| 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]
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[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Fukai ST, Hibi R, Naganuma T, Sakai M, Saijo S, Shimizu N, Matsumoto M, Shimizu T. Crystal structure of GCN5 PCAF N-terminal domain reveals atypical ubiquitin ligase structure. J Biol Chem. 2020 Aug 19. pii: RA120.013431. doi: 10.1074/jbc.RA120.013431. PMID:32820047 doi:http://dx.doi.org/10.1074/jbc.RA120.013431
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