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FLASH GENE
Symbol ZFP36 contributors: mct/npt/pgu - updated : 18-07-2016
HGNC name zinc finger protein 36, C3H type, homolog (mouse)
HGNC id 12862
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestine   highly
Lymphoid/Immunespleen   highly
 thymus   highly
Nervousgangliasensory gangliadorsal root  
 nerve   highly
Reproductivefemale systemuteruscervix highly
 female systemplacenta  highly
Respiratorylung   highly
Skin/Tegumentskin     Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Endocrineislet cell (alpha,beta...)
Lymphoid/Immunemacrophage
Skin/Tegumentkeratinocyte Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
cell cycle     cell cycle, checkpoint
Text placenta
PROTEIN
PHYSICAL PROPERTIES basic
STRUCTURE
motifs/domains
  • Kruppel-associated box at the N-terminus
  • two C3H1-type zinc fingers
  • a basic proline-rich domain
  • one KRAB domain
  • potential phosphorylation sites including the sequence PSPTSPT
  • three tetraproline repeats
  • a serine-rich region
  • a serine-phenylalanine "SFS" and an "arginine element " (RRLPIF) at the carboxyl terminus
  • a nuclear localization signal (NLS)
  • a nuclear export signal (NES)
  • conserved C-terminal motif in ZFP36 that directly binds a central domain of CNOT1, a core subunit of the CCR4-NOT complex
  • conjugated MetalloP
    HOMOLOGY
    interspecies ortholog to murine tristetraprolin (Zfp-36)
    homolog to C.elegans y48g8ar.c
    Homologene
    FAMILY
  • Krüppel family of C2H2-type zinc finger protein
  • TIS11 family of early-response genes
  • zinc finger protein-36 family
  • CATEGORY regulatory , RNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text cytosolic in macrophages
    basic FUNCTION
  • inhibiting macrophage TNF-alpha production by destabilizing its mRNA
  • involved in regulating the response to growth factors
  • physiological regulator of GM-CSF mRNA deadenylation and stability
  • having a functional role of CCCH zinc finger genes in the regulation of macrophage activation
  • destabilizes a number of inflammatory mediators via its zinc finger-mediated interaction with AREs
  • AU-rich elements (ARE)-binding protein that promotes degradation of ARE-containing transcripts
  • involved in regulation of LATS2 transcript stability (may modulate the effect of this protein on cell proliferation)
  • involved in post-transcriptional regulation of BIRC3 expression
  • modulates macrophage inflammatory activity by destabilizing cytokine mRNAs
  • could control IL17-mediated inflammation
  • CCCH tandem zinc finger proteins that can bind to AU-rich elements in mRNAs and promote their decay
  • ZFAND5 and ZFP36 coordinately regulate many ARE-encoding proinflammatory genes at the level of mRNA decay
  • potential and hitherto unreported role of ZFP36 gene in kidney morphogenesis
  • RNA-binding protein that controls the inflammatory response by limiting the expression of several proinflammatory cytokines
  • ZFP36 plays an important role in RIPK1-dependent cell death in conditions where IAPs are depleted
  • regulates the expression of AU-rich element-containing mRNAs through promoting the degradation and repressing the translation of target mRNA
  • promotes translation repression and degradation of mRNAs containing AU-rich elements (AREs)
  • ZFP36, ZFP36L1, and ZFP36L2, regulates the production of growth factors and cytokines via destabilization of the respective mRNAs
  • both ZFP36 and ZFP36L1 influence keratinocyte cell cycle, differentiation, and apoptosis in a distinct manner
  • ZFP36, ZFP36L1, and ZFP36L2, play key roles in the post-transcriptional regulation of gene expression
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS immunity/defense
    text anti-pathogen response
    PATHWAY
    metabolism other
    signaling
    mRNA catabolism
    a component
    INTERACTION
    DNA
    RNA binding to AU-rich element in TNF-alpha mRNA
    small molecule metal binding,
  • Zn2+
  • protein
  • downregulates IL6 gene expression at the post-transcriptional level by targeting ARE elements in the 3prime UTR region
  • interaction between ZFP36 and CCL3 mRNA plays an important role in modulating localized inflammatory processes in tissues that are dissociated from the systemic manifestations of chronic inflammation
  • PRR5L associates with ZFP36 to accelerate ZFP36-mediated mRNA turnover and functionally links the control of ZFP36-regulated mRNA stability to MTORC2 activity (
  • general translational repressor DDX6 may cooperate with ZFP36 to regulate AU-rich elements (AREs)-mRNA translation
  • could bind to certain isoforms of another AU-rich element-binding protein, HNRNPD, as well as a related protein, laAUF
  • ZFAND5 competes with ZFP36 for association with AU-rich elements (AREs)-RNA, suppresses ZFP36-induced deadenylation, and interferes with the destabilizing effect of ZFP36 toward ARE-RNA
  • HNRNPF is a co-factor in a subset of ZFP36/BRF1-mediated mRNA decay
  • ZFP36 recruits eukaryotic initiation factor 4E2 (EIF4E2) to repress target mRNA translation
  • ZFP36 promotes the assembly of the death complex called Ripoptosome and induces RIPK1-dependent death
  • cell & other
    REGULATION
    induced by early response gene induced by growth factors and tumor promoters (tetradecanoyl phorbol acetate (TPA)
    insulin and growth factor
    Other localized by YWHAx (14-3-3) genes to the cytoplasm
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    expression restricted to the cells in the synovial lining layer in rheumatoid arthritis
    constitutional     --over  
    its overexpression reduced the expression level of LATS2)
    Susceptibility
  • to rheumatoid arthritis (RA) in African-Americans
  • to Graves ophthalmopathy
  • Variant & Polymorphism SNP , other
  • polymorphisms increasing the risk of rheumatoid arthritis (RA) in African-Americans
  • rs1057745 and rs11083522 in ZFP36 were associated with Graves ophthalmopathy
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    mice deficient in ttp