regulatory region that contributes substantially to a common complex disorder.

Interactions[edit]

TFAP2A has been shown to interact with:

• APC^[28]
• CITED2^[29][30]
• DEK^[31]
• EP300^[29]
• Myc^[32] and
• P53.^[33]

See also[edit]

• Activating protein 2
• Branchio-oculo-facial syndrome

References[edit]

Further reading[edit]

External links[edit]

• GeneReviews/NCBI/NIH/UW entry on Branchiooculofacial Syndrome
• TFAP2A+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook AP-2alpha
• TFAP2A human gene location in the UCSC Genome Browser.
• TFAP2A human gene details in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.