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FLASH GENE
Symbol KAT2A contributors: shn/npt/pgu - updated : 06-03-2019
HGNC name K(lysine) acetyltransferase 2A
HGNC id 4201
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an acetyltransferase domain
  • a bromadomain
  • HOMOLOGY
    interspecies homolog to yeast GCN5 general control of amino-acid synthesis 2
    ortholog to Kat2b, Danio rerio
    ortholog to Kat2b, Mus musculus
    Homologene
    FAMILY
  • GNAT family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • transcriptional activator, having a mechanistic role in the repression of transcription following DNA damage
  • a significant histone acetyltransferase activity with core histones, but not with nucleosome core particles
  • enhancing the initial rate of RNA polymerase II mediated transcription
  • required with TRRAP for c-Myc to promote cell growth and transformation
  • may be required for cell survival and mesoderm formation during mammalian development
  • may implicated in P53 transactivation
  • participates in the ubiquitination process as an accessory factor for a ubiquitin ligase
  • modulates chromatin structure not only through the acetylation of histones, but also by directly acetylating SMARCA4
  • regulates the activation of PI3K/Akt survival pathway in B cells exposed to oxidative stress (exogenous H2O2) via controlling gene expressions of SYK and BTk
  • first identified transcription-related histone acetyltransferases that has been implicated in the regulation of diverse cellular functions
  • PTGES3 and KAT2A were required to maintain open chromatin regions along the genome indicating that dynamic protein behavior is a critical feature of various DNA-associated events
  • PTGES3 molecular chaperone works in conjunction with the KAT2A acetyltransferase to mediate the dynamics of heterologous protein-DNA complexes, which impact both RNA transcription and open chromatin processes
  • PTGES3 molecular chaperone and KAT2A acetyltransferase cooperate to modulate the stabilities of a wide range of protein-DNA complexes
  • plays a protective role in periodontitis through acetylation of DKK1
  • essential role for both KAT2A and retinoic acid (RA) signaling in early diencephalic development
  • plays important roles in multiple stages of T cell functions including development, clonal expansion, and differentiation
  • histone acetyltransferase essential for embryonic development, and required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF) signaling pathway in early embryoid bodies (EBs)
  • stabilizes pluripotency with control of transcriptional heterogeneity
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component part of the STAGA complex (SUPT3H-TAF9-KAT2A-TADA1-SUPT7L) that is a chromatin-acetylating transcription coactivator interacting with pre-mRNA splicing and DNA damage-binding factors
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with TADA2L
  • interacting with CHEK1 (function in the same pathway to regulate the transcription of cell-cycle genes and thus promote cell-cycle progression)
  • ADA2a and ADA2b
  • binds more avidly to RELA after phosphorylation on Ser 468, an event that is dependent on IKK activity
  • interacting with CDC6 (mediates acetylation and site-specific phosphorylation of CDC6, both necessary for the relocalization of the protein to the cell cytoplasm in the S phase, as well as to regulate its stability)
  • binds to the 5prime proximal regions of SYK and BTK genes, suggesting that gene expressions of SYK and BTK are regulated by KAT2A
  • NUT can interact with additional HAT enzymes such as KAT5 and KAT2A to induce the histone hyperacetylation on chromatin
  • WDHD1 having remarkable capability to regulate the stability of KAT2A proteins and thereby histone H3 acetylation
  • functional link between KAT2A and WDHD1 essential for KAT2A protein stability and histone H3 acetylation, but also a potential role of WDHD1 in cancer
  • DTL and WDHD1 play an essential role in the regulation of KAT2A protein stability
  • PTGES3 regulates both KAT2A acetylase and HSF1 DNA binding activities
  • inhibition of KAT2A protein catalytic activity by polyglutamine-expanded ATXN7
  • SUPT20H-mediated suppression of KAT2A ubiquitination most likely occurs via nuclear sequestration of KAT2A
  • KAT2A and EBF1 participate in regulation of PRKCQ gene expression in an opposite manner in immature B cells
  • MYC interacts with the human STAGA coactivator complex via multivalent contacts with the KAT2A and TRRAP subunits
  • LAMTOR5 promotes the migration of breast cancer cells through modulating microtubule acetylation mediated by KAT2A
  • KAT2A regulates osteogenic differentiation of mesenchymal stem cells by inhibiting NFKB1
  • ORC5 associates with the H3 histone acetyl transferase KAT2A, and this association enhances the chromatin-opening function of ORC5
  • regulated DKK1 expression by acetylation of Histone H3 lysine 9 (H3K9) and Histone H3 lysine 14 (H3K14) at its promoter region
  • KAT2A/KAT2B acetylation of PLK4 prevents centrosome amplification
  • link between KAT2A and the FGF signaling pathway and specific KAT2A-MYC partnerships in gene regulation during early differentiation
  • ERCC3 interacts functionally with KAT2A, a histone acetyltransferase (HAT) that belongs to the hSAGA and hATAC complexes
  • tight connection between GTFIIH1 and KAT2A that controls higher-order chromatin structure and gene expression
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    enhanced the proangiogenic potency of osteoporotic bone marrow-derived mesenchymal stem cells (BMSCs)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    may be an important new target for autoimmune disease therapy
    ANIMAL & CELL MODELS
    Gcn5l2-null mouse embryos died during embryogenesis