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FLASH GENE
Symbol ZBTB16 contributors: mct/pgu - updated : 27-03-2013
HGNC name zinc finger and BTB domain containing 16
HGNC id 12930
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/EquilibriumearinnercochleaCortihighly Homo sapiensAdult
Nervousbrain   highly Homo sapiensAdult
Reproductivemale systemprostate  highly
Respiratorylung   lowly
Urinarykidney   lowly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  lowly
Connectiveadiposebrown highly Homo sapiensAdult
Muscularstriatumskeletal highly
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticprogenitor cell
not specificadipocyte Homo sapiensAdult
Reproductivespermatocyte
cell lineage
cell lines early myeloid cell lines
fluid/secretion
at STAGE
Text in limb bud (anterior to posterior patterning in axial and appendicular skeleton)
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a BTB/POZ (zinc finger N-terminal) interaction domain
  • nine krueppel-type C-terminal zinc finger motifs
  • C terminal RD2 domain
  • conjugated MetalloP
    HOMOLOGY
    interspecies homolog to murine Zbtb16 (96.73 pc)
    homolog to rattus Zbtb16 (96.14 pc)
    Homologene
    FAMILY
  • zinc finger protein family
  • CHC2 type, krueppel-like
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,chromatin/chromosome
    text with MTDH, colocalize to nuclear bodies containing histone deacetylases, which are known to promote ZBTB16-mediated repression
    basic FUNCTION
  • recruiting nuclear histone deacetylase through nuclear corepressor N-COR
  • co-expression of ZBTB16 and RB1 results in enhancement of transcriptional repression of ZBTB16 and E2F/Rb target genes, indicating functional co-operation between the two proteins
  • DNA sequence-specific transcriptional repressor
  • playing a key role in human myeloid development
  • regulator of HOX gene expression and of myeloid maturation
  • spermatogonia-specific transcription factor in the testis that is required to regulate self-renewal and maintenance of the stem cell pool
  • playing a significant stimulatory role in megakaryocytic development, seemingly mediated in part by induction of TpoR expression at transcriptional level
  • activates CXCR4 translation in megakaryopoiesis
  • may be involved in a general mechanism in the regulation of hematopoiesis, linking lineage-specific transcription factors, miRNAs and key mRNA targets, particularly growth factor/chemokine receptors
  • also required for stem-cell self-renewal and maintenance in adult male germ cells
  • invariant natural killer T cells -specific transcription factor that is necessary for full functionality (
  • during homeostasis, restricts proliferation and differentiation of cord blood-derived myeloid progenitors to maintain a balance between the progenitor and mature cell compartments
  • may play a role in differentiation of hematopoietic progenitors
  • regulates the expression of genes involved in cell growth and apoptosis including c-myc
  • sufficient to promote T cell effector functions and ZBTB16 acts independently of SAP- and Fyn-mediated signaling pathways
  • opposes MTOR activity and define a cellular signaling network controlling spermatogonial progenitor cells (SPC) homeostasis whereby MTOR integrates mitogenic signals received by SPCs and determines their sensitivity to self-renewal stimuli
  • role for ZBTB16-mediated DDIT4 expression in inhibiting MTOR activation in spermatogonial progenitor cells
  • is remarkable in that it is a transcription factor capable of inducing an effector program in the absence of T cell agonist interactions or cell division
  • transports CUL3 to the nucleus, where the two proteins are associated within a chromatin-modifying complex
  • regulates the expression of a surprisingly small set of genes, many with known immune functions, and of a limited number of genes essential for NKT cell function
  • implicated as a novel determinant of substrate utilization in brown adipocytes and of adiposity
  • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, transcription
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • GATA2 modifying transactivation capacity
  • interacting with GATA1, activating thrombopoietin receptor and inducing megakaryocyte development
  • interacting with CRMP1 and GNE
  • upstream regulator of Runx2/CBFA1
  • interacting with ZBTB32 (ZBTB16 differentially participate in the regulation of osteoblastic differentiation via the BMP2 and CBFA1 signaling pathways, respectively)
  • ZBTB16 (PLZF) specifically bound to GNAO1
  • interacts with RB1 (interaction between ZBTB16 and RB1 is mediated through the RB1 pocket and the region of ZBTB16 that lies between its transcriptional repression (poxvirus and zinc-finger, POZ) and DNA-binding (zinc-finger) domains)
  • ZBTB16-mediated control on KIT expression in CD34(+) cells and early erythropoiesis
  • interacting protein of MTDH (interact in mammalian cells via the N- and C termini of MTDH and a region C terminal to the RD2 domain of ZBTB16)
  • interacting with stress-induced cytokines that can act by interfering with the capacity of ZBTB16 to inhibit proliferation and differentiation
  • repressed CEBPA transcription but did not bind to its promoter, indicating indirect regulation
  • transcriptional target for the CUX1 repressor (the novel genetic relationship between CUX1 and PLZF could be of relevance to human diseases, such as leukemia)
  • mechanistically, SALL4 sequesters ZBTB16 to noncognate chromatin domains to induce expression of KIT, a target of ZBTB16-mediated repression required for differentiation
  • prominently associated with CUL3, an E3 ubiquitin ligase previously shown to use BTB domain-containing proteins as adaptors for substrate binding
  • USP37 interacted with ZBTB16/RARA through the ZBTB16 moiety and sustained ZBTB16/RARA steady state levels
  • potential role for SLAMF6 in the induction of ZBTB16
  • RARA-ZBTB16 acts as a modifier oncogene that subverts differentiation in the granulocytic lineage by associating with CEBPA and inhibiting its activity
  • HOXA5, HOXC5, HOXB5 interacts with promyelocytic leukemia zinc finger (ZBTB16) biochemically and genetically to restrict SHH expression
  • cell & other
    REGULATION
    repressed by FHL2
    ASSOCIATED DISORDERS
    corresponding disease(s) APLZF
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with RARA, in acute promyelocytic leukaemia and a translocation t(11;17)(q23;21)
    Susceptibility to autism spectrum disorder
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Plzf-deficient mice (luxoid, Zbtb16Lu) had severe patterning defects of the limbs and the axial skeleton
  • heterozygous mutant (luxoid.Zbtb16(LU)/J) mice deficient in Zbtb16 have hearing and responses to acoustic trauma similar to their wild type littermates but are unable to generate conditioning-induced protection from acoustic trauma