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FLASH GENE
Symbol ZBTB4 contributors: SGE/mct - updated : 28-06-2022
HGNC name zinc finger and BTB domain containing 4
HGNC id 23847
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one BTB/POZ domain, POZ domain
  • 6 C2H2-type zinc fingers
  • Kaiso-like zinc fingers
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Zbtb4 (88.6pc)
    homolog to murine Zbtb4 (89.2pc)
    intraspecies homolog to ZBTB33
    Homologene
    FAMILY Kaiso-like proteins family
    CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • may be involved in transcriptional regulation
  • able to repress transcription in a methyl-dependent manner, yet their tissue-specific expression pattern suggests nonoverlapping functions
  • represses transcription of CDKN1A and controls the cellular response to TP53 activation
  • epigenetic regulator with high affinity for methylated CpGs that localizes at pericentromeric heterochromatin and is frequently downregulated in cancer
  • is a transcriptional repressor that regulates the cell cycle, including the apoptotic response to amyloid beta
  • is an essential component in maintaining genomic stability in mammals
  • ZBTB4 exhibited a tumor suppressive role in Ewing sarcoma (ES) possibly by reducing Survivin expression
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • homodimer or heterodimerizing with ZBTB38 (Filion 2006)
  • INTERACTION
    DNA bind methylated DNA
    RNA
    small molecule metal binding,
  • ions Zn2+
  • protein
  • bind methylated CGCGs through its three Kruppel-like C2H2 zinc fingers
  • associates with the Sin3/histone deacetylase co-repressor and represses expression of CDKN1A as part of a heterodimeric complex with ZBTB17
  • shares with ZBTB33 the ability to bind both methylated DNA and the KBS (Kaiso binding site)
  • with CDKN1A may have critical oncogenic functions independent of the TP3 status of a cell
  • ZBTB4 and ZBTB38 can bind methylated DNA in a sequence-specific manner, and they may use a mode of binding common to other zinc-finger proteins
  • cell & other
    REGULATION
    Other phosphorylated by HIPK2 and down-regulated (Yamada 2009)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in advanced stages of multiple tumours
    tumoral     --over  
    high-expressed ZBTB4 in colorectal cancer (CRC) tissues may develop a better prognosis
    Susceptibility to variation of age-at-onset of Alzheimer's disease
    Variant & Polymorphism other Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    could serve as a potential therapeutic target for CRC treatment
    cancerhemopathy 
    ZBTB4/Survivin axis might serve as a therapeutic target for Ewing sarcoma (ES)
    ANIMAL & CELL MODELS
  • primary cells isolated from Zbtb4-/- mice exhibited diminished mitotic checkpoint activity, increased mitotic defects, aneuploid cells marked by a specific transcriptional signature, and increased genomic instability