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FLASH GENE
Symbol ZFP36 contributors: mct/npt/pgu - updated : 18-07-2015
HGNC name zinc finger protein 36, C3H type, homolog (mouse)
HGNC id 12862
Location 19q13.1      Physical location : 39.897.486 - 39.900.045
Synonym name
  • tristetraprolin
  • protein TIS11A
  • growth factor-inducible nuclear protein NUP475
  • G0/G1 switch regulatory protein 24
  • Synonym symbol(s) TIS11, TTP, GOS24, NUP475, EVI24, G0S24, RNF162A, G0S24
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 2.00 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence cytosine-phosphate-guanine/HTF
    text structure
  • a CpG island suggesting expression in the germ line
  • serum response element
  • MAPPING cloned Y linked N status provisional
    Physical map
    FLJ45909 19q13.2 FLJ45909 protein SIRT2 19q13 sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae) NFKBIB 19q13.1 nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta LOC388539 19 LOC388539 SARS2 19q13.2 seryl-tRNA synthetase 2 MRPS12 19q13.11 mitochondrial ribosomal protein S12 FBXO26 19q13.2 F-box only protein 26 FBXO27 19q13.2 F-box only protein 27 LOC390928 19 similar to RIKEN cDNA C330005M16 LOC284321 19q13.2 hypothetical LOC284321 PAK4 19q13.2 p21(CDKN1A)-activated kinase 4 LOC342897 19q13.2 similar to F-box only protein 2 SYCN 19q13.2 syncollin IL28B 19q13.13 interleukin 28B (interferon, lambda 3) LOC390929 19 similar to Methionine-R-sulfoxide reductase (Selenoprotein X 1) (HSPC270) IL28A 19q13.13 interleukin 28A (interferon, lambda 2) IL29 19q13.13 interleukin 29 (interferon, lambda 1) KIAA1484 GMFG 19p13.2-p12 glia maturation factor, gamma FLJ10211 19q13.2 hypothetical protein FLJ10211 PD2 19q13.1 hypothetical protein F23149_1 Intersex 19q13.2 homolog of Drosophila Intersex ZFP36 19q13.1 zinc finger protein 36, C3H type, homolog (mouse) CLG 19q13.2 likely ortholog of mouse common-site lymphoma/leukemia GEF RPS16 19q13.1 ribosomal protein S16 SUPT5H 19q13 suppressor of Ty 5 homolog (S. cerevisiae) TIMM50 19q13.2 translocase of inner mitochondrial membrane 50 homolog (yeast) DLL3 19q13.1-13.3 delta-like 3 (Drosophila) SELV 19q13.2 selenoprotein V FLJ38944 19q13.2 hypothetical protein FLJ38944 MGC20452 LOC390930 19 similar to Charot-Leyden crystal protein; Charcot-Leyden crystal protein; eosinophil lysophospholipase; lysolecithin acylhydrolase; galactin-10 PP13 19q13.1 placental protein 13 LOC390931 19 similar to placental protein 13-like protein LOC148003 19q13.2 similar to placental protein 13; galectin-13 LOC390932 19 similar to Eosinophil lysophospholipase (Charcot-Leyden crystal protein homolog) (Lysolecithin acylhydrolase) (CLC) (Galectin-10) PPL13 19q13.2 placental protein 13-like protein CLC 19q13.1 Charot-Leyden crystal protein LOC342900 19q13.2 hypothetical LOC342900
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1745 34 326 - 2008 17606294
    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
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    Lymphoid/Immunemacrophage
    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
  • 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)
  • 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