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FLASH GENE
Symbol KDM5B contributors: mct - updated : 05-04-2016
HGNC name lysine (K)-specific demethylase 5B
HGNC id 18039
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
27 splicing 6393 - 1544 - 1999 10336460
three cysteine-rich zinc-binding PHD/LAP, a DNA-binding domain also found in the drosophila dead ringer (dri) gene,five putative nuclear localization signals
- - splicing 7500 190.1 1681 - 1999 10336460
three DNA-binding zinc-finger domains and two bipartite nuclear localization signals
- splicing 9780 179.7 1580 - 1999 10336460
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Reproductivefemale systembreastmammary gland  
 female systemovary  highly
 male systemtestis  highly
 male systemprostate   
cells
SystemCellPubmedSpeciesStageRna symbol
Reproductivespermatogonia
cell lineage
cell lines breast cancer cell lines highly
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta lowly
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