View source for 6fgn


==Solution Structure of p300Taz2-p63TA==
<StructureSection load='6fgn' size='340' side='right'caption='[[6fgn]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fgn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FGN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6fgn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fgn OCA], [https://pdbe.org/6fgn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fgn RCSB], [https://www.ebi.ac.uk/pdbsum/6fgn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fgn ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/EP300_HUMAN EP300_HUMAN] Note=Defects in EP300 may play a role in epithelial cancer.  Note=Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with KAT6A.  Defects in EP300 are the cause of Rubinstein-Taybi syndrome type 2 (RSTS2) [MIM:[https://omim.org/entry/613684 613684]. A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies. Some individuals with RSTS2 have less severe mental impairment, more severe microcephaly, and a greater degree of changes in facial bone structure than RSTS1 patients.<ref>PMID:15706485</ref> [https://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN] Defects in TP63 are the cause of acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:[https://omim.org/entry/103285 103285]; a form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and loss of permanent teeth. ADULT differs significantly from EEC3 syndrome by the absence of facial clefting.  Defects in TP63 are the cause of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:[https://omim.org/entry/106260 106260]. AEC is an autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate.<ref>PMID:11159940</ref>   Defects in TP63 are the cause of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome type 3 (EEC3) [MIM:[https://omim.org/entry/604292 604292]. EEC3 is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting.<ref>PMID:10535733</ref> <ref>PMID:10839977</ref> <ref>PMID:11462173</ref> <ref>PMID:12838557</ref>   Defects in TP63 are the cause of split-hand/foot malformation type 4 (SHFM4) [MIM:[https://omim.org/entry/605289 605289]. Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. There is restricted overlap between the mutational spectra of EEC3 and SHFM4.<ref>PMID:10839977</ref> <ref>PMID:11462173</ref>   Defects in TP63 are the cause of limb-mammary syndrome (LMS) [MIM:[https://omim.org/entry/603543 603543]. LMS is characterized by ectrodactyly, cleft palate and mammary-gland abnormalities.<ref>PMID:11462173</ref>   Note=Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers.  Defects in TP63 are a cause of ectodermal dysplasia Rapp-Hodgkin type (EDRH) [MIM:[https://omim.org/entry/129400 129400]; also called Rapp-Hodgkin syndrome or anhidrotic ectodermal dysplasia with cleft lip/palate. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDRH is characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate.<ref>PMID:12939657</ref> <ref>PMID:12766194</ref> <ref>PMID:15200513</ref> <ref>PMID:16740912</ref>   Defects in TP63 are the cause of non-syndromic orofacial cleft type 8 (OFC8) [MIM:[https://omim.org/entry/129400 129400]. Non-syndromic orofacial cleft is a common birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.
== Function ==
[https://www.uniprot.org/uniprot/EP300_HUMAN EP300_HUMAN] Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Also functions as acetyltransferase for nonhistone targets. Acetylates 'Lys-131' of ALX1 and acts as its coactivator in the presence of CREBBP. Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function. Acetylates HDAC1 leading to its inactivation and modulation of transcription. Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2. Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement. Can also mediate transcriptional repression. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Acetylates FOXO1 and enhances its transcriptional activity.<ref>PMID:11701890</ref> <ref>PMID:10733570</ref> <ref>PMID:11430825</ref> <ref>PMID:12586840</ref> <ref>PMID:12929931</ref> <ref>PMID:15186775</ref> <ref>PMID:15890677</ref> <ref>PMID:16762839</ref> <ref>PMID:18722353</ref> [https://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Despite high sequence homology among the p53 family members, the regulation of their transactivation potential is based on strikingly different mechanisms. Previous studies revealed that the activity of TAp63alpha is regulated via an autoinhibitory mechanism that keeps inactive TAp63alpha in a dimeric conformation. While all p73 isoforms are constitutive tetramers, their basal activity is much lower compared with tetrameric TAp63. We show that the dimeric state of TAp63alpha not only reduces DNA binding affinity, but also suppresses interaction with the acetyltransferase p300. Exchange of the transactivation domains is sufficient to transfer the regulatory characteristics between p63 and p73. Structure determination of the transactivation domains of p63 and p73 in complex with the p300 Taz2 domain further revealed that, in contrast to p53 and p73, p63 has a single transactivation domain. Sequences essential for stabilizing the closed dimer of TAp63alpha have evolved into a second transactivation domain in p73 and p53.

Regulation of the Activity in the p53 Family Depends on the Organization of the Transactivation Domain.,Krauskopf K, Gebel J, Kazemi S, Tuppi M, Lohr F, Schafer B, Koch J, Guntert P, Dotsch V, Kehrloesser S Structure. 2018 Aug 7;26(8):1091-1100.e4. doi: 10.1016/j.str.2018.05.013. Epub, 2018 Jun 28. PMID:30099987<ref>PMID:30099987</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fgn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dotsch V]]
[[Category: Gebel J]]
[[Category: Guntert P]]
[[Category: Kazemi S]]
[[Category: Lohr F]]