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FLASH GENE
Symbol KDM4A contributors: mct - updated : 17-08-2015
HGNC name lysine (K)-specific demethylase 4A
HGNC id 22978
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one JMJN domain
  • one JMJC domain, containing an internal retinoblastoma-binding protein 2 (RBBP2)-like sequence
  • two leukemia-associated protein/plant homeodomain (LAP/PHD) zinc fingers
  • two Tudor domains
  • conserved dual PHD domains
  • a NID (NCOR1 interaction domain)
  • HOMOLOGY
    interspecies homolog to yeast S.cerevisiae 90,2 kDa zinc finger protein
    homolog to murine Jmjd2a (93.2pc)
    Homologene
    FAMILY
  • JHDM3 histone demethylase family
  • KDM4 histone demethylase subfamily
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome,euchromosome
    text
  • normally locates in euchromatin
  • protein levels were highest in G1/S, decreased through S phase, and reached their lowest levels during G2/M
  • basic FUNCTION
  • required to recognize and demethylate trimethylated histone tails (converting specific trimethylated histone residues to the dimethylated form), a reaction important for gene regulation
  • mediating repression of E2F-regulated promoters
  • involved in cell proliferation and in oncogenesis
  • selectively repressing the expression of the ASCL2 gene
  • have a role of transcriptional repressor
  • reversed trimethylated H3-K9/K36 to di- but not mono- or unmethylated products
  • potentiating RB-mediated repression of E2F-regulated promoters and playing an important role in cell proliferation and oncogenesis
  • generates different methylated states at the same lysine residue provides a mechanism for fine-tuning histone methylation
  • role for the JMJD2A/KDM4A H3K9/36 tridemethylase in cell cycle progression
  • regulates DNA replication by antagonizing CBX3 and controlling chromatin accessibility
  • H3K9-specific demethylating enzyme clearly required to facilitate the POU5F1-mediated derepression of the stem cell-related microRNAs
  • showed a degree of flexibility with regard to localization and demethylation frequency depending on the guide proteins to which it was fused
  • KDM4A, KDM4B, KDM4C, catalyze demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2)
  • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • KDM4A and KDM4D, form complexes with ligand-bound AR
  • INTERACTION
    DNA binding
    RNA
    small molecule metal binding, cofactor,
  • Zn2+
  • Fe2+ (one ion per subunit)
  • protein
  • methylated histone H4-K20
  • HDAC1, HDAC2, HDAC3, RB and NCOR1
  • the trimethylated histone H3-Lys4 via the 2 Tudor domains
  • interacts with the N-terminal region of NCOR1 through a small NID (NCOR1 interaction domain), and together with NCOR1 could play a role in repressing ASCL2 expression in various tissues
  • demethylates H3K9me3 more efficiently and rapidly when it is tagged with CBX5
  • Cullin 1 interacted with KDM4A and contributed to ubiquitination and turnover
  • FBXL4 interacted with KDM4A and regulated protein turnover
  • KDM4A cooperated with ETV1 to increase expression of yes associated protein 1 (YAP1), a Hippo pathway component that itself was associated with prostate tumor aggressiveness
  • PSMD10 is a novel downstream effector of KDM4A
  • cell & other
    REGULATION
    Other its degradation is regulated by the proteasome, and involves at least two F-box proteins, FBXL4 and FBXW2
    ubiquitinated and degraded by the 26S proteasome
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    leads to altered replication timing and faster S phase progression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS