Q92830 · KAT2A_HUMAN
- ProteinHistone acetyltransferase KAT2A
- GeneKAT2A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids837 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Catalytic activity
- acetyl-CoA + L-lysyl-[histone] = CoA + H+ + N6-acetyl-L-lysyl-[histone]This reaction proceeds in the forward direction.
- acetyl-CoA + L-lysyl-[protein] = CoA + H+ + N6-acetyl-L-lysyl-[protein]
- L-lysyl-[protein] + succinyl-CoA = CoA + H+ + N6-succinyl-L-lysyl-[protein]
- glutaryl-CoA + L-lysyl-[protein] = CoA + H+ + N6-glutaryl-L-lysyl-[protein]This reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.83 μM | acetyl-CoA | |||||
0.91 μM | acetyl-CoA | |||||
0.36 μM | succinyl-CoA | |||||
5.9 μM | acetyl-CoA | in the presence of H3K9 peptide | ||||
45.1 μM | malonyl-CoA | in the presence of H3K9 peptide |
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 575 | Proton donor/acceptor | ||||
Sequence: E | ||||||
Binding site | 579-581 | acetyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: CAV | ||||||
Binding site | 579-581 | succinyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: CAV | ||||||
Binding site | 586-592 | acetyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: QVKGYGT | ||||||
Binding site | 586-592 | succinyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: QVKGYGT | ||||||
Binding site | 617 | acetyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 617 | succinyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: Y |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHistone acetyltransferase KAT2A
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ92830
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 307 | Slightly reduced ability to acetylate and inhibit PPARGC1A. Strongly reduced ability to acetylate and inhibit PPARGC1A; when associated with A-307 and Q-549. | ||||
Sequence: S → A | ||||||
Mutagenesis | 549 | Mimics acetylation; reduced ability to acetylate and inhibit PPARGC1A. Strongly reduced ability to acetylate and inhibit PPARGC1A; when associated with A-307 and A-735. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 567 | Reduced ability to acetylate and inhibit PPARGC1A. | ||||
Sequence: M → A | ||||||
Mutagenesis | 575 | Catalytically dead mutant; abolished acyltransferase activity; when associated with A-615. | ||||
Sequence: E → A | ||||||
Mutagenesis | 601 | Reduced ability to acetylate and inhibit PPARGC1A. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 615 | Catalytically dead mutant; abolished acyltransferase activity; when associated with A-575. | ||||
Sequence: D → A | ||||||
Mutagenesis | 621-622 | Abolised protein acetyltransferase activity. | ||||
Sequence: YF → AA | ||||||
Mutagenesis | 645 | Reduced histone succinylation without affecting histone acetylation. Reduced gene expression. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 735 | Slightly reduced ability to acetylate and inhibit PPARGC1A. Strongly reduced ability to acetylate and inhibit PPARGC1A; when associated with Q-549 and A-735. | ||||
Sequence: T → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 743 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000211202 | 2-837 | UniProt | Histone acetyltransferase KAT2A | |||
Sequence: AEPSQAPTPAPAAQPRPLQSPAPAPTPTPAPSPASAPIPTPTPAPAPAPAAAPAGSTGTGGPGVGSGGAGSGGDPARPGLSQQQRASQRKAQVRGLPRAKKLEKLGVFSACKANETCKCNGWKNPKPPTAPRMDLQQPAANLSELCRSCEHPLADHVSHLENVSEDEINRLLGMVVDVENLFMSVHKEEDTDTKQVYFYLFKLLRKCILQMTRPVVEGSLGSPPFEKPNIEQGVLNFVQYKFSHLAPRERQTMFELSKMFLLCLNYWKLETPAQFRQRSQAEDVATYKVNYTRWLCYCHVPQSCDSLPRYETTHVFGRSLLRSIFTVTRRQLLEKFRVEKDKLVPEKRTLILTHFPKFLSMLEEEIYGANSPIWESGFTMPPSEGTQLVPRPASVSAAVVPSTPIFSPSMGGGSNSSLSLDSAGAEPMPGEKRTLPENLTLEDAKRLRVMGDIPMELVNEVMLTITDPAAMLGPETSLLSANAARDETARLEERRGIIEFHVIGNSLTPKANRRVLLWLVGLQNVFSHQLPRMPKEYIARLVFDPKHKTLALIKDGRVIGGICFRMFPTQGFTEIVFCAVTSNEQVKGYGTHLMNHLKEYHIKHNILYFLTYADEYAIGYFKKQGFSKDIKVPKSRYLGYIKDYEGATLMECELNPRIPYTELSHIIKKQKEIIKKLIERKQAQIRKVYPGLSCFKEGVRQIPVESVPGIRETGWKPLGKEKGKELKDPDQLYTTLKNLLAQIKSHPSAWPFMEPVKKSEAPDYYEVIRFPIDLKTMTERLRSRYYVTRKLFVADLQRVIANCREYNPPDSEYCRCASALEKFFYFKLKEGGLIDK | |||||||
Modified residue | 307 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 549 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Cross-link | 728 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 734 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 735 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Cross-link | 759 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Cross-link | 791 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K |
Post-translational modification
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).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with EP300, CREBBP and ADA2. Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TAF3, TADA3L, SUPT3H/SPT3, TAF2/TAFII150, TAF4/TAFII135, TAF5/TAFII100, KAT2A/GCN5L2, TAF10 and TRRAP (PubMed:10373431, PubMed:10611234, PubMed:11438666).
Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, KAT2A, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9 (PubMed:18206972).
The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22 (PubMed:18206972).
Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (PubMed:19103755).
In the complex, it probably interacts directly with KAT14, MBIP and WDR5 (PubMed:19103755).
Interacts with PML (By similarity).
Interacts with CEBPB (PubMed:17301242).
Interacts with TACC1, TACC2 and TACC3 (PubMed:14767476).
Interacts with RELA (By similarity).
Interacts with NFATC2 (By similarity).
Interacts with TBX5 (PubMed:29174768).
Interacts with PLK4 (PubMed:27796307).
Associates with the 2-oxoglutarate dehydrogenase complex (PubMed:29211711).
Interacts with XPC; leading to KAT2A recruitment to promoters and subsequent acetylation of histones (PubMed:29973595, PubMed:31527837).
Interacts with ERCC3/XPB; leading to KAT2A recruitment to promoters and subsequent acetylation of histones (PubMed:30894545).
Interacts with ISL1. Interactions of ISL1 with MLIP1 or KAT2A may be mutually exclusive (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q92830 | AATF Q9NY61 | 4 | EBI-477622, EBI-372428 | |
BINARY | Q92830 | E2F1 Q01094 | 3 | EBI-477622, EBI-448924 | |
XENO | Q92830 | N P0DTC9 | 2 | EBI-477622, EBI-25475856 | |
XENO | Q92830 | N P59595 | 2 | EBI-477622, EBI-7602718 | |
BINARY | Q92830 | TADA2A O75478 | 5 | EBI-477622, EBI-742268 | |
BINARY | Q92830 | WDHD1 O75717 | 5 | EBI-477622, EBI-3951691 | |
BINARY | Q92830 | ZZZ3 Q8IYH5 | 2 | EBI-477622, EBI-2795524 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-99 | Disordered | ||||
Sequence: MAEPSQAPTPAPAAQPRPLQSPAPAPTPTPAPSPASAPIPTPTPAPAPAPAAAPAGSTGTGGPGVGSGGAGSGGDPARPGLSQQQRASQRKAQVRGLPR | ||||||
Compositional bias | 9-51 | Pro residues | ||||
Sequence: TPAPAAQPRPLQSPAPAPTPTPAPSPASAPIPTPTPAPAPAPA | ||||||
Compositional bias | 407-423 | Polar residues | ||||
Sequence: FSPSMGGGSNSSLSLDS | ||||||
Region | 407-434 | Disordered | ||||
Sequence: FSPSMGGGSNSSLSLDSAGAEPMPGEKR | ||||||
Domain | 503-656 | N-acetyltransferase | ||||
Sequence: VIGNSLTPKANRRVLLWLVGLQNVFSHQLPRMPKEYIARLVFDPKHKTLALIKDGRVIGGICFRMFPTQGFTEIVFCAVTSNEQVKGYGTHLMNHLKEYHIKHNILYFLTYADEYAIGYFKKQGFSKDIKVPKSRYLGYIKDYEGATLMECELN | ||||||
Region | 639-648 | Loop 3 | ||||
Sequence: LGYIKDYEGA | ||||||
Domain | 745-815 | Bromo | ||||
Sequence: KSHPSAWPFMEPVKKSEAPDYYEVIRFPIDLKTMTERLRSRYYVTRKLFVADLQRVIANCREYNPPDSEYC |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q92830-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsGCN5-L
- Length837
- Mass (Da)93,926
- Last updated2008-10-14 v3
- Checksum728CC8ACF08600EA
Q92830-2
- Name2
- SynonymsGCN5-S
- Differences from canonical
- 1-410: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_000556 | 1-410 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 9-51 | Pro residues | ||||
Sequence: TPAPAAQPRPLQSPAPAPTPTPAPSPASAPIPTPTPAPAPAPA | ||||||
Sequence conflict | 116 | in Ref. 1; AAC39769 | ||||
Sequence: E → G | ||||||
Sequence conflict | 134 | in Ref. 1; AAC39769 | ||||
Sequence: M → I | ||||||
Sequence conflict | 269 | in Ref. 1; AAC39769 | ||||
Sequence: K → E | ||||||
Compositional bias | 407-423 | Polar residues | ||||
Sequence: FSPSMGGGSNSSLSLDS |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF029777 EMBL· GenBank· DDBJ | AAC39769.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471152 EMBL· GenBank· DDBJ | EAW60803.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC032743 EMBL· GenBank· DDBJ | AAH32743.1 EMBL· GenBank· DDBJ | mRNA | ||
BC039907 EMBL· GenBank· DDBJ | AAH39907.1 EMBL· GenBank· DDBJ | mRNA | ||
BC105977 EMBL· GenBank· DDBJ | AAI05978.1 EMBL· GenBank· DDBJ | mRNA | ||
U57316 EMBL· GenBank· DDBJ | AAC50641.1 EMBL· GenBank· DDBJ | Genomic DNA |