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FLASH GENE
Symbol ZBTB16 contributors: mct/pgu - updated : 13-12-2023
HGNC name zinc finger and BTB domain containing 16
HGNC id 12930
Corresponding disease
APLZF acute promyelocytic leukemia (APL), zinc finger
Location 11q23.2      Physical location : 113.930.430 - 114.121.394
Synonym name
  • zinc finger protein 145 (Kruppel-like, expressed in promyelocytic leukemia)
    • Synonym symbol(s) PLZF, ZFP145, ZNF145, ZFP14
    DNA
    TYPE functioning gene
    STRUCTURE 197.01 kb     7 Exon(s)
    regulatory sequence Promoter
    Binding site
    text structure ZBTB16 promoter-binding sites revealed that it represses transcription factors involved in normal myeloid differentiation
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 splicing 8494 74.27 673 - 2016 26676652
  • a 7 exons variant
  • lacking exon 2
  • encoding for the same product as variant 2
  • also called AS-Ia
    • 7 splicing 8754 - 673 stomach 2016 26676652
  • splicing exon 1, long 5'UTR
  • lacking BTB/POZ domain
  • also called AS-II
    • 7 splicing 8375 - 673 testis 2016 26676652
  • splicing exon 1, long 5'UTR
  • lacking BTB/POZ domain
  • also called AS-III
    • 5 splicing 8240 - 644 heart, placenta and stomach 2016 26676652
  • splicing exon 1, long 5'UTR
  • lacking BTB/POZ domain
  • also called AS-IV
    • 7 splicing 8400 74.27 673 - 2016 26676652
  • a 7 exons variant
  • lacking exon 1
  • encoding for the same product as variant 1
  • also called AS-Ib
    		•
    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,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    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
  • is essential for nearly all of the unique characteristics of NKT cells including their rapid and potent response to antigen
  • stably repressed in non-innate T cells and TCR-mediated signaling was not sufficient to induce PLZF in conventional T cells
  • ZBTB16 acts as a downstream transcriptional regulator of SP7
  • associated with active enhancers, appears to restrain their activity as an epigenetic gatekeeper of hematopoietic aging
  • is a key factor in inhibiting differentiation of spermatogonial progenitor cells (SPCs)
  • ZBTB16 may play an important role in modulating the odontoblastic differentiation of dental pulp stem cells (DPSCs) and act as a regulator of SP7
    • 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
  • ZBTB16 as an interacting protein of NLRP7
  • KAT2A regulates ZBTB16 through acetylation, mediates osteogenic differentiation, and affects orthodontic tooth movement
    • 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
  • represents a promising pleiotropic candidate node for metabolic syndrome
    • Marker
  • can be useful as a late marker of osteoblastic differentiation.
  • could be a promising tumor biomarker for Gallbladder cancer (GBC)
    • Therapy target
    SystemTypeDisorderPubmed
    osteoarticularboneostéoporosis
    Super enhancers targeting ZBTB16 in osteogenesis protect against osteoporosis
    cancerdigestiveliver
    potential therapeutic target in Gall bladder cancer
    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