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| | <StructureSection load='7by1' size='340' side='right'caption='[[7by1]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='7by1' size='340' side='right'caption='[[7by1]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7by1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BY1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7BY1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7by1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BY1 FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kat2a, Gcn5l2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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'>[http://proteopedia.org/fgij/fg.htm?mol=7by1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7by1 OCA], [http://pdbe.org/7by1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7by1 RCSB], [http://www.ebi.ac.uk/pdbsum/7by1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7by1 ProSAT]</span></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=7by1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7by1 OCA], [https://pdbe.org/7by1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7by1 RCSB], [https://www.ebi.ac.uk/pdbsum/7by1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7by1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KAT2A_MOUSE KAT2A_MOUSE]] Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase or succinyltransferase, depending on the context (PubMed:28424240). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (By similarity). Succinylation of histones gives a specific tag for epigenetic transcription activation (By similarity). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (By similarity). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (By similarity). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (By similarity). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:28424240). Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes (By similarity). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (PubMed:25024434). Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression (PubMed:28424240). Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (PubMed:30424580). Regulates embryonic stem cell (ESC) pluripotency and differentiation (PubMed:30270482). Also acetylates non-histone proteins, such as CEBPB, PLK4 and TBX5 (PubMed:17301242). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (By similarity). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (By similarity). Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (By similarity).[UniProtKB:Q92830]<ref>PMID:17301242</ref> <ref>PMID:25024434</ref> <ref>PMID:28424240</ref> <ref>PMID:30270482</ref> <ref>PMID:30424580</ref> | + | [https://www.uniprot.org/uniprot/KAT2A_MOUSE KAT2A_MOUSE] Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase or succinyltransferase, depending on the context (PubMed:28424240). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (By similarity). Succinylation of histones gives a specific tag for epigenetic transcription activation (By similarity). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (By similarity). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (By similarity). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (By similarity). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:28424240). Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes (By similarity). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (PubMed:25024434). Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression (PubMed:28424240). Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (PubMed:30424580). Regulates embryonic stem cell (ESC) pluripotency and differentiation (PubMed:30270482). Also acetylates non-histone proteins, such as CEBPB, PLK4 and TBX5 (PubMed:17301242). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (By similarity). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (By similarity). Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (By similarity).[UniProtKB:Q92830]<ref>PMID:17301242</ref> <ref>PMID:25024434</ref> <ref>PMID:28424240</ref> <ref>PMID:30270482</ref> <ref>PMID:30424580</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | General control non-derepressible 5 (GCN5, also known as Kat2a) and p300/CBP-associated factor (PCAF, also known as Kat2b) are two homologous acetyltransferases. Both proteins share similar domain architecture consisting of a PCAF N-terminal (PCAF_N) domain, acetyltransferase domain and a bromodomain. PCAF also acts as a ubiquitin E3 ligase whose activity is attributable to PCAF_N domain, but its structural aspects are largely unknown. Here, we demonstrated that GCN5 exhibited ubiquitination activity in a similar manner to PCAF and its activity was supported by the ubiquitin-conjugating enzyme UbcH5. Moreover, we determined the crystal structure of PCAF_N domain at 1.8 A resolution and found PCAF_N domain folds into a helical structure with a characteristic binuclear Zn region, which was not predicted from sequence analyses. The Zn region is distinct from that of known E3 ligase structures, suggesting this region may form a new class of E3 ligase. Our biochemical and structural study provides new insight into not only the functional significance of GCN5 but also into ubiquitin biology.
| + | |
| | | | |
| - | Crystal structure of GCN5 PCAF N-terminal domain reveals atypical ubiquitin ligase structure.,Fukai ST, Hibi R, Naganuma T, Sakai M, Saijo S, Shimizu N, Matsumoto M, Shimizu T J Biol Chem. 2020 Aug 19. pii: RA120.013431. doi: 10.1074/jbc.RA120.013431. PMID:32820047<ref>PMID:32820047</ref>
| + | ==See Also== |
| - | | + | *[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 7by1" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 24: |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Hibi, R]] | + | [[Category: Hibi R]] |
| - | [[Category: Shimizu, T]] | + | [[Category: Shimizu T]] |
| - | [[Category: Toma-Fukai, S]] | + | [[Category: Toma-Fukai S]] |
| - | [[Category: Ubiquitin ligase]]
| + | |
| - | [[Category: Unknown function]]
| + | |
| Structural highlights
Function
KAT2A_MOUSE Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase or succinyltransferase, depending on the context (PubMed:28424240). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (By similarity). Succinylation of histones gives a specific tag for epigenetic transcription activation (By similarity). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (By similarity). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (By similarity). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (By similarity). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:28424240). Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes (By similarity). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (PubMed:25024434). Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression (PubMed:28424240). Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (PubMed:30424580). Regulates embryonic stem cell (ESC) pluripotency and differentiation (PubMed:30270482). Also acetylates non-histone proteins, such as CEBPB, PLK4 and TBX5 (PubMed:17301242). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (By similarity). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (By similarity). Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (By similarity).[UniProtKB:Q92830][1] [2] [3] [4] [5]
See Also
References
- ↑ Wiper-Bergeron N, Salem HA, Tomlinson JJ, Wu D, Hache RJ. Glucocorticoid-stimulated preadipocyte differentiation is mediated through acetylation of C/EBPbeta by GCN5. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2703-8. Epub 2007 Feb 14. PMID:17301242 doi:http://dx.doi.org/10.1073/pnas.0607378104
- ↑ Stilling RM, Ronicke R, Benito E, Urbanke H, Capece V, Burkhardt S, Bahari-Javan S, Barth J, Sananbenesi F, Schutz AL, Dyczkowski J, Martinez-Hernandez A, Kerimoglu C, Dent SY, Bonn S, Reymann KG, Fischer A. K-Lysine acetyltransferase 2a regulates a hippocampal gene expression network linked to memory formation. EMBO J. 2014 Sep 1;33(17):1912-27. doi: 10.15252/embj.201487870. Epub 2014 Jul, 14. PMID:25024434 doi:http://dx.doi.org/10.15252/embj.201487870
- ↑ Gao B, Kong Q, Zhang Y, Yun C, Dent SYR, Song J, Zhang DD, Wang Y, Li X, Fang D. The Histone Acetyltransferase Gcn5 Positively Regulates T Cell Activation. J Immunol. 2017 May 15;198(10):3927-3938. doi: 10.4049/jimmunol.1600312. Epub, 2017 Apr 19. PMID:28424240 doi:http://dx.doi.org/10.4049/jimmunol.1600312
- ↑ Moris N, Edri S, Seyres D, Kulkarni R, Domingues AF, Balayo T, Frontini M, Pina C. Histone Acetyltransferase KAT2A Stabilizes Pluripotency with Control of Transcriptional Heterogeneity. Stem Cells. 2018 Dec;36(12):1828-1838. doi: 10.1002/stem.2919. Epub 2018 Oct 17. PMID:30270482 doi:http://dx.doi.org/10.1002/stem.2919
- ↑ Sen R, Pezoa SA, Carpio Shull L, Hernandez-Lagunas L, Niswander LA, Artinger KB. Kat2a and Kat2b Acetyltransferase Activity Regulates Craniofacial Cartilage and Bone Differentiation in Zebrafish and Mice. J Dev Biol. 2018 Nov 12;6(4). pii: jdb6040027. doi: 10.3390/jdb6040027. PMID:30424580 doi:http://dx.doi.org/10.3390/jdb6040027
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