TFAP2A
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| Location (UCSC) | Chr 6: 10.39 – 10.42 Mb | Chr 13: 40.87 – 40.89 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| 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
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
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]
In
Clinical significance
Mutations in the TFAP2A gene cause Branchio-oculo-facial syndrome often with a midline
A disruption of an AP-2 alpha binding site in an
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
TFAP2A has been shown to
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000137203 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021359 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: TFAP2A transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha)".
- S2CID 25657738.
- PMID 3063603.
- PMID 2482225.
- PMID 2010091.
- PMID 1989904.
- PMID 8365563.
- S2CID 581362.
- S2CID 4367622.
- PMID 19376641.
- PMID 21682828.
- S2CID 24698373.
- ^ Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011). "Cleft lip and palate: understanding genetic and environmental influences". Nature Reviews Genetics (12): 167-178.
- ^ Online Mendelian Inheritance in Man (OMIM): 113620
- ^ PMID 18423521.
- ^ PMID 18836445.
- ^ Online Mendelian Inheritance in Man (OMIM): 119300
- PMID 12219090.
- S2CID 3324418.
- PMID 15558496.
- S2CID 25084563.
- PMID 16132054.
- PMID 17438386.
- PMID 15331612.
- ^ PMID 12586840.
- PMID 11744733.
- PMID 12595566.
- PMID 7729426.
- PMID 12226108.
Further reading
- Murphy JE, Keen JH (May 1992). "Recognition sites for clathrin-associated proteins AP-2 and AP-3 on clathrin triskelia". The Journal of Biological Chemistry. 267 (15): 10850–5. PMID 1587861.
- PMID 1916817.
- Williams T, Tjian R (Mar 1991). "Characterization of a dimerization motif in AP-2 and its function in heterologous DNA-binding proteins". Science. 251 (4997): 1067–71. PMID 1998122.
- Williams T, Tjian R (Apr 1991). "Analysis of the DNA-binding and activation properties of the human transcription factor AP-2". Genes & Development. 5 (4): 670–82. PMID 2010091.
- Williams T, Admon A, Lüscher B, Tjian R (Dec 1988). "Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements". Genes & Development. 2 (12A): 1557–69. PMID 3063603.
- Bauer R, Imhof A, Pscherer A, Kopp H, Moser M, Seegers S, Kerscher M, Tainsky MA, Hofstaedter F, Buettner R (Apr 1994). "The genomic structure of the human AP-2 transcription factor". Nucleic Acids Research. 22 (8): 1413–20. PMID 8190633.
- Buettner R, Kannan P, Imhof A, Bauer R, Yim SO, Glockshuber R, Van Dyke MW, Tainsky MA (Jul 1993). "An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2". Molecular and Cellular Biology. 13 (7): 4174–85. PMID 8321221.
- Williamson JA, Bosher JM, Skinner A, Sheer D, Williams T, Hurst HC (Jul 1996). "Chromosomal mapping of the human and mouse homologues of two new members of the AP-2 family of transcription factors". Genomics. 35 (1): 262–4. PMID 8661133.
- Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM (Jun 1997). "Identification of novel human WW domain-containing proteins by cloning of ligand targets". The Journal of Biological Chemistry. 272 (23): 14611–6. PMID 9169421.
- Batsché E, Muchardt C, Behrens J, Hurst HC, Crémisi C (Jul 1998). "RB and c-Myc activate expression of the E-cadherin gene in epithelial cells through interaction with transcription factor AP-2". Molecular and Cellular Biology. 18 (7): 3647–58. PMID 9632747.
- Mertens PR, Alfonso-Jaume MA, Steinmann K, Lovett DH (Dec 1998). "A synergistic interaction of transcription factors AP2 and YB-1 regulates gelatinase A enhancer-dependent transcription". The Journal of Biological Chemistry. 273 (49): 32957–65. PMID 9830047.
- García MA, Campillos M, Marina A, Valdivieso F, Vázquez J (Feb 1999). "Transcription factor AP-2 activity is modulated by protein kinase A-mediated phosphorylation". FEBS Letters. 444 (1): 27–31. S2CID 43874770.
- Rosenthal JA, Chen H, Slepnev VI, Pellegrini L, Salcini AE, Di Fiore PP, De Camilli P (Nov 1999). "The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module". The Journal of Biological Chemistry. 274 (48): 33959–65. PMID 10567358.
- Heicklen-Klein A, Ginzburg I (Oct 2000). "Tau promoter confers neuronal specificity and binds Sp1 and AP-2". Journal of Neurochemistry. 75 (4): 1408–18. S2CID 6558429.
- Nyormoi O, Wang Z, Doan D, Ruiz M, McConkey D, Bar-Eli M (Aug 2001). "Transcription factor AP-2alpha is preferentially cleaved by caspase 6 and degraded by proteasome during tumor necrosis factor alpha-induced apoptosis in breast cancer cells". Molecular and Cellular Biology. 21 (15): 4856–67. PMID 11438643.
- Rao DS, Chang JC, Kumar PD, Mizukami I, Smithson GM, Bradley SV, Parlow AF, Ross TS (Nov 2001). "Huntingtin interacting protein 1 Is a clathrin coat binding protein required for differentiation of late spermatogenic progenitors". Molecular and Cellular Biology. 21 (22): 7796–806. PMID 11604514.
- Bragança J, Swingler T, Marques FI, Jones T, Eloranta JJ, Hurst HC, Shioda T, Bhattacharya S (Mar 2002). "Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2". The Journal of Biological Chemistry. 277 (10): 8559–65. PMID 11744733.
- Mertens PR, Steinmann K, Alfonso-Jaume MA, En-Nia A, Sun Y, Lovett DH (Jul 2002). "Combinatorial interactions of p53, activating protein-2, and YB-1 with a single enhancer element regulate gelatinase A expression in neoplastic cells". The Journal of Biological Chemistry. 277 (28): 24875–82. PMID 11973333.
- Eloranta JJ, Hurst HC (Aug 2002). "Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 and is sumolated in vivo". The Journal of Biological Chemistry. 277 (34): 30798–804. PMID 12072434.
- Ben-Zimra M, Koler M, Orly J (Aug 2002). "Transcription of cholesterol side-chain cleavage cytochrome P450 in the placenta: activating protein-2 assumes the role of steroidogenic factor-1 by binding to an overlapping promoter element". Molecular Endocrinology. 16 (8): 1864–80. PMID 12145340.
External links
- 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.