UniProt functional annotation for Q92794



	UniProt functional annotation for Q92794

UniProt code: Q92794.

Organism: Homo sapiens (Human).

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

Function: Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2. Acetylates p53/TP53 at 'Lys-120' and 'Lys-382' and controls its transcriptional activity via association with PML. {ECO:0000269|PubMed:11742995, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:12771199, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:17925393, ECO:0000269|PubMed:23431171}.

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; EC=2.3.1.48; Evidence={ECO:0000269|PubMed:11313971, ECO:0000269|PubMed:11742995, ECO:0000269|PubMed:17925393};

Subunit: Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts with RUNX1; phosphorylation of RUNX1 enhances the interaction. Interacts with RUNX2. Interacts with p53/TP53. Interacts with PML (isoform PML-4) and this interaction positively regulates its acetylation activity towards p53/TP53. {ECO:0000269|PubMed:11742995, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:18794358, ECO:0000269|PubMed:23431171, ECO:0000269|Ref.27}.

Subcellular location: Nucleus. Nucleus, nucleolus. Nucleus, nucleoplasm. Nucleus, PML body. Note=Recruited into PML body after DNA damage.

Domain: The N-terminus is involved in transcriptional activation while the C-terminus is involved in transcriptional repression. {ECO:0000269|PubMed:11313971}.

Ptm: Autoacetylation at Lys-604 is required for proper function (By similarity). Autoacetylated. {ECO:0000250|UniProtKB:Q9H7Z6, ECO:0000269|Ref.27}.

Ptm: Phosphorylation at Thr-369 by PKB/AKT1 inhibits its interaction with PML and negatively regulates its acetylation activity towards p53/TP53. {ECO:0000269|PubMed:11742995, ECO:0000269|PubMed:23431171}.

Disease: Note=Chromosomal aberrations involving KAT6A may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with CREBBP (PubMed:8782817). Translocation t(8;22)(p11;q13) with EP300 (PubMed:10824998). KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription (PubMed:11742995). Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation (PubMed:12676584). {ECO:0000269|PubMed:10824998, ECO:0000269|PubMed:11742995, ECO:0000269|PubMed:12676584, ECO:0000269|PubMed:8782817}.

Disease: Note=A chromosomal aberration involving KAT6A is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with ASXL2 generates a KAT6A-ASXL2 fusion protein. {ECO:0000269|Ref.3}.

Disease: Arboleda-Tham syndrome (ARTHS) [MIM:616268]: An autosomal dominant disorder characterized by intellectual disability, dysmorphic facial features, delayed psychomotor development, and lack of speech. {ECO:0000269|PubMed:25728775, ECO:0000269|PubMed:25728777}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the MYST (SAS/MOZ) family. {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:		Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2. Acetylates p53/TP53 at 'Lys-120' and 'Lys-382' and controls its transcriptional activity via association with PML. {ECO:0000269\|PubMed:11742995, ECO:0000269\|PubMed:11965546, ECO:0000269\|PubMed:12771199, ECO:0000269\|PubMed:16387653, ECO:0000269\|PubMed:17925393, ECO:0000269\|PubMed:23431171}.


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; EC=2.3.1.48; Evidence={ECO:0000269\|PubMed:11313971, ECO:0000269\|PubMed:11742995, ECO:0000269\|PubMed:17925393};
Subunit:		Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts with RUNX1; phosphorylation of RUNX1 enhances the interaction. Interacts with RUNX2. Interacts with p53/TP53. Interacts with PML (isoform PML-4) and this interaction positively regulates its acetylation activity towards p53/TP53. {ECO:0000269\|PubMed:11742995, ECO:0000269\|PubMed:11965546, ECO:0000269\|PubMed:16387653, ECO:0000269\|PubMed:18794358, ECO:0000269\|PubMed:23431171, ECO:0000269\|Ref.27}.
Subcellular location:		Nucleus. Nucleus, nucleolus. Nucleus, nucleoplasm. Nucleus, PML body. Note=Recruited into PML body after DNA damage.
Domain:		The N-terminus is involved in transcriptional activation while the C-terminus is involved in transcriptional repression. {ECO:0000269\|PubMed:11313971}.
Ptm:		Autoacetylation at Lys-604 is required for proper function (By similarity). Autoacetylated. {ECO:0000250\|UniProtKB:Q9H7Z6, ECO:0000269\|Ref.27}.
Ptm:		Phosphorylation at Thr-369 by PKB/AKT1 inhibits its interaction with PML and negatively regulates its acetylation activity towards p53/TP53. {ECO:0000269\|PubMed:11742995, ECO:0000269\|PubMed:23431171}.
Disease:		Note=Chromosomal aberrations involving KAT6A may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with CREBBP (PubMed:8782817). Translocation t(8;22)(p11;q13) with EP300 (PubMed:10824998). KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription (PubMed:11742995). Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation (PubMed:12676584). {ECO:0000269\|PubMed:10824998, ECO:0000269\|PubMed:11742995, ECO:0000269\|PubMed:12676584, ECO:0000269\|PubMed:8782817}.
Disease:		Note=A chromosomal aberration involving KAT6A is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with ASXL2 generates a KAT6A-ASXL2 fusion protein. {ECO:0000269\|Ref.3}.
Disease:		Arboleda-Tham syndrome (ARTHS) [MIM:616268]: An autosomal dominant disorder characterized by intellectual disability, dysmorphic facial features, delayed psychomotor development, and lack of speech. {ECO:0000269\|PubMed:25728775, ECO:0000269\|PubMed:25728777}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the MYST (SAS/MOZ) family. {ECO:0000305}.