UniProt functional annotation for Q92830



	UniProt functional annotation for Q92830

UniProt code: Q92830.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase or succinyltransferase, depending on the context (PubMed:29211711). 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). 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, PLK4 and TBX5 (PubMed:17301242, PubMed:27796307, PubMed:29174768). 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). 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). {ECO:0000250|UniProtKB:Q9JHD2, ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:31527837, ECO:0000269|PubMed:31542297}.

Function: (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. {ECO:0000269|PubMed:11384967}.

Catalytic activity: Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L- lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; Evidence={ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768};

Catalytic activity: Reaction=acetyl-CoA + L-lysyl-[histone] = CoA + H(+) + N(6)-acetyl-L- lysyl-[histone]; Xref=Rhea:RHEA:21992, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:11338, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48; Evidence={ECO:0000269|PubMed:27377381, ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:31527837}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21993; Evidence={ECO:0000269|PubMed:27377381, ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:31527837};

Catalytic activity: Reaction=L-lysyl-[protein] + succinyl-CoA = CoA + H(+) + N(6)-succinyl- L-lysyl-[protein]; Xref=Rhea:RHEA:16261, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11877, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57292, ChEBI:CHEBI:87830; Evidence={ECO:0000269|PubMed:29211711};

Catalytic activity: Reaction=glutaryl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-glutaryl- L-lysyl-[protein]; Xref=Rhea:RHEA:18009, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11875, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57378, ChEBI:CHEBI:87828; Evidence={ECO:0000269|PubMed:31542297}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18010; Evidence={ECO:0000269|PubMed:31542297};

Biophysicochemical properties: Kinetic parameters: KM=0.83 uM for acetyl-CoA {ECO:0000269|PubMed:29211711}; KM=0.91 uM for acetyl-CoA {ECO:0000269|PubMed:27377381}; KM=0.36 uM for succinyl-CoA {ECO:0000269|PubMed:29211711};

Subunit: Homooligomer; may form a tetramer of homodimers (PubMed:30109122). 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). {ECO:0000250|UniProtKB:Q9JHD2, ECO:0000269|PubMed:10373431, ECO:0000269|PubMed:10611234, ECO:0000269|PubMed:11438666, ECO:0000269|PubMed:14767476, ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:18206972, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:30109122, ECO:0000269|PubMed:30894545, ECO:0000269|PubMed:31527837}.

Subunit: (Microbial infection) Interacts with and acetylates HIV-1 Tat. {ECO:0000269|PubMed:11384967}.

Subcellular location: Nucleus {ECO:0000269|PubMed:11564863, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29211711}. Chromosome {ECO:0000269|PubMed:29211711}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:27796307}. Note=Mainly localizes to the nucleus (PubMed:27796307). Also localizes to centrosomes in late G1 and around the G1/S transition, coinciding with the onset of centriole formation (PubMed:27796307). {ECO:0000269|PubMed:27796307}.

Tissue specificity: Expressed in all tissues tested, with most abundant expression in ovary.

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. {ECO:0000269|PubMed:29211711}.

Similarity: Belongs to the acetyltransferase family. GCN5 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase or succinyltransferase, depending on the context (PubMed:29211711). 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). 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, PLK4 and TBX5 (PubMed:17301242, PubMed:27796307, PubMed:29174768). 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). 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). {ECO:0000250\|UniProtKB:Q9JHD2, ECO:0000269\|PubMed:17301242, ECO:0000269\|PubMed:19103755, ECO:0000269\|PubMed:27796307, ECO:0000269\|PubMed:29174768, ECO:0000269\|PubMed:29211711, ECO:0000269\|PubMed:29973595, ECO:0000269\|PubMed:31527837, ECO:0000269\|PubMed:31542297}.



Function:		(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. {ECO:0000269\|PubMed:11384967}.


Catalytic activity:		Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L- lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; Evidence={ECO:0000269\|PubMed:17301242, ECO:0000269\|PubMed:27796307, ECO:0000269\|PubMed:29174768};
Catalytic activity:		Reaction=acetyl-CoA + L-lysyl-[histone] = CoA + H(+) + N(6)-acetyl-L- lysyl-[histone]; Xref=Rhea:RHEA:21992, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:11338, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48; Evidence={ECO:0000269\|PubMed:27377381, ECO:0000269\|PubMed:29211711, ECO:0000269\|PubMed:31527837}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21993; Evidence={ECO:0000269\|PubMed:27377381, ECO:0000269\|PubMed:29211711, ECO:0000269\|PubMed:31527837};
Catalytic activity:		Reaction=L-lysyl-[protein] + succinyl-CoA = CoA + H(+) + N(6)-succinyl- L-lysyl-[protein]; Xref=Rhea:RHEA:16261, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11877, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57292, ChEBI:CHEBI:87830; Evidence={ECO:0000269\|PubMed:29211711};
Catalytic activity:		Reaction=glutaryl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-glutaryl- L-lysyl-[protein]; Xref=Rhea:RHEA:18009, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11875, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57378, ChEBI:CHEBI:87828; Evidence={ECO:0000269\|PubMed:31542297}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18010; Evidence={ECO:0000269\|PubMed:31542297};
Biophysicochemical properties:		Kinetic parameters: KM=0.83 uM for acetyl-CoA {ECO:0000269\|PubMed:29211711}; KM=0.91 uM for acetyl-CoA {ECO:0000269\|PubMed:27377381}; KM=0.36 uM for succinyl-CoA {ECO:0000269\|PubMed:29211711};
Subunit:		Homooligomer; may form a tetramer of homodimers (PubMed:30109122). 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). {ECO:0000250\|UniProtKB:Q9JHD2, ECO:0000269\|PubMed:10373431, ECO:0000269\|PubMed:10611234, ECO:0000269\|PubMed:11438666, ECO:0000269\|PubMed:14767476, ECO:0000269\|PubMed:17301242, ECO:0000269\|PubMed:18206972, ECO:0000269\|PubMed:19103755, ECO:0000269\|PubMed:27796307, ECO:0000269\|PubMed:29174768, ECO:0000269\|PubMed:29211711, ECO:0000269\|PubMed:29973595, ECO:0000269\|PubMed:30109122, ECO:0000269\|PubMed:30894545, ECO:0000269\|PubMed:31527837}.
Subunit:		(Microbial infection) Interacts with and acetylates HIV-1 Tat. {ECO:0000269\|PubMed:11384967}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:11564863, ECO:0000269\|PubMed:27796307, ECO:0000269\|PubMed:29211711}. Chromosome {ECO:0000269\|PubMed:29211711}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:27796307}. Note=Mainly localizes to the nucleus (PubMed:27796307). Also localizes to centrosomes in late G1 and around the G1/S transition, coinciding with the onset of centriole formation (PubMed:27796307). {ECO:0000269\|PubMed:27796307}.
Tissue specificity:		Expressed in all tissues tested, with most abundant expression in ovary.
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. {ECO:0000269\|PubMed:29211711}.
Similarity:		Belongs to the acetyltransferase family. GCN5 subfamily. {ECO:0000305}.