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FLASH GENE
Symbol KDM5A contributors: SGE/mct - updated : 05-04-2016
HGNC name lysine (K)-specific demethylase 5A
HGNC id 9886
Location 12p13.33      Physical location : 389.222 - 498.620
Synonym name
  • retinoblastoma binding protein 2
  • histone H3 lysine 4 demethylase
  • Jumonji, AT rich interactive domain 1A (RBBP2-like)
  • Jumonji/ARID domain-containing protein 1A
  • histone demethylase JARID1A
  • Synonym symbol(s) RBP2, RBBP2, JARID1A
    EC.number 1.14.11.-
    DNA
    TYPE functioning gene
    STRUCTURE 109.40 kb     28 Exon(s)
    regulatory sequence alternative promoter
    MAPPING cloned Y linked N status confirmed
    regionally located same locus than D12S98
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    29 - 10932 - 1641 - 2007 17573780
    28 - 10835 - 1690 - 2007 17573780
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Cardiovascularheart    
    Nervousbrain    
    Reproductivemale systemprostate   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Lymphoid    
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a DNA binding domain
  • a AT-rich interaction domain (ARID), required for KDM5A demethylase activity in cells
  • three PHD reader domains, commonly recognized as chromatin recruitment modules
  • three PHD-type zinc fingers, and PHD1 preferentially recognizes unmethylated H3K4 histone tail, product of KDM5A-mediated demethylation of tri-methylated H3K4 (H3K4me3)
  • atypical insertion of a DNA-binding ARID domain and a histone-binding PHD domain into the Jumonji domain, which separates the catalytic domain into two fragments (JmjN and JmjC)
  • HOMOLOGY
    interspecies homolog to murine Rbbp2
    homolog to C.elegans ZK593.4
    Homologene
    FAMILY
  • JARID1 histone demethylase family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • having perhaps a role in transcriptional regulation
  • acting as an histone demethylases specific for di- and trimethylated histone 3 lysine 4 (H3K4)
  • playing a potential role for in NR-mediated transcription
  • increased histone acetylation by inhibiting histone deacetylase 1 function and enhanced transcription by CLOCK-ARNTL in a demethylase-independent manner
  • has a nonredundant role in circadian oscillator function
  • its lysine demethylase activity is dispensable for normal circadian rhythms in mammalian cells, its HDAC-inhibiting function appears to be necessary for proper oscillator function
  • KDM5A and KDM5B demethylases are tumor-suppressor network controlling cellular senescence
  • critical role of H3K4 demethylation by KDM5A in the transcriptional silencing of genes that are suppressed by RB family members in differentiated cells
  • is likely involved in the transformation of gonocytes into spermatogonial stem cells by transcriptional regulation of specific genes via H3K4 histone modification
  • retinoblastoma binding protein KDM5A removes methyl marks from lysine 4 of histone H3 (H3K4)
  • is a direct repressor of metabolic regulatory genes, thus explaining the compensatory role of KDM5A deletion in restoring mitochondrial function and differentiation
  • enzymatic activity of the KDM5 family required to be the linked JmjN-JmjC domain coupled with the immediate C-terminal helical zinc-binding domain, providing structural characterization of the linked JmjN-JmjC domain for the KDM5 family
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text demethylation regulated by the JARID1 family plays an important role during development
    PATHWAY
    metabolism
    signaling
    a component
  • component of the Notch/RBPJ repressor complex
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • binding to RB1 (viral protein-binding domain) and RBTN2/LMO2
  • not only binds to nuclear receptors (NRs) but also enhances the transcription mediated by them (interacts with the DNA-binding domains of NRs and potentiates NR-mediated transcription in an AF-2-dependent manner)
  • associated with MORF4L1 complex to maintain reduced H3K4 methylation at transcribed regions, which may ensure the transcriptional elongation state
  • interacting with RBPJ
  • coactivates CLOCK-ARNTL–mediated transcription of PER genes
  • cooperated with E2F4 to promote a state of deepened repression at cell cycle genes during differentiation
  • chromatin regulators EP300, KDM5A, KDM6A and KDM6B cooperate with KLF4 in promoting the transcription of POU5F1
  • KDM5A upregulated expression of CCND1 and CCNE1 while suppressing the expression of cyclin-dependent kinase inhibitor p27 (CDKN1B), each contributing to KDM5A-mediated cell proliferation
  • is physically and functionally associated with two histone deacetylase complexes
  • genes commonly regulated by both KDM5A and CHD4 were categorized as developmentally regulated genes
  • is a RB1-interacting protein counteracting RB1 role in promoting differentiation
  • activation of mitochondrial function by the mitochondrial biogenesis regulator PPARGC1A a coactivator of the KDM5A target genes, is sufficient to override the differentiation block
  • cell & other
    REGULATION
    Other regulated by its reader domain through a positive-feedback mechanism
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with NUP98 in acute myeloid leukaemia
    tumoral fusion      
    of NUP98 to KDM5A (t(11;15)(p15;q35)in acute megakaryoblastic leukemia (AMKL)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in Jarid1a-/- mouse fibroblasts, the Per2 promoter region showed an increased abundance of H3K4me3