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FLASH GENE
Symbol ZFP36L2 contributors: mct/npt - updated : 11-06-2020
HGNC name zinc finger protein 36, C3H type-like 2
HGNC id 1108
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a distinguishing putative zinc finger domain
  • a repeating Cys-His motif (two C3H1-type zinc fingers)
  • a tandem zinc finger (TZF) domain binding to the class II AU-rich element (ARE) in the 3' untranslated region (3' UTR) of target mRNAs and promotes their deadenylation and degradation
    • conjugated MetalloP
    HOMOLOGY
    interspecies homolog to murine Zfp36l2
    Homologene
    FAMILY
  • tristetraprolin family of CCCH tandem zinc finger proteins
  • TIS 11 family of early response genes
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    text shuttle between the nucleus and cytoplasm
    basic FUNCTION
  • functioning in regulating the response to growth factors
  • having a functional role of CCCH zinc finger genes in the regulation of macrophage activation (Liang 2008)
  • role for ZFP36L1 and ZFP36L2 during thymocyte development and in the prevention of malignant transformation
  • AU-rich element binding protein that is involved in RNA metabolism and definitive hematopoiesis
  • ZFP36, ZFP36L1, and ZFP36L2, regulates the production of growth factors and cytokines via destabilization of the respective mRNAs
  • destabilizes AU-rich element (ARE)-containing transcripts and has been implicated in female fertility
  • ZFP36L1 and ZFP36L2 inhibit cell proliferation in a CCND-dependent and TP53-independent manner
  • ZFP36L2 promotes the destruction of AU-rich element-containing transcripts
  • is a cell cycle-regulated CCCH protein, the abundance of which is regulated post-translationally at the respective stages of the cell cycle
  • is a key protein that controls S-phase progression in the case of genome instability
  • ZFP36L1 and ZFP36L2 act redundantly in myogenesis
  • ZFP36, ZFP36L1, and ZFP36L2, play key roles in the post-transcriptional regulation of gene expression
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
  • preferentially binds to messenger RNAs that are induced or maintained at high expression levels during terminal erythroid differentiation and negatively regulates their expression levels
    • small molecule metal binding,
  • Zn2+
    • protein
  • interact with AU-rich elements in the 3prime untranslated region of mRNA, which leads to mRNA degradation and translational repression
  • lack of the physiological down regulation of LHCGR mRNA levels by ZFP36L2 in the ovaries is associated with anovulation and oocyte meiotic arrest
  • ZFP36L2, associated previously only with female fertility and hematopoiesis, regulates REST mRNA stability
  • in developing B lymphocytes, the RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion
  • in addition to controlling the timing of proliferation at thymic beta-selection, posttranscriptional control by ZFP36L1/L2 limits DNA damage responses, which are known to promote thymocyte differentiation
  • ZFP36L2 protein was eliminated after release from M phase, and ZYG11B-based E3 ligase plays a role in its polyubiquitination in interphase
  • ZFP36L2 could be transactivated by RUNX1, which subsequently induced cell-cycle arrest and apoptosis of leukemia cells
    • cell & other
    REGULATION
    induced by growth factors and tumor promoters tetradecanoyl phorbol acetate (TPA)
    a broad variety of growth factors and cytokines, and by scratch wounding
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    dysregulation of ZFP36L2 function is associated with the pathogenesis of certain types of leukemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene candidate TP53 target gene that may be part of the network of genes responsible for TP53-dependent apoptosis
    Marker
    Therapy target
    ANIMAL & CELL MODELS