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FLASH GENE
Symbol KAT6A contributors: mct/npt/pgu - updated : 25-03-2015
HGNC name K(lysine) acetyltransferase 6A
HGNC id 13013
Corresponding disease
AMLT3 acute myeloid leukemia M4/M5 displaying monocytic differentiation erythrophagocytosis by the leukemic cells,poor response to chemotherapy,with translocation t(8;16)(p11;p13) and inversion inv(8) (p11;q13) and acute monocytic leukemia with t(8;22) (p11;q13)
MRD32 mental retardation, autosomal dominant 32
Location 8p11.21      Physical location : -
Synonym name
  • histone acetyltransferase
  • runt-related transcription factor binding protein 2
  • monocytic leukemia zinc finger protein
  • MOZ, YBF2/SAS3, SAS2 and TIP60 protein 3
  • MYST histone acetyltransferase (monocytic leukemia) 3
  • Synonym symbol(s) MOZ, HAT, ZNF220, RUNXBP2, MYST3, MGC167033
    EC.number 2.3.1.48
    DNA
    TYPE functioning gene
    STRUCTURE 122.51 kb     17 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map pter - D8S505 - D8S1722 - D8S536 - D8S1817 - D8S532 - MYST3 - D8S519 - qter
    Authors Gene Map (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 9241 - 2004 - 2001 11313971
    18 - 9285 - 2004 - 2001 11313971
    17 - 9153 - 2004 - 2001 11313971
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately Homo sapiens
    Digestivepharynx   highly
    Lymphoid/Immunethymus    
    Nervousbrain   highly Homo sapiens
    Reproductivemale systemprostate   
    Respiratorylung    
     respiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two C4HC3 zinc finger protein motifs
  • two nuclear bipartite localization signals (NLS1,NLS2)
  • a putative histone acetyltransferase, (MYST domain)
  • an acidic proline-glutamine and a methionine-rich domain (SM domain)
  • a HAT domain containing a central region that is structurally and functionally conserved with the yeast, and harboring a DNA-binding activity
  • a nuclear localization domain (including H15),
  • a double-plant homeodomain finger that binds to acetylated histone H3 tails (PHD 1 and 2)
  • an acidic glutamate/aspartate-rich region, and a serine and methionine-rich region that comprises a transactivation domain
  • large multidomain protein that contains, besides others, a histone acetyl transferase catalytic domain
  • HOMOLOGY
    interspecies homolog to yeast silencing SAS2
    homolog to murine Myst3
    intraspecies homolog to MORF
    Homologene
    FAMILY
  • MYST [MOZ, Ybf2/Sas3, Sas2 and TIP60 (Tat-interacting protein, 60 kDa)] acetyltransferase family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,nucleosome
    text
  • localizes to the MEIS1 locus in pre-B-cells and maintains MEIS1 expression
  • basic FUNCTION
  • involved in chromatin remodeling and general gene expression
  • involved in regulating transcriptional activation mediated by RUNX2
  • essential transcriptional coactivator and histone acetyltransferase (HAT) that plays a primary role in the differentiation of erythroid and myeloid cells and is required to maintain hematopoietic stem cells
  • DNA-binding activity of MYST3 may be at the heart of the oncogenic effect in AML-associated chromosomal translocations
  • acting as a transcriptional coactivator for AML1, which is essential for establishment of definitive hematopoiesis
  • involved in regulating cell-cycle arrest in the G1 phase
  • essential for the generation and maintenance of hematopoietic stem cells (HSC) and for the appropriate development of myeloid, erythroid and B-lineage cell progenitors
  • regulates H3K9 acetylation at Hox gene loci and retinoic acid can act independently of MYST3 to establish specific Hox gene expression boundaries
  • critical requirement in hematopoietic stem cell development and maintenance
  • specifically required for the H3K9 acetylation of transcriptionally active Hox gene loci
  • KAT6A/KAT6B are histone acetyltransferase (HATs) important for different developmental programs and have been implicated in leukemogenic and other tumorigenic processess
  • tandem PHD fingers of KAT6A/KAT6B acetyltransferases display selectivity for acetylated histone H3 and are required for the association with chromatin
  • has important roles in gene-specific histone acetylation, regulating developmental gene expression and in TP53 acetylation and signaling
  • critical function in haematopoiesis
  • induces alpha-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification
  • role of wild-type KAT6A in regulating B-cell progenitor proliferation and hematopoietic malignancy.
  • required to maintain the proliferative capacity of B-cell progenitors, even in the presence of MYC overexpression, by directly maintaining the transcriptional activity of genes required for normal B-cell development
  • through histone and non-histone acetylation, KAT6A affects multiple cellular processes and illustrates the complex role of acetylation in regulating development and disease
  • is a potent inhibitor of senescence via the CDKN2A pathway
  • KAT6A and BMI1, respectively, promoted and repressed HOX genes during the shift from the transcriptionally repressed to the active state
  • CELLULAR PROCESS nucleotide, chromatin organization, remodeling
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text chromatin structure
    PATHWAY
    metabolism
    signaling
    a component
  • forms a complex with TP53 to induce CDKN1A expression and cell-cycle arrest
  • KAT6A and the related factor KAT6B form tetrameric complexes with ING5 (inhibitor of growth 5), MEAF6 (Esa1-associated factor 6 ortholog), and the bromodomain-PHD finger protein BRPF1, BRD1, or BRPF3
  • INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • RUNX1 (inhibition by the fusion gene RUNXBP2-CREBBP)
  • RUNX2 (throught the SM domain)
  • able to interact with SPI1 and activate SPI1-dependent transcription, thus suggesting a physical and functional link between SPI1 and MYST3
  • role of the interaction between KAT6A and KMT2A in CD34+ cells in which both proteins have a critical role in hematopoietic cell-fate decision, suggesting a new molecular mechanism by which KAT6A or KMT2A deregulation leads to leukemogenesis
  • regulates the TBX1 locus, and MYST3 mutation partially phenocopies DiGeorge syndrome in mouse
  • directly interacts with TP53 and is essential for TP53-dependent selective regulation of CDKN1A expression
  • is recruited into promyelocytic leukemia nuclear bodies after DNA damage
  • AKT1-mediated phosphorylation of KAT6A suppresses the interaction between PML and KAT6A
  • is crucial for TP53-mediated CDKN1A expression induced by PML expression and the ensuing PML-induced senescence
  • is an acetylation regulator of TP53
  • SYMPK interacts and co-localizes with both KAT6A and KMT2A in immature hematopoietic cells
  • is an upstream inhibitor of the CDKN2A pathway
  • BRPF1 activating 3 lysine acetyltransferases (KAT6A, KAT6B, and KAT7), suggesting that this protein has the potential to stimulate crosstalk between different chromatin modifications
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AMLT3 , MRD32
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with NCOA2 in acute myelomonocytic leukemia
    tumoral fusion      
    with NCOA3, fusion partner for MYST3 in M5 acute myeloid leukemia
    tumoral fusion      
    fusion genes, such as MYST3-NCOA2, MYST3-CREBBP and MYST3-EP300, in acute myeloid leukemia (AML) by chromosomal translocation
    Susceptibility
    Variant & Polymorphism
    Candidate gene may contribute to the wide variability in severity of velocardio-facial(VCF)/DiGeorge syndrome
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    inhibiting KAT6A may be one way to induce senescence in proliferative tumour cells
    ANIMAL & CELL MODELS
  • during early hepatocarcinogenesis, aberrantly expressed MOZ may induce Gstp1 expression through the Nrf2-mediated pathway in rat
  • DiGeorge syndrome-like anomalies are present in mice with homozygous mutation of Moz and in heterozygous Moz mutants when combined with Tbx1 haploinsufficiency or oversupply of retinoic acid