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FLASH GENE
Symbol KDM5B contributors: mct - updated : 05-04-2016
HGNC name lysine (K)-specific demethylase 5B
HGNC id 18039
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • first PHD domain (PHD1 AAs 306-360) is located at the N-terminus and is important for both histone demethylase activity and histone-tail recognition of KDM5B , and may help maintain KDM5B at target genes to mediate the demethylation activities of KDM5B
  • first and third, but not the second, PHD fingers of KDM5B possess histone binding activities
  • three DNA-binding PHD/LAP zinc finger motifs
  • a specific DNA-binding motif found in Drosophila protein dri and other conserved motifs
  • a PLU domain
  • two bipartic nuclear localization signals (NLS)
  • a JmjC domain containing the catalytic pocket for demethylation
  • a Bright/Arid domain and zinc-finger-like domain are for protein/DNA and protein/protein interactions, a potential DNA-binding domain of KDM5B
  • 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)
  • mono polymer polymer
    HOMOLOGY
    intraspecies homolog to homolog RBBP2
    Homologene
    FAMILY ARID family of DNA binding proteins
    CATEGORY regulatory , transcription factor , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • testis-cancer antigen regulating genes expression in breast cancer
  • acting as a transcriptional co-repressor of two unrelated developmental transcription factors(BF-1 and PAX9)interacting with members of the groucho co-repressor family, and may be having a role in groucho-mediated transcriptional repression
  • playing a role in in meiotic transcription, which may be restricted to certain meiotic stages and may be mediated by the ability of this protein to associate with the chromatin
  • demethylase capable of removing three methyl groups from histone H3 lysine 4 and up-regulated in prostate cancer
  • regulates the AR transcriptional function
  • regulates cell cycle control genes in cancer and is expressed in the early epiblast
  • specifically demethylates lysine 4 of histone H3 (meH3K4), thereby repressing gene transcription
  • playing a role in the choice between proliferation and differentiation during development
  • crucial role in H3K4me3 demethylation
  • iron- and - alpha ketoglutarate-dependent dioxygenase
  • KLF10 and JARID1B may cooperate to suppress tumorigenesis by enhancing TGFB signaling
  • KLF10 and JARID1B cooperate in repressing SMAD7 transcription and thereby antagonize skin cancer development
  • potentially activates self-renewal-associated gene expression by repressing cryptic initiation and maintaining an H3K4me3 gradient important for productive transcriptional elongation
  • functional contribution of its overexpression with concomitant epigenetic dysregulation in cancer progression
  • play a critical role in the development of breast cancer
  • essential role for KDM5B-mediated transcriptional control during embryonic stem cell differentiation
  • KDM5A and KDM5B demethylases are tumor-suppressor network controlling cellular senescence
  • regulate the expression of genes involved in cell cycle progression
  • demethylates H3K4, is important for ES cell differentiation and presents a barrier to the reprogramming process
  • KDM5B and KDM1A, another H3K4 demethylase, co-regulate H3K4 methylation at active promoters but they retain distinct roles in demethylating gene body regions and bivalent genes
  • positively regulates mammary ductal development through both extrinsic and cell-autonomous mechanisms
  • removes methyl residues from methylated lysine 4 on histone H3 lysine 4 (H3K4)
  • pivotal role in stimulating metastatic behaviors of HCC cells
  • is a key component of a potent epigenetic switch that controls mesenchymal cell fate into myogenic and osteogenic lineages
  • 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, chromatin organization, remodeling
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text chromatin/chromosome structure
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA DNA binding
    RNA
    small molecule metal binding,
    Zn2+
    protein
  • interactging with brain factor-1 (BF-1) and paired box 9 (PAX9), both of which are developmental transcription factors,via a novel conserved sequence motif (Ala-X-Ala-Ala-X-Val-Pro-X4-Val-Pro-X8-Pro, termed the VP motif), because deletion or site-directed mutagenesis of this motif in either protein abolishes PLU-1 interaction
  • interacting with CBX4 (C-terminal region, including the COOH box, was required for the interaction with the N-terminus of KDM5B) (
  • KLF10 interacts with JARID1B (the repression domains of KLF10 bind to the C-terminus of JARID1B)
  • cooperates with KLF10 in repressing the SMAD7 promoter
  • downstream NANOG target and critical for embryonic stem cell self-renewal (
  • repress the expression of the KAT5 gene through its H3K4 demethylation on the promoter)
  • KDM5B repressed the expression of CCL14, an epithelial derived chemokine, suppressing the angiogenic and metastatic potential of breast cancer cells
  • FOXP3 orchestrates H4K16 acetylation and H3K4 trimethylation for activation of multiple genes by recruiting KAT8 and causing displacement of KDM5B
  • TFAP2C and MYC associate with distinct domains of KDM5B and the TFAP2C C-terminal 270 AAs are required for MYC and KDM5B interaction
  • is modulated by RNF4, an E3 ubiquitin ligase that targets SUMO-modified proteins to proteasomal degradation
  • associates with components of the nucleosome remodeling and deacetylase (NuRD) complex and may cooperate with the histone deacetylase 1 (HDAC1) in gene repression
  • MYCN repressed KDM5B expression by direct binding to the Sp1-binding site-enriched region of the KDM5B gene promoter, and cell proliferation assays showed that transcriptional repression of KDM5B reduced neuroblastoma cell proliferation
  • KDM5B is required for efficient DSB repair and for the recruitment of XRCC6 and BRCA1, the essential component of nonhomologous end-joining and homologous recombination, respectively
  • required for GATA3 recruitment to the FOXA1 promoter to activate FOXA1 expression
  • IKZF1 represses transcription of the histone H3K4 demethylase, JARID1B (KDM5B)
  • IKZF1 and HDAC1 regulate the epigenetic signature in leukemia, via regulation of KDM5B transcription
  • cell & other
    REGULATION
    induced by ERBB2 in breast cancer cell libne
    ASSOCIATED DISORDERS
    corresponding disease(s) MRT65
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer cell lines
    tumoral     --over  
    in prostate cancer tissues, compared with benign prostate samples
    tumoral     --low  
    in melanomas
    tumoral   amplification    
    in breast cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    potential target for breast cancer treatment
    ANIMAL & CELL MODELS