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FLASH GENE
Symbol KDM8 contributors: mct/pgu - updated : 08-11-2017
HGNC name lysine (K)-specific demethylase 8
HGNC id 25840
Location 16p12.1      Physical location : -
Synonym name
  • JmjC domain-containing protein 5
  • histone lysine demethylase
  • jumonji domain containing 5
  • Synonym symbol(s) FLJ13798, JMJD5
    EC.number 1.14.11.27
    DNA
    TYPE functioning gene
    STRUCTURE 18.28 kb     8 Exon(s)
    regulatory sequence Binding site
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 2481 - 416 - 2006 16858412
    8 - 2531 - 454 - 2010 20457893
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a nuclear hormone receptor binding motif LXXL located in the N-terminal region , N-terminal domain that is essential for the nuclear localization of KDM8 and its normal enzymatic function towards substrates in the nucleus
  • a JmjC domain
  • a functional bipartite nuclear localization signal (NLS)
  • a chromosome region maintenance 1 (CRM1)-dependent nuclear export signal (NES)
  • HOMOLOGY
    Homologene
    FAMILY
  • JmjC family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • mainly localized in the nucleus of cells
  • partially accumulates on mitotic spindles during mitosis, and depletion of KDM8 results in significant mitotic arrest, spindle assembly defects, and sustained activation of the spindle assembly checkpoint
  • basic FUNCTION
  • putative histone lysine demethylase
  • contribute to genome stability
  • important cell cycle regulator
  • required for G2/M phase cell cycle progression
  • is capable of up-regulating CCNA1 transcription by demethylating H3K36me2 located in the cyclin A1 coding region
  • plays an interchangeable role in the timing mechanisms of plants and animals despite their highly divergent evolutionary paths
  • demethylate histone H3 dimethylated at lysine 36 (H3K36me2)
  • physiologically moderates embryonic cell proliferation through the epigenetic control of CDKN1A expression
  • is a post-translational co-repressor for NFATC1 that attenuates osteoclastogenesis
  • histone demethylase that specifically removes methyl moieties from dimethylated lysine 36 on histone H3 and exerts a pro-proliferative effect on breast cancer cells
  • essential during embryonal development and repressor of TP53 expression
  • may perform an oncogenic function by suppressing p53 expression, thereby relieving TP53-imposed breaks on cell cycling and survival
  • participates in roles independent of histone demethylation and may function as a protein hydroxylase given its structural homology with HIF1AN and JMJD6
  • participate in circadian rhythm regulation, embryological development, osteoclastogenesis and tumorigenesis
  • JmjC-domain-containing histone demethylase with enzymatic activity towards H3K36me2
  • might function as a protein hydroxylase
  • Jumonji C domain-containing demethylase/hydroxylase shown to be essential in embryological development, osteoclastic maturation, circadian rhythm regulation and cancer metabolism
  • reported to be involved in epigenetic regulation of gene expression in the nucleus
  • plays likely an important role in regulating mitotic progression, probably by modulating the stability of spindle microtubules
  • regulate several transcriptional factors to maintain hepatocyte function
  • regulates H3K36 di-methylation, it is required at late stages of double strand break repair mediated by homologous recombination, and is required for late steps of homologous recombination and genome integrity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • KDM8/CDKN1A (p21) axis is essential to maintaining the short G1 phase which is critical for pluripotency in hESCs
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • SUV39H1 and SETDB1 interact with JMJD5 in the N-terminal region, indicating complex regulation of JMJD5
  • physiologically moderates embryonic cell proliferation through the epigenetic control of CDKN1A expression
  • regulates NFATC1 protein stability
  • induced the association of hydroxylated NFATC1 with VHL, thereby presumably facilitating proteasomal degradation of NFATC1 via ubiquitination
  • interaction between KDM8 and the core histone octamer proteins indicated that the histone proteins could be potential substrates for KDM8
  • KDM8/PKM interaction resides at the intersubunit interface region of PKM, which hinders PKM tetramerization and blocks pyruvate kinase activity
  • is a novel binding partner of TP53 and it functions as a positive modulator of cell cycle and cell proliferation mainly through the repression of TP53 pathway
  • important role for KDM8 in breast cancer through the regulation of SNAI1
  • interaction of KDM8 with HBx facilitates HBV replication through the hydroxylase activity of KDM8
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in several types of cancer, breast, thyroid, adrenal, bladder, uterine, and liver
    tumoral       loss of function
    in MCF7 cells leads to cell cycle arrest
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS