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Details on Person UniProt:Q9JHD2 Kat2a
| Class:Id | ReferenceGeneProduct:91159 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Sat February 7 2015;chain:2-830 added on Sat February 7 2015;initiator methionine:1 for 91159 removed on Fri Nov 03 2023;initiator methionine: for 91159 added on Fri Nov 03 2023;initiator methionine: for 91159 removed on Fri Aug 15 2025;initiator methionine:1 for 91159 added on Fri Aug 15 2025 |
| _displayName | UniProt:Q9JHD2 Kat2a |
| _timestamp | 2026-02-20 22:00:19 |
| chain | initiator methionine:1 chain:2-830 |
| checksum | 7993CFFEA4734174 |
| comment | FUNCTION Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase, succinyltransferase or malonyltransferase, 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). Has a a strong preference for acetylation of H3 at 'Lys-9' (H3K9ac) (By similarity). Also catalyzes acetylation of histone H1.4 (H1-4) at 'Lys-34' (H1.4K34ac), a modification enriched at promoters of active genes (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, MRE11, PPARGC1A, 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). Acts as a negative regulator of gluconeogenesis by mediating acetylation and subsequent inactivation of PPARGC1A (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).CATALYTIC ACTIVITY L-lysyl-[histone] + acetyl-CoA = N(6)-acetyl-L-lysyl-[histone] + CoA + H(+)CATALYTIC ACTIVITY L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+)CATALYTIC ACTIVITY succinyl-CoA + L-lysyl-[protein] = N(6)-succinyl-L-lysyl-[protein] + CoA + H(+)CATALYTIC ACTIVITY glutaryl-CoA + L-lysyl-[protein] = N(6)-glutaryl-L-lysyl-[protein] + CoA + H(+)SUBUNIT Interacts with EP300, CREBBP and ADA2 (By similarity). 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 (By similarity). Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, KAT2A, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9 (By similarity). The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22 (By similarity). Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (By similarity). In the complex, it probably interacts directly with KAT14, MBIP and WDR5 (By similarity). Interacts with PML (PubMed:22886304). Interacts with CEBPB (PubMed:17301242). Interacts with TACC1, TACC2 and TACC3 (By similarity). Interacts with RELA (PubMed:25024434). Interacts with NFATC2 (PubMed:28424240). Interacts with TBX5 (By similarity). Interacts with PLK4 (By similarity). Associates with the 2-oxoglutarate dehydrogenase complex (By similarity). Interacts with XPC; leading to KAT2A recruitment to promoters and subsequent acetylation of histones (By similarity). Interacts with ERCC3/XPB; leading to KAT2A recruitment to promoters and subsequent acetylation of histones (By similarity). Interacts with ISL1. Interactions of ISL1 with MLIP1 or KAT2A may be mutually exclusive (PubMed:36112854).INTERACTION Mainly localizes to the nucleus. Localizes to sites of DNA damage. Also localizes to centrosomes in late G1 and around the G1/S transition, coinciding with the onset of centriole formation.TISSUE SPECIFICITY In brain, highly expressed in the hippocampal CA1 region (at protein level) (PubMed:25024434). Also expressed in the hippocampal subregions CA3 and the dentate gyrus as well as in the cortex and prefrontal cortex (PubMed:25024434). Expressed at low level in the cerebellum (PubMed:25024434).DEVELOPMENTAL STAGE Expressed uniformly throughout the embryo from 7.5 to 9.0 dpc, except in the distal allantois and developing heart. Gcn5l2 expression is down-regulated after 16.5 dpc, but is later up-regulated in specific adult tissues.DOMAIN Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-638 has an important role in the selective binding of succinyl-CoA over acetyl-CoA.PTM Acetylated at Lys-542, inhibiting the protein acetyltransferase activity (By similarity). Deacetylation at Lys-542 by SIRT6 promotes phosphorylation at Ser-302 and Thr-728 and subsequent activation of the protein acetyltransferase activity, leading to acetylation and inactivation of PPARGC1A (By similarity).DISRUPTION PHENOTYPE Lethality during embryogenesis: embryos develop normally to 7.5 days post coitum (dpc), but growth is severely retarded by 8.5 dpc and embryos fail to form dorsal mesoderm lineages, including chordamesoderm and paraxial mesoderm (PubMed:11017084). Differentiation of extra-embryonic and cardiac mesoderm is not affected (PubMed:11017084). Loss of the dorsal mesoderm lineages is due to an increased apoptosis (PubMed:11017084). Conditional knockout mice lacking Kat2a in the excitatory neurons of the adult forebrain display impaired hippocampus-dependent memory consolidation as well as impaired synaptic and nuclear plasticity (PubMed:25024434). Conditional knockout mice lacking Kat2a in T lymphocytes show defects in T-cell activation, T-cell proliferation, IL2 production and Th1/Th17 regulatory T-cell differentiation (PubMed:28424240). Th2 regulatory T-cell differentiation is not affected (PubMed:28424240).SIMILARITY Belongs to the acetyltransferase family. GCN5 subfamily. |
| description | recommendedName: fullName evidence="15"Histone acetyltransferase KAT2A ecNumber evidence="16"2.3.1.48 alternativeName: fullName evidence="13"General control of amino acid synthesis protein 5-like 2 alternativeName: fullName evidence="14"Histone acetyltransferase GCN5 shortName evidence="14"MmGCN5 alternativeName: fullName evidence="15"Histone glutaryltransferase KAT2A ecNumber evidence="1"2.3.1.- alternativeName: fullName evidence="1"Histone succinyltransferase KAT2A ecNumber evidence="1"2.3.1.- alternativeName: fullName evidence="15"Lysine acetyltransferase 2A |
| geneName | Kat2a Gcn5l2 |
| identifier | Q9JHD2 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Acyltransferase Bromodomain Chromosome Cytoplasm Cytoskeleton Isopeptide bond Nucleus Phosphoprotein Reference proteome Transcription Transcription regulation Transferase Ubl conjugation |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:3445779] Weiser, JD [InstanceEdit:5083144] Weiser, JD [InstanceEdit:5263031] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9015733] Weiser, JD [InstanceEdit:9027688] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9607352] Weiser, JD [InstanceEdit:9616384] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9750299] Weiser, JD [InstanceEdit:9796772] Weiser, Joel [InstanceEdit:9834092] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | Kat2a |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | KAT2A_MOUSE Q3TZ59 |
| sequenceLength | 830 |
| species | [Species:48892] Mus musculus |
| (referenceEntity) | [EntityWithAccessionedSequence:9733789] Kat2a [nucleoplasm] [Mus musculus] |
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No pathways have been reviewed or authored by UniProt:Q9JHD2 Kat2a (91159)
