KAT6A

This gene encodes a member of the MOZ, YBFR2, SAS2, TIP60 family of histone acetyltransferases. The protein is composed of a nuclear localization domain, a double C2H2 zinc finger domain that binds to acetylated histone tails, a histone acetyl-transferase domain, a glutamate/aspartate-rich region, and a serine- and methionine-rich transactivation domain. It is part of a complex that acetylates lysine-9 residues in histone 3, and in addition, it acts as a co-activator for several transcription factors. Allelic variants of this gene are associated with an autosomal dominant form of cognitive disability. Chromosomal translocations of this gene are associated with acute myeloid leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

Full Name

Lysine Acetyltransferase 6A

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.

Biological Process

Cellular senescenceManual Assertion Based On ExperimentIMP:UniProtKB
DNA packagingManual Assertion Based On ExperimentTAS:ProtInc
Histone acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H3 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Myeloid cell differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Nucleosome assemblyIEA:InterPro
Positive regulation of gene expressionIEA:Ensembl
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Protein acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of signal transduction by p53 class mediatorTAS:Reactome
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:ComplexPortal

Cellular Location

Nucleus; Nucleus, nucleolus; Nucleus, nucleoplasm; Nucleus, PML body. Recruited into PML body after DNA damage.

Involvement in disease

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).
Arboleda-Tham syndrome (ARTHS):
An autosomal dominant disorder characterized by intellectual disability, dysmorphic facial features, delayed psychomotor development, and lack of speech.

PTM

Autoacetylation at Lys-604 is required for proper function (By similarity).
Autoacetylated.
Phosphorylation at Thr-369 by PKB/AKT1 inhibits its interaction with PML and negatively regulates its acetylation activity towards p53/TP53.