TTP_MOUSE
ID TTP_MOUSE Reviewed; 319 AA.
AC P22893; P11520;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=mRNA decay activator protein ZFP36 {ECO:0000305};
DE AltName: Full=Growth factor-inducible nuclear protein NUP475 {ECO:0000305};
DE AltName: Full=TPA-induced sequence 11 {ECO:0000303|PubMed:2915901};
DE AltName: Full=Tristetraprolin {ECO:0000303|PubMed:2204625};
DE AltName: Full=Zinc finger protein 36 {ECO:0000303|PubMed:7559666, ECO:0000312|MGI:MGI:99180};
DE Short=Zfp-36 {ECO:0000303|PubMed:7559666};
GN Name=Zfp36 {ECO:0000303|PubMed:7559666, ECO:0000312|MGI:MGI:99180};
GN Synonyms=Nup475 {ECO:0000303|PubMed:1699942},
GN Tis11 {ECO:0000303|PubMed:2915901}, Tis11a,
GN Ttp {ECO:0000303|PubMed:2204625};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=2204625; DOI=10.1016/s0021-9258(17)46259-4;
RA Lai W.S., Stumpo D.J., Blackshear P.J.;
RT "Rapid insulin-stimulated accumulation of an mRNA encoding a proline-rich
RT protein.";
RL J. Biol. Chem. 265:16556-16563(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=1699942; DOI=10.1016/s0021-9258(17)30642-7;
RA Dubois R.N., McLane M.W., Ryder K., Lau L.F., Nathans D.;
RT "A growth factor-inducible nuclear protein with a novel cysteine/histidine
RT repetitive sequence.";
RL J. Biol. Chem. 265:19185-19191(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=SWR/J;
RX PubMed=2915901;
RA Varnum B.C., Lim R.W., Sukhatme V.P., Herschman H.R.;
RT "Nucleotide sequence of a cDNA encoding TIS11, a message induced in Swiss
RT 3T3 cells by the tumor promoter tetradecanoyl phorbol acetate.";
RL Oncogene 4:119-120(1989).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=1861870;
RA Ma Q., Herschman H.R.;
RT "A corrected sequence for the predicted protein from the mitogen-inducible
RT TIS11 primary response gene.";
RL Oncogene 6:1277-1278(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=1996120; DOI=10.1128/mcb.11.3.1754-1758.1991;
RA Varnum B.C., Ma Q., Chi T., Fletcher B.S., Herschman H.R.;
RT "The TIS11 primary response gene is a member of a gene family that encodes
RT proteins with a highly conserved sequence containing an unusual Cys-His
RT repeat.";
RL Mol. Cell. Biol. 11:1754-1758(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=7559666; DOI=10.1074/jbc.270.42.25266;
RA Lai W.S., Thompson M.J., Taylor G.A., Liu Y., Blackshear P.J.;
RT "Promoter analysis of Zfp-36, the mitogen-inducible gene encoding the zinc
RT finger protein tristetraprolin.";
RL J. Biol. Chem. 270:25266-25272(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PHOSPHORYLATION AT SER-220 BY MAPK1.
RX PubMed=7768935; DOI=10.1074/jbc.270.22.13341;
RA Taylor G.A., Thompson M.J., Lai W.S., Blackshear P.J.;
RT "Phosphorylation of tristetraprolin, a potential zinc finger transcription
RT factor, by mitogen stimulation in intact cells and by mitogen-activated
RT protein kinase in vitro.";
RL J. Biol. Chem. 270:13341-13347(1995).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8630730; DOI=10.1016/s1074-7613(00)80411-2;
RA Taylor G.A., Carballo E., Lee D.M., Lai W.S., Thompson M.J., Patel D.D.,
RA Schenkman D.I., Gilkeson G.S., Broxmeyer H.E., Haynes B.F.,
RA Blackshear P.J.;
RT "A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis,
RT and autoimmunity resulting from tristetraprolin (TTP) deficiency.";
RL Immunity 4:445-454(1996).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=9703499; DOI=10.1126/science.281.5379.1001;
RA Carballo E., Lai W.S., Blackshear P.J.;
RT "Feedback inhibition of macrophage tumor necrosis factor-alpha production
RT by tristetraprolin.";
RL Science 281:1001-1005(1998).
RN [11]
RP FUNCTION, RNA-BINDING, AND DISRUPTION PHENOTYPE.
RX PubMed=10330172; DOI=10.1128/mcb.19.6.4311;
RA Lai W.S., Carballo E., Strum J.R., Kennington E.A., Phillips R.S.,
RA Blackshear P.J.;
RT "Evidence that tristetraprolin binds to AU-rich elements and promotes the
RT deadenylation and destabilization of tumor necrosis factor alpha mRNA.";
RL Mol. Cell. Biol. 19:4311-4323(1999).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10706852;
RA Carballo E., Lai W.S., Blackshear P.J.;
RT "Evidence that tristetraprolin is a physiological regulator of granulocyte-
RT macrophage colony-stimulating factor messenger RNA deadenylation and
RT stability.";
RL Blood 95:1891-1899(2000).
RN [13]
RP FUNCTION.
RX PubMed=10805719; DOI=10.1128/mcb.20.11.3753-3763.2000;
RA Stoecklin G., Ming X.F., Looser R., Moroni C.;
RT "Somatic mRNA turnover mutants implicate tristetraprolin in the
RT interleukin-3 mRNA degradation pathway.";
RL Mol. Cell. Biol. 20:3753-3763(2000).
RN [14]
RP FUNCTION, RNA-BINDING, PHOSPHORYLATION, AND INDUCTION.
RX PubMed=11533235; DOI=10.1128/mcb.21.9.6461-6469.2001;
RA Mahtani K.R., Brook M., Dean J.L., Sully G., Saklatvala J., Clark A.R.;
RT "Mitogen-activated protein kinase p38 controls the expression and
RT posttranslational modification of tristetraprolin, a regulator of tumor
RT necrosis factor alpha mRNA stability.";
RL Mol. Cell. Biol. 21:6461-6469(2001).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=11796723; DOI=10.1074/jbc.m111457200;
RA Phillips R.S., Ramos S.B., Blackshear P.J.;
RT "Members of the tristetraprolin family of tandem CCCH zinc finger proteins
RT exhibit CRM1-dependent nucleocytoplasmic shuttling.";
RL J. Biol. Chem. 277:11606-11613(2002).
RN [16]
RP INTERACTION WITH SFN; YWHAB; YWHAG; YWHAH; YWHAQ AND YWHAZ, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF SER-178.
RX PubMed=11886850; DOI=10.1074/jbc.m110465200;
RA Johnson B.A., Stehn J.R., Yaffe M.B., Blackwell T.K.;
RT "Cytoplasmic localization of tristetraprolin involves 14-3-3-dependent and
RT -independent mechanisms.";
RL J. Biol. Chem. 277:18029-18036(2002).
RN [17]
RP FUNCTION, PHOSPHORYLATION AT SER-52 AND SER-178 BY MAPKAPK2, INTERACTION
RP WITH 14-3-3 PROTEINS, SUBCELLULAR LOCATION, RNA-BINDING, AND MUTAGENESIS OF
RP SER-52 AND SER-178.
RX PubMed=15014438; DOI=10.1038/sj.emboj.7600163;
RA Stoecklin G., Stubbs T., Kedersha N., Wax S., Rigby W.F., Blackwell T.K.,
RA Anderson P.;
RT "MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule
RT association and ARE-mRNA decay.";
RL EMBO J. 23:1313-1324(2004).
RN [18]
RP PHOSPHORYLATION AT SER-52 AND SER-178 BY MAPKAPK2; PHOSPHORYLATION AT
RP SER-80; SER-82; SER-85; THR-250 AND SER-316, INTERACTION WITH YWHAB,
RP RNA-BINDING, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14688255; DOI=10.1074/jbc.m310486200;
RA Chrestensen C.A., Schroeder M.J., Shabanowitz J., Hunt D.F., Pelo J.W.,
RA Worthington M.T., Sturgill T.W.;
RT "MAPKAP kinase 2 phosphorylates tristetraprolin on in vivo sites including
RT Ser178, a site required for 14-3-3 binding.";
RL J. Biol. Chem. 279:10176-10184(2004).
RN [19]
RP FUNCTION, RNA-BINDING, AND INDUCTION.
RX PubMed=15187092; DOI=10.1074/jbc.m402059200;
RA Tchen C.R., Brook M., Saklatvala J., Clark A.R.;
RT "The stability of tristetraprolin mRNA is regulated by mitogen-activated
RT protein kinase p38 and by tristetraprolin itself.";
RL J. Biol. Chem. 279:32393-32400(2004).
RN [20]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15967811; DOI=10.1083/jcb.200502088;
RA Kedersha N., Stoecklin G., Ayodele M., Yacono P., Lykke-Andersen J.,
RA Fritzler M.J., Scheuner D., Kaufman R.J., Golan D.E., Anderson P.;
RT "Stress granules and processing bodies are dynamically linked sites of mRNP
RT remodeling.";
RL J. Cell Biol. 169:871-884(2005).
RN [21]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15634918; DOI=10.4049/jimmunol.174.2.953;
RA Ogilvie R.L., Abelson M., Hau H.H., Vlasova I., Blackshear P.J.,
RA Bohjanen P.R.;
RT "Tristetraprolin down-regulates IL-2 gene expression through AU-rich
RT element-mediated mRNA decay.";
RL J. Immunol. 174:953-961(2005).
RN [22]
RP FUNCTION, AND INDUCTION.
RX PubMed=16514065; DOI=10.1182/blood-2005-07-3058;
RA Sauer I., Schaljo B., Vogl C., Gattermeier I., Kolbe T., Mueller M.,
RA Blackshear P.J., Kovarik P.;
RT "Interferons limit inflammatory responses by induction of
RT tristetraprolin.";
RL Blood 107:4790-4797(2006).
RN [23]
RP PHOSPHORYLATION, RNA-BINDING, DISRUPTION PHENOTYPE, MUTAGENESIS OF SER-52
RP AND SER-178, AND INDUCTION.
RX PubMed=16508014; DOI=10.1128/mcb.26.6.2399-2407.2006;
RA Hitti E., Iakovleva T., Brook M., Deppenmeier S., Gruber A.D., Radzioch D.,
RA Clark A.R., Blackshear P.J., Kotlyarov A., Gaestel M.;
RT "Mitogen-activated protein kinase-activated protein kinase 2 regulates
RT tumor necrosis factor mRNA stability and translation mainly by altering
RT tristetraprolin expression, stability, and binding to adenine/uridine-rich
RT element.";
RL Mol. Cell. Biol. 26:2399-2407(2006).
RN [24]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, INDUCTION, AND MUTAGENESIS OF SER-52
RP AND SER-178.
RX PubMed=16508015; DOI=10.1128/mcb.26.6.2408-2418.2006;
RA Brook M., Tchen C.R., Santalucia T., McIlrath J., Arthur J.S.,
RA Saklatvala J., Clark A.R.;
RT "Posttranslational regulation of tristetraprolin subcellular localization
RT and protein stability by p38 mitogen-activated protein kinase and
RT extracellular signal-regulated kinase pathways.";
RL Mol. Cell. Biol. 26:2408-2418(2006).
RN [25]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17030620; DOI=10.1128/mcb.00945-06;
RA Lai W.S., Parker J.S., Grissom S.F., Stumpo D.J., Blackshear P.J.;
RT "Novel mRNA targets for tristetraprolin (TTP) identified by global analysis
RT of stabilized transcripts in TTP-deficient fibroblasts.";
RL Mol. Cell. Biol. 26:9196-9208(2006).
RN [26]
RP FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=17288565; DOI=10.1111/j.1742-4658.2007.05632.x;
RA Lin N.Y., Lin C.T., Chen Y.L., Chang C.J.;
RT "Regulation of tristetraprolin during differentiation of 3T3-L1
RT preadipocytes.";
RL FEBS J. 274:867-878(2007).
RN [27]
RP INTERACTION WITH PPP2CA AND YWHAB, PHOSPHORYLATION AT SER-178 BY MAPKAPK2,
RP DEPHOSPHORYLATION AT SER-178 BY SERINE/THREONINE PHOSPHATASE 2A, AND
RP MUTAGENESIS OF SER-52 AND SER-178.
RX PubMed=17170118; DOI=10.1074/jbc.m607347200;
RA Sun L., Stoecklin G., Van Way S., Hinkovska-Galcheva V., Guo R.F.,
RA Anderson P., Shanley T.P.;
RT "Tristetraprolin (TTP)-14-3-3 complex formation protects TTP from
RT dephosphorylation by protein phosphatase 2a and stabilizes tumor necrosis
RT factor-alpha mRNA.";
RL J. Biol. Chem. 282:3766-3777(2007).
RN [28]
RP RNA-BINDING.
RX PubMed=17971298; DOI=10.1016/j.bbrc.2007.10.119;
RA Lin N.Y., Lin C.T., Chang C.J.;
RT "Modulation of immediate early gene expression by tristetraprolin in the
RT differentiation of 3T3-L1 cells.";
RL Biochem. Biophys. Res. Commun. 365:69-74(2008).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [30]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19188452; DOI=10.1128/mcb.00982-08;
RA Horner T.J., Lai W.S., Stumpo D.J., Blackshear P.J.;
RT "Stimulation of polo-like kinase 3 mRNA decay by tristetraprolin.";
RL Mol. Cell. Biol. 29:1999-2010(2009).
RN [31]
RP INDUCTION.
RX PubMed=20166898; DOI=10.3109/08977190903578660;
RA Hacker C., Valchanova R., Adams S., Munz B.;
RT "ZFP36L1 is regulated by growth factors and cytokines in keratinocytes and
RT influences their VEGF production.";
RL Growth Factors 28:178-190(2010).
RN [32]
RP FUNCTION, PHOSPHORYLATION AT SER-52 AND SER-178 BY MAPKAPK2, RNA-BINDING,
RP INTERACTION WITH 14-3-3 PROTEINS; CNOT7; CNOT8 AND PABPC1, ASSOCIATION WITH
RP THE CCR4-NOT DEADENYLASE COMPLEX, AND MUTAGENESIS OF SER-52 AND SER-178.
RX PubMed=20595389; DOI=10.1074/jbc.m110.136473;
RA Marchese F.P., Aubareda A., Tudor C., Saklatvala J., Clark A.R., Dean J.L.;
RT "MAPKAP kinase 2 blocks tristetraprolin-directed mRNA decay by inhibiting
RT CAF1 deadenylase recruitment.";
RL J. Biol. Chem. 285:27590-27600(2010).
RN [33]
RP MUTAGENESIS OF PRO-303, AND LACK OF INTERACTION WITH SH3KBP1.
RX PubMed=20221403; DOI=10.1371/journal.pone.0009588;
RA Kedar V.P., Darby M.K., Williams J.G., Blackshear P.J.;
RT "Phosphorylation of human tristetraprolin in response to its interaction
RT with the Cbl interacting protein CIN85.";
RL PLoS ONE 5:E9588-E9588(2010).
RN [34]
RP FUNCTION, RNA-BINDING, PHOSPHORYLATION BY MAPKAPK2, INTERACTION WITH
RP CNOT6L; PABPC1; PAN2 AND YWHAE, ASSOCIATION WITH THE CCR4-NOT AND PAN2-PAN3
RP DEADENYLASE COMPLEXES, AND MUTAGENESIS OF SER-52 AND SER-178.
RX PubMed=21078877; DOI=10.1128/mcb.00717-10;
RA Clement S.L., Scheckel C., Stoecklin G., Lykke-Andersen J.;
RT "Phosphorylation of tristetraprolin by MK2 impairs AU-rich element mRNA
RT decay by preventing deadenylase recruitment.";
RL Mol. Cell. Biol. 31:256-266(2011).
RN [35]
RP FUNCTION, RNA-BINDING, AND INTERACTION WITH CNOT1 AND CNOT7.
RX PubMed=21278420; DOI=10.1093/nar/gkr011;
RA Sandler H., Kreth J., Timmers H.T., Stoecklin G.;
RT "Not1 mediates recruitment of the deadenylase Caf1 to mRNAs targeted for
RT degradation by tristetraprolin.";
RL Nucleic Acids Res. 39:4373-4386(2011).
RN [36]
RP FUNCTION, RNA-BINDING, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=22701344; DOI=10.7150/ijbs.4036;
RA Lin N.Y., Lin T.Y., Yang W.H., Wang S.C., Wang K.T., Su Y.L., Jiang Y.W.,
RA Chang G.D., Chang C.J.;
RT "Differential expression and functional analysis of the tristetraprolin
RT family during early differentiation of 3T3-L1 preadipocytes.";
RL Int. J. Biol. Sci. 8:761-777(2012).
RN [37]
RP FUNCTION, INTERACTION WITH PABPN1 AND RNA POLY(A) POLYMERASE, AND
RP SUBCELLULAR LOCATION.
RX PubMed=22844456; DOI=10.1371/journal.pone.0041313;
RA Su Y.L., Wang S.C., Chi ang P.Y., Lin N.Y., Shen Y.F., Chang G.D.,
RA Chang C.J.;
RT "Tristetraprolin inhibits poly(A)-tail synthesis in nuclear mRNA that
RT contains AU-rich elements by interacting with poly(A)-binding protein
RT nuclear 1.";
RL PLoS ONE 7:E41313-E41313(2012).
RN [38]
RP INDUCTION.
RX PubMed=23046558; DOI=10.1186/2044-5040-2-21;
RA Farina N.H., Hausburg M., Betta N.D., Pulliam C., Srivastava D.,
RA Cornelison D., Olwin B.B.;
RT "A role for RNA post-transcriptional regulation in satellite cell
RT activation.";
RL Skelet. Muscle 2:21-21(2012).
RN [39]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=24733888; DOI=10.1073/pnas.1320873111;
RA Tan F.E., Elowitz M.B.;
RT "Brf1 posttranscriptionally regulates pluripotency and differentiation
RT responses downstream of Erk MAP kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:1740-1748(2014).
RN [40]
RP INTERACTION WITH MAPKAPK2, PHOSPHORYLATION, TISSUE SPECIFICITY, INDUCTION,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=25815583; DOI=10.7554/elife.03390;
RA Hausburg M.A., Doles J.D., Clement S.L., Cadwallader A.B., Hall M.N.,
RA Blackshear P.J., Lykke-Andersen J., Olwin B.B.;
RT "Post-transcriptional regulation of satellite cell quiescence by TTP-
RT mediated mRNA decay.";
RL Elife 4:E03390-E03390(2015).
RN [41]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=27193233; DOI=10.1007/s00726-016-2261-9;
RA Nowotarski S.L., Origanti S., Sass-Kuhn S., Shantz L.M.;
RT "Destabilization of the ornithine decarboxylase mRNA transcript by the RNA-
RT binding protein tristetraprolin.";
RL Amino Acids 48:2303-2311(2016).
RN [42]
RP INTERACTION WITH GIGYF2, AND MUTAGENESIS OF 64-PRO--PRO-66;
RP 191-PRO--PRO-193 AND 212-PRO--PRO-214.
RX PubMed=26763119; DOI=10.1261/rna.054833.115;
RA Fu R., Olsen M.T., Webb K., Bennett E.J., Lykke-Andersen J.;
RT "Recruitment of the 4EHP-GYF2 cap-binding complex to tetraproline motifs of
RT tristetraprolin promotes repression and degradation of mRNAs with AU-rich
RT elements.";
RL RNA 22:373-382(2016).
RN [43]
RP STRUCTURE BY NMR OF 91-163 IN COMPLEX WITH ZINC.
RX PubMed=12515557; DOI=10.1021/bi026988m;
RA Amann B.T., Worthington M.T., Berg J.M.;
RT "A Cys3His zinc-binding domain from Nup475/tristetraprolin: a novel fold
RT with a disklike structure.";
RL Biochemistry 42:217-221(2003).
CC -!- FUNCTION: Zinc-finger RNA-binding protein that destabilizes numerous
CC cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by
CC promoting their poly(A) tail removal or deadenylation, and hence
CC provide a mechanism for attenuating protein synthesis (PubMed:10330172,
CC PubMed:10706852, PubMed:10805719, PubMed:15014438, PubMed:15187092,
CC PubMed:15634918, PubMed:17030620, PubMed:19188452, PubMed:20595389,
CC PubMed:21078877, PubMed:22701344, PubMed:27193233). Acts as an 3'-
CC untranslated region (UTR) ARE mRNA-binding adapter protein to
CC communicate signaling events to the mRNA decay machinery
CC (PubMed:21278420). Recruits deadenylase CNOT7 (and probably the CCR4-
CC NOT complex) via association with CNOT1, and hence promotes ARE-
CC mediated mRNA deadenylation (PubMed:21278420). Functions also by
CC recruiting components of the cytoplasmic RNA decay machinery to the
CC bound ARE-containing mRNAs (PubMed:21278420). Self regulates by
CC destabilizing its own mRNA (PubMed:15187092, PubMed:17288565). Binds to
CC 3'-UTR ARE of numerous mRNAs and of its own mRNA (PubMed:11533235,
CC PubMed:15187092, PubMed:16508014, PubMed:17288565, PubMed:17971298,
CC PubMed:20595389, PubMed:21078877, PubMed:21278420, PubMed:22701344,
CC PubMed:27193233). Plays a role in anti-inflammatory responses;
CC suppresses tumor necrosis factor (TNF)-alpha production by stimulating
CC ARE-mediated TNF-alpha mRNA decay and several other inflammatory ARE-
CC containing mRNAs in interferon (IFN)- and/or lipopolysaccharide (LPS)-
CC induced macrophages (PubMed:8630730, PubMed:9703499, PubMed:15014438,
CC PubMed:16514065). Also plays a role in the regulation of dendritic cell
CC maturation at the post-transcriptional level, and hence operates as
CC part of a negative feedback loop to limit the inflammatory response (By
CC similarity). Promotes ARE-mediated mRNA decay of hypoxia-inducible
CC factor HIF1A mRNA during the response of endothelial cells to hypoxia
CC (By similarity). Positively regulates early adipogenesis of
CC preadipocytes by promoting ARE-mediated mRNA decay of immediate early
CC genes (IEGs) (PubMed:22701344). Negatively regulates
CC hematopoietic/erythroid cell differentiation by promoting ARE-mediated
CC mRNA decay of the transcription factor STAT5B mRNA (By similarity).
CC Plays a role in maintaining skeletal muscle satellite cell quiescence
CC by promoting ARE-mediated mRNA decay of the myogenic determination
CC factor MYOD1 mRNA (PubMed:25815583). Associates also with and regulates
CC the expression of non-ARE-containing target mRNAs at the post-
CC transcriptional level, such as MHC class I mRNAs (By similarity).
CC Participates in association with argonaute RISC catalytic components in
CC the ARE-mediated mRNA decay mechanism; assists microRNA (miRNA)
CC targeting ARE-containing mRNAs (By similarity). May also play a role in
CC the regulation of cytoplasmic mRNA decapping; enhances decapping of
CC ARE-containing RNAs, in vitro (By similarity). Involved in the delivery
CC of target ARE-mRNAs to processing bodies (PBs) (By similarity). In
CC addition to its cytosolic mRNA-decay function, affects nuclear pre-mRNA
CC processing (PubMed:22844456). Negatively regulates nuclear poly(A)-
CC binding protein PABPN1-stimulated polyadenylation activity on ARE-
CC containing pre-mRNA during LPS-stimulated macrophages
CC (PubMed:22844456). Also involved in the regulation of stress granule
CC (SG) and P-body (PB) formation and fusion (PubMed:15967811). Plays a
CC role in the regulation of keratinocyte proliferation, differentiation
CC and apoptosis (By similarity). Plays a role as a tumor suppressor by
CC inhibiting cell proliferation in breast cancer cells (By similarity).
CC {ECO:0000250|UniProtKB:P26651, ECO:0000269|PubMed:10330172,
CC ECO:0000269|PubMed:10706852, ECO:0000269|PubMed:10805719,
CC ECO:0000269|PubMed:11533235, ECO:0000269|PubMed:15014438,
CC ECO:0000269|PubMed:15187092, ECO:0000269|PubMed:15634918,
CC ECO:0000269|PubMed:15967811, ECO:0000269|PubMed:16508014,
CC ECO:0000269|PubMed:16514065, ECO:0000269|PubMed:17030620,
CC ECO:0000269|PubMed:17288565, ECO:0000269|PubMed:17971298,
CC ECO:0000269|PubMed:19188452, ECO:0000269|PubMed:20595389,
CC ECO:0000269|PubMed:21078877, ECO:0000269|PubMed:21278420,
CC ECO:0000269|PubMed:22701344, ECO:0000269|PubMed:22844456,
CC ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:27193233,
CC ECO:0000269|PubMed:8630730, ECO:0000269|PubMed:9703499}.
CC -!- SUBUNIT: Associates with cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase
CC complexes to trigger ARE-containing mRNA deadenylation and decay
CC processes (PubMed:20595389, PubMed:21078877). Part of a mRNA decay
CC activation complex at least composed of poly(A)-specific
CC exoribonucleases CNOT6, EXOSC2 and XRN1 and mRNA-decapping enzymes
CC DCP1A and DCP2 (By similarity). Associates with the RNA exosome complex
CC (By similarity). Interacts (via phosphorylated form) with 14-3-3
CC proteins; these interactions promote exclusion of ZFP36 from
CC cytoplasmic stress granules in response to arsenite treatment in a
CC MAPKAPK2-dependent manner and does not prevent CCR4-NOT deadenylase
CC complex recruitment or ZFP36-induced ARE-containing mRNA deadenylation
CC and decay processes (PubMed:15014438, PubMed:20595389). Interacts with
CC 14-3-3 proteins; these interactions occur in response to rapamycin in
CC an Akt-dependent manner (By similarity). Interacts with AGO2 and AGO4
CC (By similarity). Interacts (via C-terminus) with CNOT1; this
CC interaction occurs in a RNA-independent manner and induces mRNA
CC deadenylation (PubMed:21278420). Interacts (via N-terminus) with CNOT6
CC (By similarity). Interacts with CNOT6L (PubMed:21078877). Interacts
CC (via C-terminus) with CNOT7; this interaction occurs in a RNA-
CC independent manner, induces mRNA deadenylation and is inhibited in a
CC phosphorylation MAPKAPK2-dependent manner (PubMed:20595389,
CC PubMed:21278420). Interacts (via unphosphorylated form) with CNOT8;
CC this interaction occurs in a RNA-independent manner and is inhibited in
CC a phosphorylation MAPKAPK2-dependent manner (PubMed:20595389).
CC Interacts with DCP1A (By similarity). Interacts (via N-terminus) with
CC DCP2 (By similarity). Interacts with EDC3 (By similarity). Interacts
CC (via N-terminus) with EXOSC2 (By similarity). Interacts with heat shock
CC 70 kDa proteins (By similarity). Interacts with KHSRP; this interaction
CC increases upon cytokine-induced treatment (By similarity). Interacts
CC with MAP3K4; this interaction enhances the association with
CC SH3KBP1/CIN85 (By similarity). Interacts with MAPKAPK2; this
CC interaction occurs upon skeletal muscle satellite cell activation
CC (PubMed:25815583). Interacts with NCL (By similarity). Interacts with
CC NUP214; this interaction increases upon lipopolysaccharide (LPS)
CC stimulation (By similarity). Interacts with PABPC1; this interaction
CC occurs in a RNA-dependent manner (PubMed:20595389, PubMed:21078877).
CC Interacts (via hypophosphorylated form) with PABPN1 (via RRM domain and
CC C-terminal arginine-rich region); this interaction occurs in the
CC nucleus in a RNA-independent manner, decreases in presence of single-
CC stranded poly(A) RNA-oligomer and in a p38 MAPK-dependent-manner and
CC inhibits nuclear poly(A) tail synthesis (PubMed:22844456). Interacts
CC with PAN2 (PubMed:21078877). Interacts (via C3H1-type zinc finger
CC domains) with PKM (By similarity). Interacts (via C3H1-type zinc finger
CC domains) with nuclear RNA poly(A) polymerase (PubMed:22844456).
CC Interacts with PPP2CA; this interaction occurs in LPS-stimulated cells
CC and induces ZFP36 dephosphorylation, and hence may promote ARE-
CC containing mRNAs decay (PubMed:17170118). Interacts (via C-terminus)
CC with PRR5L (via C-terminus); this interaction may accelerate ZFP36-
CC mediated mRNA decay during stress (By similarity). Interacts (via C-
CC terminus) with SFN; this interaction occurs in a phosphorylation-
CC dependent manner (PubMed:11886850). Interacts (via extreme C-terminal
CC region) with SH3KBP1/CIN85 (via SH3 domains); this interaction enhances
CC MAP3K4-induced phosphorylation of ZFP36 at Ser-58 and Ser-85 and does
CC not alter neither ZFP36 binding to ARE-containing transcripts nor TNF-
CC alpha mRNA decay (By similarity). Interacts with XRN1 (By similarity).
CC Interacts (via C-terminus and Ser-178 phosphorylated form) with YWHAB;
CC this interaction occurs in a p38/MAPKAPK2-dependent manner, increases
CC cytoplasmic localization of ZFP36 and protects ZFP36 from Ser-178
CC dephosphorylation by serine/threonine phosphatase 2A, and hence may be
CC crucial for stabilizing ARE-containing mRNAs (PubMed:14688255,
CC PubMed:17170118). Interacts (via phosphorylated form) with YWHAE
CC (PubMed:21078877). Interacts (via C-terminus) with YWHAG; this
CC interaction occurs in a phosphorylation-dependent manner
CC (PubMed:11886850). Interacts with YWHAH; this interaction occurs in a
CC phosphorylation-dependent manner (PubMed:11886850). Interacts with
CC YWHAQ; this interaction occurs in a phosphorylation-dependent manner
CC (PubMed:11886850). Interacts with (via C-terminus) YWHAZ; this
CC interaction occurs in a phosphorylation-dependent manner
CC (PubMed:11886850). Does not interact with SH3KBP1 (PubMed:20221403).
CC Interacts (via the 4EHP-binding motif) with EIF4E2; the interaction is
CC direct (By similarity). Interacts (via P-P-P-P-G repeats) with GIGYF2;
CC the interaction is direct (PubMed:26763119).
CC {ECO:0000250|UniProtKB:P26651, ECO:0000269|PubMed:11886850,
CC ECO:0000269|PubMed:14688255, ECO:0000269|PubMed:15014438,
CC ECO:0000269|PubMed:17170118, ECO:0000269|PubMed:20221403,
CC ECO:0000269|PubMed:20595389, ECO:0000269|PubMed:21078877,
CC ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:22844456,
CC ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:26763119}.
CC -!- INTERACTION:
CC P22893; A5YKK6: CNOT1; Xeno; NbExp=5; IntAct=EBI-647803, EBI-1222758;
CC P22893; Q9UIV1: CNOT7; Xeno; NbExp=3; IntAct=EBI-647803, EBI-2105113;
CC P22893; P31946: YWHAB; Xeno; NbExp=5; IntAct=EBI-647803, EBI-359815;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11796723,
CC ECO:0000269|PubMed:11886850, ECO:0000269|PubMed:15014438,
CC ECO:0000269|PubMed:16508015, ECO:0000269|PubMed:22844456}. Cytoplasm
CC {ECO:0000269|PubMed:11796723, ECO:0000269|PubMed:11886850,
CC ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:16508015,
CC ECO:0000269|PubMed:17288565, ECO:0000269|PubMed:22844456,
CC ECO:0000269|PubMed:24733888, ECO:0000269|PubMed:9703499}. Cytoplasmic
CC granule {ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15967811}.
CC Cytoplasm, P-body {ECO:0000269|PubMed:15967811}. Note=Shuttles between
CC nucleus and cytoplasm in a CRM1-dependent manner (PubMed:11796723,
CC PubMed:11886850). Localized predominantly in the cytoplasm in a p38
CC MAPK- and YWHAB-dependent manner (PubMed:11886850, PubMed:16508015).
CC Colocalizes with SH3KBP1 and MAP3K4 in the cytoplasm (By similarity).
CC Component of cytoplasmic stress granules (SGs) (PubMed:15967811).
CC Localizes to cytoplasmic stress granules upon energy starvation
CC (PubMed:15014438). Localizes in processing bodies (PBs) (By
CC similarity). Excluded from stress granules in a phosphorylation
CC MAPKAPK2-dependent manner (PubMed:15014438). Shuttles in and out of
CC both cytoplasmic P-body and SGs (PubMed:15967811).
CC {ECO:0000250|UniProtKB:P26651, ECO:0000269|PubMed:11796723,
CC ECO:0000269|PubMed:11886850, ECO:0000269|PubMed:15014438,
CC ECO:0000269|PubMed:15967811, ECO:0000269|PubMed:16508015}.
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle satellite cells
CC (PubMed:25815583). Strongly expressed in differentiated adipocytes
CC compared to preadipocytes (at protein level) (PubMed:22701344).
CC Expressed in embryonic stem cells (ESCs) (PubMed:24733888). Expressed
CC in heart, placenta, kidney, intestine, liver, lung, thymus, fat and
CC spleen (PubMed:2204625, PubMed:1699942). {ECO:0000269|PubMed:1699942,
CC ECO:0000269|PubMed:2204625, ECO:0000269|PubMed:22701344,
CC ECO:0000269|PubMed:24733888, ECO:0000269|PubMed:25815583}.
CC -!- INDUCTION: Up-regulated during adipocyte differentiation
CC (PubMed:17288565, PubMed:22701344). Up-regulated transiently in
CC response to fibroblast growth factor FGF4 in a MAPK-dependent manner in
CC embryonic stem cells (ESCs) (PubMed:24733888). Up-regulated by
CC interferons and/or lipopolysaccharide (LPS) in a STAT1- and p38 MAPK-
CC dependent manner (PubMed:11533235, PubMed:16514065, PubMed:16508014,
CC PubMed:16508015). Down-regulated in muscle satellite cells upon muscle
CC injury (at protein level) (PubMed:25815583). Up-regulated by various
CC mitogens (PubMed:7559666). Up-regulated by LPS and TNF-alpha
CC (PubMed:9703499). Up-regulated by interferon IFN-gamma and/or LPS in a
CC STAT1- and p38 MAPK-dependent manner (PubMed:15187092,
CC PubMed:16514065). Up-regulated during adipocyte differentiation
CC (PubMed:22701344). Up-regulated in keratinocytes during epidermal
CC repair after wound healing (PubMed:20166898). Down-regulated during the
CC conversion from quiescence to activated satellite cells upon muscle
CC injury (PubMed:23046558, PubMed:25815583).
CC {ECO:0000269|PubMed:11533235, ECO:0000269|PubMed:15187092,
CC ECO:0000269|PubMed:16508014, ECO:0000269|PubMed:16508015,
CC ECO:0000269|PubMed:16514065, ECO:0000269|PubMed:17288565,
CC ECO:0000269|PubMed:20166898, ECO:0000269|PubMed:22701344,
CC ECO:0000269|PubMed:23046558, ECO:0000269|PubMed:24733888,
CC ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:7559666,
CC ECO:0000269|PubMed:9703499}.
CC -!- DOMAIN: The C3H1-type zinc finger domains are necessary for ARE-binding
CC activity. {ECO:0000250|UniProtKB:P26651}.
CC -!- PTM: Phosphorylated (PubMed:11533235). Phosphorylation at serine and/or
CC threonine residues occurs in a p38 MAPK- and MAPKAPK2-dependent manner
CC (PubMed:11533235). Phosphorylated by MAPKAPK2 at Ser-52 and Ser-178;
CC phosphorylation increases its stability and cytoplasmic localization,
CC promotes binding to 14-3-3 adapter proteins and inhibits the
CC recruitment of cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase complexes
CC to the mRNA decay machinery, thereby inhibiting ZFP36-induced ARE-
CC containing mRNA deadenylation and decay processes (PubMed:15014438,
CC PubMed:14688255, PubMed:16508014, PubMed:16508015, PubMed:17170118,
CC PubMed:20595389, PubMed:21078877). Phosphorylation by MAPKAPK2 does not
CC impair ARE-containing RNA-binding (PubMed:20595389, PubMed:21078877).
CC Phosphorylated in a MAPKAPK2- and p38 MAPK-dependent manner upon
CC skeletal muscle satellite cell activation; this phosphorylation
CC inhibits ZFP36-mediated mRNA decay activity, and hence stabilizes MYOD1
CC mRNA (PubMed:25815583). Phosphorylated by MAPK1 upon mitogen
CC stimulation (PubMed:7768935, PubMed:14688255). Phosphorylated at Ser-58
CC and Ser-85; these phosphorylations increase in a SH3KBP1-dependent
CC manner (By similarity). Phosphorylated at serine and threonine residues
CC in a pyruvate kinase PKM- and p38 MAPK-dependent manner (By
CC similarity). Phosphorylation at Ser-52 may participate in the PKM-
CC mediated degradation of ZFP36 in a p38 MAPK-dependent manner (By
CC similarity). Dephosphorylated by serine/threonine phosphatase 2A at
CC Ser-178 (PubMed:11533235, PubMed:17170118).
CC {ECO:0000250|UniProtKB:P26651, ECO:0000269|PubMed:11533235,
CC ECO:0000269|PubMed:14688255, ECO:0000269|PubMed:15014438,
CC ECO:0000269|PubMed:16508014, ECO:0000269|PubMed:16508015,
CC ECO:0000269|PubMed:17170118, ECO:0000269|PubMed:20595389,
CC ECO:0000269|PubMed:21078877, ECO:0000269|PubMed:25815583,
CC ECO:0000269|PubMed:7768935}.
CC -!- PTM: Ubiquitinated; pyruvate kinase (PKM)-dependent ubiquitination
CC leads to proteasomal degradation through a p38 MAPK signaling pathway.
CC {ECO:0000250|UniProtKB:P26651}.
CC -!- DISRUPTION PHENOTYPE: Mice appear normal at birth, but within 1-8 weeks
CC after birth they develop a complex syndrome of cachexia, arthritis,
CC autoimmunity, myeloid hyperplasia and general inflammation
CC (PubMed:8630730). Show precocious skeletal muscle satellite cell
CC activation and increased satellite cell fusion into myofibers
CC (PubMed:25815583). Show higher levels of tumor necrosis factor (TNF)-
CC alpha mRNA and protein in macrophages and an excess of circulating TNF-
CC alpha (PubMed:8630730, PubMed:9703499, PubMed:16508014). Show higher
CC levels of granulocyte-macrophage colony-stimulating factor (GM-CSF)
CC expression in macrophages and an excess of GM-CSF secretion upon
CC lipopolysaccharide (LPS) stimulation (PubMed:10706852). Show higher
CC levels of serine/threonine-protein kinase PLK3 expression in
CC macrophages (PubMed:19188452). Show higher levels of interleukin IL2
CC expression in splenocytes and T lymphocytes and an excess of IL2
CC secretion upon T cell activation (PubMed:15634918). Show an increase in
CC the stability of numerous mRNAs, such as TNF-alpha, GM-CSF, IL2 and
CC PLK3 mRNAs (PubMed:9703499, PubMed:10706852, PubMed:15634918,
CC PubMed:17030620, PubMed:19188452). Show an absence of ARE-containing
CC transcript deadenylation (PubMed:10330172). Mice with a double knockout
CC of ZFP36 and MAPKAPK2 show increased amounts of TNF in macrophages
CC almost comparable to single ZFP36 knockout (PubMed:16508014).
CC {ECO:0000269|PubMed:10330172, ECO:0000269|PubMed:10706852,
CC ECO:0000269|PubMed:15634918, ECO:0000269|PubMed:16508014,
CC ECO:0000269|PubMed:17030620, ECO:0000269|PubMed:19188452,
CC ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:8630730,
CC ECO:0000269|PubMed:9703499}.
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DR EMBL; M57422; AAA40498.1; -; mRNA.
DR EMBL; M58691; AAA39837.1; -; mRNA.
DR EMBL; X14678; CAA32807.1; ALT_SEQ; mRNA.
DR EMBL; M58565; AAA72947.1; -; mRNA.
DR EMBL; L42317; AAC37676.1; -; Genomic_DNA.
DR EMBL; BC021391; AAH21391.1; -; mRNA.
DR CCDS; CCDS21041.1; -.
DR PIR; A36600; A36600.
DR PIR; S04743; S04743.
DR RefSeq; NP_035886.1; NM_011756.4.
DR PDB; 1M9O; NMR; -; A=91-163.
DR PDBsum; 1M9O; -.
DR AlphaFoldDB; P22893; -.
DR SMR; P22893; -.
DR BioGRID; 204658; 7.
DR IntAct; P22893; 34.
DR MINT; P22893; -.
DR STRING; 10090.ENSMUSP00000057815; -.
DR iPTMnet; P22893; -.
DR PhosphoSitePlus; P22893; -.
DR jPOST; P22893; -.
DR PaxDb; P22893; -.
DR PeptideAtlas; P22893; -.
DR PRIDE; P22893; -.
DR ProteomicsDB; 300052; -.
DR Antibodypedia; 1121; 382 antibodies from 26 providers.
DR DNASU; 22695; -.
DR Ensembl; ENSMUST00000051241; ENSMUSP00000057815; ENSMUSG00000044786.
DR GeneID; 22695; -.
DR KEGG; mmu:22695; -.
DR UCSC; uc009fys.1; mouse.
DR CTD; 7538; -.
DR MGI; MGI:99180; Zfp36.
DR VEuPathDB; HostDB:ENSMUSG00000044786; -.
DR eggNOG; KOG1677; Eukaryota.
DR GeneTree; ENSGT00940000162360; -.
DR HOGENOM; CLU_033040_2_0_1; -.
DR InParanoid; P22893; -.
DR OMA; WGLARSP; -.
DR OrthoDB; 1541140at2759; -.
DR PhylomeDB; P22893; -.
DR TreeFam; TF315463; -.
DR Reactome; R-MMU-450513; Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA.
DR BioGRID-ORCS; 22695; 5 hits in 76 CRISPR screens.
DR ChiTaRS; Zfp36; mouse.
DR EvolutionaryTrace; P22893; -.
DR PRO; PR:P22893; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P22893; protein.
DR Bgee; ENSMUSG00000044786; Expressed in granulocyte and 211 other tissues.
DR ExpressionAtlas; P22893; baseline and differential.
DR Genevisible; P22893; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0070578; C:RISC-loading complex; ISO:MGI.
DR GO; GO:0071889; F:14-3-3 protein binding; IDA:UniProtKB.
DR GO; GO:0019957; F:C-C chemokine binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; IDA:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISO:MGI.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0070063; F:RNA polymerase binding; IDA:UniProtKB.
DR GO; GO:0061158; P:3'-UTR-mediated mRNA destabilization; IDA:UniProtKB.
DR GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; ISS:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; ISS:UniProtKB.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR GO; GO:0000165; P:MAPK cascade; IDA:UniProtKB.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; IDA:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; ISS:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; ISS:UniProtKB.
DR GO; GO:0030099; P:myeloid cell differentiation; IMP:MGI.
DR GO; GO:0045647; P:negative regulation of erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:1902037; P:negative regulation of hematopoietic stem cell differentiation; IMP:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IMP:UniProtKB.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IMP:MGI.
DR GO; GO:1904246; P:negative regulation of polynucleotide adenylyltransferase activity; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0032897; P:negative regulation of viral transcription; ISS:UniProtKB.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IDA:MGI.
DR GO; GO:0031086; P:nuclear-transcribed mRNA catabolic process, deadenylation-independent decay; ISS:UniProtKB.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IDA:MGI.
DR GO; GO:0038066; P:p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:1901835; P:positive regulation of deadenylation-independent decapping of nuclear-transcribed mRNA; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IDA:UniProtKB.
DR GO; GO:1904582; P:positive regulation of intracellular mRNA localization; ISS:UniProtKB.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; ISS:UniProtKB.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IMP:UniProtKB.
DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IDA:UniProtKB.
DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; IDA:UniProtKB.
DR GO; GO:1902172; P:regulation of keratinocyte apoptotic process; ISS:UniProtKB.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; ISS:UniProtKB.
DR GO; GO:0010837; P:regulation of keratinocyte proliferation; ISS:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0042594; P:response to starvation; ISS:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IDA:UniProtKB.
DR GO; GO:0050779; P:RNA destabilization; IMP:MGI.
DR IDEAL; IID50272; -.
DR InterPro; IPR045877; ZFP36-like.
DR InterPro; IPR000571; Znf_CCCH.
DR InterPro; IPR036855; Znf_CCCH_sf.
DR PANTHER; PTHR12547; PTHR12547; 1.
DR Pfam; PF00642; zf-CCCH; 2.
DR SMART; SM00356; ZnF_C3H1; 2.
DR SUPFAM; SSF90229; SSF90229; 2.
DR PROSITE; PS50103; ZF_C3H1; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Developmental protein; DNA-binding; Exosome;
KW Metal-binding; mRNA transport; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Ribonucleoprotein; Transport; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..319
FT /note="mRNA decay activator protein ZFP36"
FT /id="PRO_0000089164"
FT REPEAT 63..67
FT /note="P-P-P-P-G"
FT REPEAT 190..194
FT /note="P-P-P-P-G"
FT REPEAT 211..215
FT /note="P-P-P-P-G"
FT ZN_FING 95..123
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 133..161
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 1..166
FT /note="Necessary for localization of ARE-containing mRNAs
FT to processing bodies (PBs)"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT REGION 1..92
FT /note="Necessary and sufficient for the association with
FT mRNA decay enzymes and mRNA decay activation"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT REGION 1..15
FT /note="Necessary for nuclear export"
FT /evidence="ECO:0000250|UniProtKB:P47973"
FT REGION 65..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..160
FT /note="Necessary for nuclear localization"
FT /evidence="ECO:0000250|UniProtKB:P47973"
FT REGION 89..165
FT /note="Necessary for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT REGION 92..319
FT /note="Necessary for localization of ARE-containing mRNAs
FT to processing bodies (PBs)"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT REGION 95..186
FT /note="Necessary for interaction with PABPN1"
FT /evidence="ECO:0000269|PubMed:22844456"
FT REGION 166..319
FT /note="Necessary for mRNA decay activation"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT REGION 179..309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..319
FT /note="Interaction with CNOT1"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT COMPBIAS 65..84
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..287
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 52
FT /note="Phosphoserine; by MAPKAPK2"
FT /evidence="ECO:0000269|PubMed:14688255,
FT ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:20595389"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14688255"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14688255"
FT MOD_RES 84
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14688255"
FT MOD_RES 178
FT /note="Phosphoserine; by MAPKAPK2"
FT /evidence="ECO:0000269|PubMed:14688255,
FT ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:20595389"
FT MOD_RES 189
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT MOD_RES 220
FT /note="Phosphoserine; by MAPK1; in vitro"
FT /evidence="ECO:0000269|PubMed:7768935"
FT MOD_RES 250
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:14688255"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT MOD_RES 289
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26651"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14688255"
FT MUTAGEN 52
FT /note="S->A: Impairs phosphorylation by MAPKAPK2, decreases
FT its stability and cytoplasmic localization, increases
FT interaction with PPP2CA, inhibits binding to 14-3-3
FT proteins, but does not impair binding to ARE-containing
FT transcripts, recruitment of mRNA decay factors and ZFP36-
FT mediated deadenylation and decay of ARE-containing
FT transcripts; when associated with A-178."
FT /evidence="ECO:0000269|PubMed:15014438,
FT ECO:0000269|PubMed:16508014, ECO:0000269|PubMed:16508015,
FT ECO:0000269|PubMed:17170118, ECO:0000269|PubMed:20595389,
FT ECO:0000269|PubMed:21078877"
FT MUTAGEN 64..66
FT /note="PPP->SSS: Abolished interaction with GIGYF2 and
FT impaired TTP-mediated mRNA repression; when associated with
FT 191-S--S-193."
FT /evidence="ECO:0000269|PubMed:26763119"
FT MUTAGEN 178
FT /note="S->A: Reduces both interaction with 14-3-3 proteins
FT and YWHAB-induced cytoplasmic localization. Impairs
FT phosphorylation by MAPKAPK2, decreases its stability and
FT cytoplasmic localization, increases interaction with
FT PPP2CA, inhibits binding to 14-3-3 proteins, but does not
FT impair binding to ARE-containing transcripts, recruitment
FT of mRNA decay factors and ZFP36-mediated deadenylation and
FT decay of ARE-containing transcripts; when associated with
FT A-52."
FT /evidence="ECO:0000269|PubMed:11886850,
FT ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:16508014,
FT ECO:0000269|PubMed:16508015, ECO:0000269|PubMed:17170118,
FT ECO:0000269|PubMed:20595389, ECO:0000269|PubMed:21078877"
FT MUTAGEN 191..193
FT /note="PPP->SSS: Abolished interaction with GIGYF2 and
FT impaired TTP-mediated mRNA repression; when associated with
FT 64-S--S-66."
FT /evidence="ECO:0000269|PubMed:26763119"
FT MUTAGEN 212..214
FT /note="PPP->SSS: Does not affect interaction with GIGYF2."
FT /evidence="ECO:0000269|PubMed:26763119"
FT MUTAGEN 303
FT /note="P->A: Stimulates interaction with SH3KBP1."
FT /evidence="ECO:0000269|PubMed:20221403"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:1M9O"
FT TURN 111..115
FT /evidence="ECO:0007829|PDB:1M9O"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:1M9O"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:1M9O"
SQ SEQUENCE 319 AA; 33613 MW; 860DD6DDA80386F8 CRC64;
MDLSAIYESL QSMSHDLSSD HGGTESLGGL WNINSDSIPS GVTSRLTGRS TSLVEGRSCG
WVPPPPGFAP LAPRPGPELS PSPTSPTATP TTSSRYKTEL CRTYSESGRC RYGAKCQFAH
GLGELRQANR HPKYKTELCH KFYLQGRCPY GSRCHFIHNP TEDLALPGQP HVLRQSISFS
GLPSGRRSSP PPPGFSGPSL SSCSFSPSSS PPPPGDLPLS PSAFSAAPGT PVTRRDPNQA
CCPSCRRSTT PSTIWGPLGG LARSPSAHSL GSDPDDYASS GSSLGGSDSP VFEAGVFGPP
QTPAPPRRLP IFNRISVSE
