KAT2A
Domain
Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-645 has an important role in the selective binding of succinyl-CoA over acetyl-CoA.
Function
Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase, succinyltransferase or malonyltransferase, depending on the context (PubMed:29211711, PubMed:35995428). 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 (PubMed:29211711). Succinylation of histones gives a specific tag for epigenetic transcription activation (PubMed:29211711). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (PubMed:29211711). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (PubMed:17301242, PubMed:19103755, PubMed:29211711). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (PubMed:17301242, PubMed:19103755, PubMed:21131905). Has a a strong preference for acetylation of H3 at 'Lys-9' (H3K9ac) (PubMed:21131905). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:17301242, PubMed:19103755, PubMed:29211711). 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 (PubMed:29973595, PubMed:31527837). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (By similarity). 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 (By similarity). Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (By similarity). Regulates embryonic stem cell (ESC) pluripotency and differentiation (By similarity). Also acetylates non-histone proteins, such as CEBPB, MRE11, PPARGC1A, PLK4 and TBX5 (PubMed:16753578, PubMed:17301242, PubMed:27796307, PubMed:29174768, PubMed:38128537). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Acts as a negative regulator of gluconeogenesis by mediating acetylation and subsequent inactivation of PPARGC1A (PubMed:16753578, PubMed:23142079). 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 (PubMed:31542297).
(Microbial infection) 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.
Post-translational modifications
Acetylated at Lys-549, inhibiting the protein acetyltransferase activity (PubMed:23142079). Deacetylation at Lys-549 by SIRT6 promotes phosphorylation at Ser-307 and Thr-735 and subsequent activation of the protein acetyltransferase activity, leading to acetylation and inactivation of PPARGC1A (PubMed:23142079).
Sequence Similarities
Belongs to the acetyltransferase family. GCN5 subfamily.
Tissue Specificity
Expressed in all tissues tested.
Cellular localization
- Nucleus
- Chromosome
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Mainly localizes to the nucleus (PubMed:27796307). Localizes to sites of DNA damage (PubMed:25593309). Also localizes to centrosomes in late G1 and around the G1/S transition, coinciding with the onset of centriole formation (PubMed:27796307).
Alternative names
GCN5, GCN5L2, KAT2A, Histone acetyltransferase KAT2A, General control of amino acid synthesis protein 5-like 2, Histone acetyltransferase GCN5, Histone glutaryltransferase KAT2A, Histone succinyltransferase KAT2A, Lysine acetyltransferase 2A, STAF97, hGCN5