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mRNA decay activator protein ZFP36



Rattus norvegicus (Rat)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


Zinc-finger RNA-binding protein that destabilizes numerous cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:27193233). Acts as an 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery. Recruits deadenylase CNOT7 (and probably the CCR4-NOT complex) via association with CNOT1, and hence promotes ARE-mediated mRNA deadenylation. Functions also by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs. Self regulates by destabilizing its own mRNA (By similarity). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:27193233). Binds also to ARE of its own mRNA. Plays a role in anti-inflammatory responses; suppresses tumor necrosis factor (TNF)-alpha production by stimulating ARE-mediated TNF-alpha mRNA decay and several other inflammatory ARE-containing mRNAs in interferon (IFN)- and/or lipopolysaccharide (LPS)-induced macrophages. Plays also a role in the regulation of dendritic cell maturation at the post-transcriptional level, and hence operates as part of a negative feedback loop to limit the inflammatory response. Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia. Positively regulates early adipogenesis of preadipocytes by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA. Plays a role in maintaining skeletal muscle satellite cell quiescence by promoting ARE-mediated mRNA decay of the myogenic determination factor MYOD1 mRNA. Associates also with and regulates the expression of non-ARE-containing target mRNAs at the post-transcriptional level, such as MHC class I mRNAs. Participates in association with argonaute RISC catalytic components in the ARE-mediated mRNA decay mechanism; assists microRNA (miRNA) targeting ARE-containing mRNAs. May also play a role in the regulation of cytoplasmic mRNA decapping; enhances decapping of ARE-containing RNAs, in vitro. Involved in the delivery of target ARE-mRNAs to processing bodies (PBs). In addition to its cytosolic mRNA-decay function, affects nuclear pre-mRNA processing. Negatively regulates nuclear poly(A)-binding protein PABPN1-stimulated polyadenylation activity on ARE-containing pre-mRNA during LPS-stimulated macrophages. Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion. Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis. Plays a role as a tumor suppressor by inhibiting cell proliferation in breast cancer cells (By similarity).By similarity1 Publication


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri96 – 124C3H1-type 1PROSITE-ProRule annotationAdd BLAST29
Zinc fingeri134 – 162C3H1-type 2PROSITE-ProRule annotationAdd BLAST29

GO - Molecular functioni

GO - Biological processi


Molecular functionDevelopmental protein, DNA-binding, Ribonucleoprotein
Biological processmRNA transport, Transport
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
mRNA decay activator protein ZFP36Curated
Alternative name(s):
TPA-induced sequence 11By similarity
TristetraprolinBy similarity
Zinc finger protein 36Imported
Short name:
Zfp-36By similarity
Gene namesi
Synonyms:Tis111 Publication, TtpBy similarity
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620722. Zfp36.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Exosome, Nucleus

Pathology & Biotechi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3L → A: Inhibits nucleus export. 1 Publication1
Mutagenesisi10L → A: Inhibits nucleus export. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000891651 – 320mRNA decay activator protein ZFP36Add BLAST320

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei53Phosphoserine; by MAPKAPK2By similarity1
Modified residuei59PhosphoserineBy similarity1
Modified residuei81PhosphoserineBy similarity1
Modified residuei83PhosphoserineBy similarity1
Modified residuei85PhosphothreonineBy similarity1
Modified residuei86PhosphoserineBy similarity1
Modified residuei179Phosphoserine; by MAPKAPK2By similarity1
Modified residuei190PhosphoserineBy similarity1
Modified residuei211PhosphoserineBy similarity1
Modified residuei221Phosphoserine; by MAPK1; in vitroBy similarity1
Modified residuei251PhosphothreonineBy similarity1
Modified residuei270PhosphoserineBy similarity1
Modified residuei290PhosphoserineBy similarity1
Modified residuei317PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated. Phosphorylation at serine and/or threonine residues occurs in a p38 MAPK- and MAPKAPK2-dependent manner. Phosphorylated by MAPKAPK2 at Ser-53 and Ser-179; phosphorylation increases its stability and cytoplasmic localization, promotes binding to 14-3-3 adapter proteins and inhibits the recruitment of cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase complexes to the mRNA decay machinery, thereby inhibiting ZFP36-induced ARE-containing mRNA deadenylation and decay processes. Phosphorylation by MAPKAPK2 does not impair ARE-containing RNA-binding. Phosphorylated in a MAPKAPK2- and p38 MAPK-dependent manner upon skeletal muscle satellite cell activation; this phosphorylation inhibits ZFP36-mediated mRNA decay activity, and hence stabilizes MYOD1 mRNA. Phosphorylated by MAPK1 upon mitogen stimulation. Phosphorylated at Ser-59 and Ser-86; these phosphorylations increase in a SH3KBP1-dependent manner. Phosphorylated at serine and threonine residues in a pyruvate kinase PKM- and p38 MAPK-dependent manner. Phosphorylation at Ser-53 may participate in the PKM-mediated degradation of ZFP36 in a p38 MAPK-dependent manner. Dephosphorylated by serine/threonine phosphatase 2A at Ser-179.By similarity
Ubiquitinated; pyruvate kinase (PKM)-dependent ubiquitination leads to proteasomal degradation through a p38 MAPK signaling pathway.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases


PTM databases



Subunit structurei

Associates with cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase complexes to trigger ARE-containing mRNA deadenylation and decay processes. Part of a mRNA decay activation complex at least composed of poly(A)-specific exoribonucleases CNOT6, EXOSC2 and XRN1 and mRNA-decapping enzymes DCP1A and DCP2. Associates with the RNA exosome complex. Interacts (via phosphorylated form) with 14-3-3 proteins; these interactions promote exclusion of ZFP36 from cytoplasmic stress granules in response to arsenite treatment in a MAPKAPK2-dependent manner and does not prevent CCR4-NOT deadenylase complex recruitment or ZFP36-induced ARE-containing mRNA deadenylation and decay processes. Interacts with 14-3-3 proteins; these interactions occur in response to rapamycin in an Akt-dependent manner. Interacts with AGO2 and AGO4. Interacts (via C-terminus) with CNOT1; this interaction occurs in a RNA-independent manner and induces mRNA deadenylation. Interacts (via N-terminus) with CNOT6. Interacts with CNOT6L. Interacts (via C-terminus) with CNOT7; this interaction occurs in a RNA-independent manner, induces mRNA deadenylation and is inhibited in a phosphorylation MAPKAPK2-dependent manner. Interacts (via unphosphorylated form) with CNOT8; this interaction occurs in a RNA-independent manner and is inhibited in a phosphorylation MAPKAPK2-dependent manner. Interacts with DCP1A. Interacts (via N-terminus) with DCP2. Interacts with EDC3. Interacts (via N-terminus) with EXOSC2. Interacts with heat shock 70 kDa proteins. Interacts with KHSRP; this interaction increases upon cytokine-induced treatment. Interacts with MAP3K4; this interaction enhances the association with SH3KBP1/CIN85. Interacts with MAPKAPK2; this interaction occurs upon skeletal muscle satellite cell activation. Interacts with NCL. Interacts with NUP214; this interaction increases upon lipopolysaccharide (LPS) stimulation. Interacts with PABPC1; this interaction occurs in a RNA-dependent manner. Interacts (via hypophosphorylated form) with PABPN1 (via RRM domain and C-terminal arginine-rich region); this interaction occurs in the nucleus in a RNA-independent manner, decreases in presence of single-stranded poly(A) RNA-oligomer and in a p38 MAPK-dependent-manner and inhibits nuclear poly(A) tail synthesis. Interacts with PAN2. Interacts (via C3H1-type zinc finger domains) with PKM. Interacts (via C3H1-type zinc finger domains) with nuclear RNA poly(A) polymerase. Interacts with PPP2CA; this interaction occurs in LPS-stimulated cells and induces ZFP36 dephosphorylation, and hence may promote ARE-containing mRNAs decay. Interacts (via C-terminus) with PRR5L (via C-terminus); this interaction may accelerate ZFP36-mediated mRNA decay during stress. Interacts (via C-terminus) with SFN; this interaction occurs in a phosphorylation-dependent manner. Interacts (via extreme C-terminal region) with SH3KBP1/CIN85 (via SH3 domains); this interaction enhances MAP3K4-induced phosphorylation of ZFP36 at Ser-59 and Ser-86 and does not alter neither ZFP36 binding to ARE-containing transcripts nor TNF-alpha mRNA decay. Interacts with XRN1. Interacts (via C-terminus and Ser-179 phosphorylated form) with YWHAB; this interaction occurs in a p38/MAPKAPK2-dependent manner, increases cytoplasmic localization of ZFP36 and protects ZFP36 from Ser-179 dephosphorylation by serine/threonine phosphatase 2A, and hence may be crucial for stabilizing ARE-containing mRNAs. Interacts (via phosphorylated form) with YWHAE. Interacts (via C-terminus) with YWHAG; this interaction occurs in a phosphorylation-dependent manner. Interacts with YWHAH; this interaction occurs in a phosphorylation-dependent manner. Interacts with YWHAQ; this interaction occurs in a phosphorylation-dependent manner. Interacts with (via C-terminus) YWHAZ; this interaction occurs in a phosphorylation-dependent manner. Does not interact with SH3KBP1. Interacts (via P-P-P-P-G repeats) with GIGYF2; the interaction is direct (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases



3D structure databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati64 – 68P-P-P-P-G5
Repeati191 – 195P-P-P-P-G5
Repeati212 – 216P-P-P-P-G5


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 167Necessary for localization of ARE-containing mRNAs to processing bodies (PBs)By similarityAdd BLAST167
Regioni1 – 93Necessary and sufficient for the association with mRNA decay enzymes and mRNA decay activationBy similarityAdd BLAST93
Regioni1 – 15Necessary for nuclear export1 PublicationAdd BLAST15
Regioni88 – 161Necessary for nuclear localization1 PublicationAdd BLAST74
Regioni90 – 166Necessary for RNA-bindingBy similarityAdd BLAST77
Regioni93 – 320Necessary for localization of ARE-containing mRNAs to processing bodies (PBs)By similarityAdd BLAST228
Regioni96 – 187Necessary for interaction with PABPN1By similarityAdd BLAST92
Regioni167 – 320Necessary for mRNA decay activationBy similarityAdd BLAST154
Regioni306 – 320Interaction with CNOT1By similarityAdd BLAST15


The C3H1-type zinc finger domains are necessary for ARE-binding activity.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri96 – 124C3H1-type 1PROSITE-ProRule annotationAdd BLAST29
Zinc fingeri134 – 162C3H1-type 2PROSITE-ProRule annotationAdd BLAST29

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1677. Eukaryota.
COG5063. LUCA.

Family and domain databases

Gene3Di4.10.1000.10. 2 hits.
InterProiView protein in InterPro
IPR000571. Znf_CCCH.
PfamiView protein in Pfam
PF00642. zf-CCCH. 2 hits.
SMARTiView protein in SMART
SM00356. ZnF_C3H1. 2 hits.
SUPFAMiSSF90229. SSF90229. 2 hits.
PROSITEiView protein in PROSITE
PS50103. ZF_C3H1. 2 hits.


Sequence statusi: Complete.

P47973-1 [UniParc]FASTAAdd to basket

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Mass (Da):33,654
Last modified:October 1, 1996 - v1

Sequence databases

Select the link destinations:
Links Updated
X63369 mRNA. Translation: CAA44970.1.
AB025017 Genomic DNA. Translation: BAB12432.1.
BC060308 mRNA. Translation: AAH60308.1.
RefSeqiNP_579824.2. NM_133290.3.

Genome annotation databases

UCSCiRGD:620722. rat.

Similar proteinsi

Entry informationi

Entry nameiTTP_RAT
AccessioniPrimary (citable) accession number: P47973
Secondary accession number(s): Q54AH1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: August 30, 2017
This is version 131 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

Complete proteome, Reference proteome