TTP_HUMAN
ID TTP_HUMAN Reviewed; 326 AA.
AC P26651; B2RA54;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=mRNA decay activator protein ZFP36 {ECO:0000305};
DE AltName: Full=G0/G1 switch regulatory protein 24;
DE AltName: Full=Growth factor-inducible nuclear protein NUP475 {ECO:0000305};
DE AltName: Full=Tristetraprolin {ECO:0000303|PubMed:2062660};
DE AltName: Full=Zinc finger protein 36 {ECO:0000312|HGNC:HGNC:12862};
DE Short=Zfp-36 {ECO:0000250|UniProtKB:P22893};
GN Name=ZFP36 {ECO:0000312|HGNC:HGNC:12862};
GN Synonyms=G0S24, NUP475 {ECO:0000250|UniProtKB:P22893}, RNF162A, TIS11A,
GN TTP {ECO:0000303|PubMed:2062660};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=2062660; DOI=10.1093/nar/19.12.3454;
RA Taylor G.A., Lai W.S., Oakey R.J., Seldin M.F., Shows T.B., Eddy R.L. Jr.,
RA Blackshear P.J.;
RT "The human TTP protein: sequence, alignment with related proteins, and
RT chromosomal localization of the mouse and human genes.";
RL Nucleic Acids Res. 19:3454-3454(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-37; PHE-259 AND
RP PHE-324.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [5]
RP FUNCTION, AND RNA-BINDING.
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 [6]
RP FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF
RP CYS-124 AND CYS-147.
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 [7]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=10751406; DOI=10.1074/jbc.m001696200;
RA Lai W.S., Carballo E., Thorn J.M., Kennington E.A., Blackshear P.J.;
RT "Interactions of CCCH zinc finger proteins with mRNA. Binding of
RT tristetraprolin-related zinc finger proteins to Au-rich elements and
RT destabilization of mRNA.";
RL J. Biol. Chem. 275:17827-17837(2000).
RN [8]
RP FUNCTION, AND ASSOCIATION WITH THE RNA EXOSOME COMPLEX.
RX PubMed=11719186; DOI=10.1016/s0092-8674(01)00578-5;
RA Chen C.-Y., Gherzi R., Ong S.-E., Chan E.L., Raijmakers R., Pruijn G.J.M.,
RA Stoecklin G., Moroni C., Mann M., Karin M.;
RT "AU binding proteins recruit the exosome to degrade ARE-containing mRNAs.";
RL Cell 107:451-464(2001).
RN [9]
RP FUNCTION.
RX PubMed=11279239; DOI=10.1074/jbc.m100680200;
RA Lai W.S., Blackshear P.J.;
RT "Interactions of CCCH zinc finger proteins with mRNA: tristetraprolin-
RT mediated AU-rich element-dependent mRNA degradation can occur in the
RT absence of a poly(A) tail.";
RL J. Biol. Chem. 276:23144-23154(2001).
RN [10]
RP FUNCTION, RNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=12115244; DOI=10.1002/art.10235;
RA Brooks S.A., Connolly J.E., Diegel R.J., Fava R.A., Rigby W.F.;
RT "Analysis of the function, expression, and subcellular distribution of
RT human tristetraprolin.";
RL Arthritis Rheum. 46:1362-1370(2002).
RN [11]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH HTLV-1 TAX (MICROBIAL
RP INFECTION), AND SUBCELLULAR LOCATION (MICROBIAL INFECTION).
RX PubMed=14679154; DOI=10.1093/jnci/djg118;
RA Twizere J.-C., Kruys V., Lefebvre L., Vanderplasschen A., Collete D.,
RA Debacq C., Lai W.S., Jauniaux J.-C., Bernstein L.R., Semmes J.O., Burny A.,
RA Blackshear P.J., Kettmann R., Willems L.;
RT "Interaction of retroviral Tax oncoproteins with tristetraprolin and
RT regulation of tumor necrosis factor-alpha expression.";
RL J. Natl. Cancer Inst. 95:1846-1859(2003).
RN [12]
RP FUNCTION, RNA-BINDING, AND MUTAGENESIS OF CYS-124.
RX PubMed=12748283; DOI=10.1128/mcb.23.11.3798-3812.2003;
RA Lai W.S., Kennington E.A., Blackshear P.J.;
RT "Tristetraprolin and its family members can promote the cell-free
RT deadenylation of AU-rich element-containing mRNAs by poly(A)
RT ribonuclease.";
RL Mol. Cell. Biol. 23:3798-3812(2003).
RN [13]
RP INTERACTION WITH NUP214, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=14766228; DOI=10.1016/j.bbrc.2004.01.080;
RA Carman J.A., Nadler S.G.;
RT "Direct association of tristetraprolin with the nucleoporin CAN/Nup214.";
RL Biochem. Biophys. Res. Commun. 315:445-449(2004).
RN [14]
RP SUBCELLULAR LOCATION.
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 [15]
RP FUNCTION, RNA-BINDING, AND INDUCTION.
RX PubMed=15187101; DOI=10.4049/jimmunol.172.12.7263;
RA Brooks S.A., Connolly J.E., Rigby W.F.;
RT "The role of mRNA turnover in the regulation of tristetraprolin expression:
RT evidence for an extracellular signal-regulated kinase-specific, AU-rich
RT element-dependent, autoregulatory pathway.";
RL J. Immunol. 172:7263-7271(2004).
RN [16]
RP FUNCTION, AND INTERACTION WITH AGO2 AND AGO4.
RX PubMed=15766526; DOI=10.1016/j.cell.2004.12.038;
RA Jing Q., Huang S., Guth S., Zarubin T., Motoyama A., Chen J., Di Padova F.,
RA Lin S.C., Gram H., Han J.;
RT "Involvement of microRNA in AU-rich element-mediated mRNA instability.";
RL Cell 120:623-634(2005).
RN [17]
RP FUNCTION, IDENTIFICATION IN A MRNA DECAY ACTIVATION COMPLEX, AND
RP INTERACTION WITH CNOT6; DCP1A; DCP2; EXOSC2 AND XRN1.
RX PubMed=15687258; DOI=10.1101/gad.1282305;
RA Lykke-Andersen J., Wagner E.;
RT "Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay
RT activation domains in the proteins TTP and BRF-1.";
RL Genes Dev. 19:351-361(2005).
RN [18]
RP FUNCTION, RNA-BINDING, AND INDUCTION.
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 [19]
RP FUNCTION, INTERACTION WITH DCP2 AND EDC3, AND MUTAGENESIS OF PHE-126.
RX PubMed=16364915; DOI=10.1016/j.molcel.2005.10.031;
RA Fenger-Groen M., Fillman C., Norrild B., Lykke-Andersen J.;
RT "Multiple processing body factors and the ARE binding protein TTP activate
RT mRNA decapping.";
RL Mol. Cell 20:905-915(2005).
RN [20]
RP INTERACTION WITH KHSRP.
RX PubMed=16126846; DOI=10.1093/nar/gki797;
RA Linker K., Pautz A., Fechir M., Hubrich T., Greeve J., Kleinert H.;
RT "Involvement of KSRP in the post-transcriptional regulation of human iNOS
RT expression-complex interplay of KSRP with TTP and HuR.";
RL Nucleic Acids Res. 33:4813-4827(2005).
RN [21]
RP PHOSPHORYLATION AT SER-66; SER-88; THR-92; SER-169; SER-186; SER-197;
RP SER-218; SER-228; SER-276 AND SER-296.
RX PubMed=16262601; DOI=10.1042/bj20051316;
RA Cao H., Deterding L.J., Venable J.D., Kennington E.A., Yates J.R. III,
RA Tomer K.B., Blackshear P.J.;
RT "Identification of the anti-inflammatory protein tristetraprolin as a
RT hyperphosphorylated protein by mass spectrometry and site-directed
RT mutagenesis.";
RL Biochem. J. 394:285-297(2006).
RN [22]
RP INDUCTION.
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 [23]
RP FUNCTION, RNA-BINDING, AND MUTAGENESIS OF CYS-124.
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 [24]
RP FUNCTION, RNA-BINDING, INTERACTION WITH 14-3-3 PROTEINS, AND
RP PHOSPHORYLATION.
RX PubMed=16702957; DOI=10.1038/sj.onc.1209645;
RA Marderosian M., Sharma A., Funk A.P., Vartanian R., Masri J., Jo O.D.,
RA Gera J.F.;
RT "Tristetraprolin regulates Cyclin D1 and c-Myc mRNA stability in response
RT to rapamycin in an Akt-dependent manner via p38 MAPK signaling.";
RL Oncogene 25:6277-6290(2006).
RN [25]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-124.
RX PubMed=17369404; DOI=10.1101/gad.1494707;
RA Franks T.M., Lykke-Andersen J.;
RT "TTP and BRF proteins nucleate processing body formation to silence mRNAs
RT with AU-rich elements.";
RL Genes Dev. 21:719-735(2007).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [27]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18367721; DOI=10.1261/rna.748408;
RA Emmons J., Townley-Tilson W.H., Deleault K.M., Skinner S.J., Gross R.H.,
RA Whitfield M.L., Brooks S.A.;
RT "Identification of TTP mRNA targets in human dendritic cells reveals TTP as
RT a critical regulator of dendritic cell maturation.";
RL RNA 14:888-902(2008).
RN [28]
RP RNA-BINDING, AND MUTAGENESIS OF CYS-124.
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 [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [30]
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 [31]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=20702587; DOI=10.1091/mbc.e10-01-0040;
RA Vignudelli T., Selmi T., Martello A., Parenti S., Grande A., Gemelli C.,
RA Zanocco-Marani T., Ferrari S.;
RT "ZFP36L1 negatively regulates erythroid differentiation of CD34+
RT hematopoietic stem cells by interfering with the Stat5b pathway.";
RL Mol. Biol. Cell 21:3340-3351(2010).
RN [32]
RP FUNCTION, INTERACTION WITH HEAT SHOCK 70 KDA PROTEINS; MAP3K4; NCL; PABPC1
RP AND SH3KBP1, PHOSPHORYLATION AT SER-66 AND SER-93, RNA-BINDING, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF PRO-309.
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 [33]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=21775632; DOI=10.1091/mbc.e10-07-0617;
RA Chamboredon S., Ciais D., Desroches-Castan A., Savi P., Bono F.,
RA Feige J.J., Cherradi N.;
RT "Hypoxia-inducible factor-1alpha mRNA: a new target for destabilization by
RT tristetraprolin in endothelial cells.";
RL Mol. Biol. Cell 22:3366-3378(2011).
RN [34]
RP MUTAGENESIS OF PHE-126.
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [36]
RP INTERACTION WITH PRR5L.
RX PubMed=21964062; DOI=10.1016/j.cellsig.2011.09.015;
RA Holmes B., Artinian N., Anderson L., Martin J., Masri J., Cloninger C.,
RA Bernath A., Bashir T., Benavides-Serrato A., Gera J.;
RT "Protor-2 interacts with tristetraprolin to regulate mRNA stability during
RT stress.";
RL Cell. Signal. 24:309-315(2012).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93; SER-186 AND SER-323, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [39]
RP INTERACTION WITH CNOT7.
RX PubMed=25106868; DOI=10.1093/nar/gku652;
RA Adachi S., Homoto M., Tanaka R., Hioki Y., Murakami H., Suga H.,
RA Matsumoto M., Nakayama K.I., Hatta T., Iemura S., Natsume T.;
RT "ZFP36L1 and ZFP36L2 control LDLR mRNA stability via the ERK-RSK pathway.";
RL Nucleic Acids Res. 42:10037-10049(2014).
RN [40]
RP FUNCTION, RNA-BINDING, AND MUTAGENESIS OF PHE-126.
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.
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 FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=27182009; DOI=10.1016/j.ejcb.2016.04.007;
RA Prenzler F., Fragasso A., Schmitt A., Munz B.;
RT "Functional analysis of ZFP36 proteins in keratinocytes.";
RL Eur. J. Cell Biol. 95:277-284(2016).
RN [43]
RP FUNCTION, INTERACTION WITH PKM, PHOSPHORYLATION, UBIQUITINATION, AND
RP MUTAGENESIS OF SER-60.
RX PubMed=26926077; DOI=10.1038/srep22449;
RA Huang L., Yu Z., Zhang Z., Ma W., Song S., Huang G.;
RT "Interaction with pyruvate kinase M2 destabilizes tristetraprolin by
RT proteasome degradation and regulates cell proliferation in breast cancer.";
RL Sci. Rep. 6:22449-22449(2016).
RN [44]
RP FUNCTION.
RX PubMed=31439631; DOI=10.1101/gad.329219.119;
RA Peter D., Ruscica V., Bawankar P., Weber R., Helms S., Valkov E.,
RA Igreja C., Izaurralde E.;
RT "Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated
RT translational repression.";
RL Genes Dev. 33:1355-1360(2019).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 312-326 IN COMPLEX WITH CNOT1,
RP INTERACTION WITH CNOT1, FUNCTION, AND MUTAGENESIS OF ARG-315 AND PHE-319.
RX PubMed=23644599; DOI=10.1038/nsmb.2572;
RA Fabian M.R., Frank F., Rouya C., Siddiqui N., Lai W.S., Karetnikov A.,
RA Blackshear P.J., Nagar B., Sonenberg N.;
RT "Structural basis for the recruitment of the human CCR4-NOT deadenylase
RT complex by tristetraprolin.";
RL Nat. Struct. Mol. Biol. 20:735-739(2013).
CC -!- FUNCTION: Zinc-finger RNA-binding protein that destabilizes several
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:9703499,
CC PubMed:10330172, PubMed:10751406, PubMed:11279239, PubMed:12115244,
CC PubMed:12748283, PubMed:15187101, PubMed:15634918, PubMed:17030620,
CC PubMed:16702957, PubMed:20702587, PubMed:20221403, PubMed:21775632,
CC PubMed:27193233, PubMed:23644599, PubMed:25815583, PubMed:31439631).
CC Acts as an 3'-untranslated region (UTR) ARE mRNA-binding adapter
CC protein to communicate signaling events to the mRNA decay machinery
CC (PubMed:15687258, PubMed:23644599). Recruits deadenylase CNOT7 (and
CC probably the CCR4-NOT complex) via association with CNOT1, and hence
CC promotes ARE-mediated mRNA deadenylation (PubMed:23644599). Functions
CC also by recruiting components of the cytoplasmic RNA decay machinery to
CC the bound ARE-containing mRNAs (PubMed:11719186, PubMed:12748283,
CC PubMed:15687258, PubMed:16364915). Self regulates by destabilizing its
CC own mRNA (PubMed:15187101). Binds to 3'-UTR ARE of numerous mRNAs and
CC of its own mRNA (PubMed:10330172, PubMed:10751406, PubMed:12115244,
CC PubMed:15187101, PubMed:15634918, PubMed:17030620, PubMed:16702957,
CC PubMed:19188452, PubMed:20702587, PubMed:20221403, PubMed:21775632,
CC PubMed:25815583). 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 (By similarity). Also plays a role in the
CC regulation of dendritic cell maturation at the post-transcriptional
CC level, and hence operates as part of a negative feedback loop to limit
CC the inflammatory response (PubMed:18367721). Promotes ARE-mediated mRNA
CC decay of hypoxia-inducible factor HIF1A mRNA during the response of
CC endothelial cells to hypoxia (PubMed:21775632). Positively regulates
CC early adipogenesis of preadipocytes by promoting ARE-mediated mRNA
CC decay of immediate early genes (IEGs) (By similarity). Negatively
CC regulates hematopoietic/erythroid cell differentiation by promoting
CC ARE-mediated mRNA decay of the transcription factor STAT5B mRNA
CC (PubMed:20702587). Plays a role in maintaining skeletal muscle
CC satellite cell quiescence by promoting ARE-mediated mRNA decay of the
CC myogenic determination factor MYOD1 mRNA (By similarity). Associates
CC also with and regulates the expression of non-ARE-containing target
CC mRNAs at the post-transcriptional level, such as MHC class I mRNAs
CC (PubMed:18367721). Participates in association with argonaute RISC
CC catalytic components in the ARE-mediated mRNA decay mechanism; assists
CC microRNA (miRNA) targeting ARE-containing mRNAs (PubMed:15766526). May
CC also play a role in the regulation of cytoplasmic mRNA decapping;
CC enhances decapping of ARE-containing RNAs, in vitro (PubMed:16364915).
CC Involved in the delivery of target ARE-mRNAs to processing bodies (PBs)
CC (PubMed:17369404). In addition to its cytosolic mRNA-decay function,
CC affects nuclear pre-mRNA processing (By similarity). Negatively
CC regulates nuclear poly(A)-binding protein PABPN1-stimulated
CC polyadenylation activity on ARE-containing pre-mRNA during LPS-
CC stimulated macrophages (By similarity). Also involved in the regulation
CC of stress granule (SG) and P-body (PB) formation and fusion (By
CC similarity). Plays a role in the regulation of keratinocyte
CC proliferation, differentiation and apoptosis (PubMed:27182009). Plays a
CC role as a tumor suppressor by inhibiting cell proliferation in breast
CC cancer cells (PubMed:26926077). {ECO:0000250|UniProtKB:P22893,
CC ECO:0000269|PubMed:10330172, ECO:0000269|PubMed:10751406,
CC ECO:0000269|PubMed:11279239, ECO:0000269|PubMed:11719186,
CC ECO:0000269|PubMed:12115244, ECO:0000269|PubMed:12748283,
CC ECO:0000269|PubMed:15187101, ECO:0000269|PubMed:15634918,
CC ECO:0000269|PubMed:15687258, ECO:0000269|PubMed:15766526,
CC ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:16702957,
CC ECO:0000269|PubMed:17030620, ECO:0000269|PubMed:17369404,
CC ECO:0000269|PubMed:18367721, ECO:0000269|PubMed:19188452,
CC ECO:0000269|PubMed:20221403, ECO:0000269|PubMed:20702587,
CC ECO:0000269|PubMed:21775632, ECO:0000269|PubMed:23644599,
CC ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:26926077,
CC ECO:0000269|PubMed:27182009, ECO:0000269|PubMed:27193233,
CC ECO:0000269|PubMed:31439631, ECO:0000269|PubMed:9703499}.
CC -!- FUNCTION: (Microbial infection) Negatively regulates HTLV-1 TAX-
CC dependent transactivation of viral long terminal repeat (LTR) promoter.
CC {ECO:0000269|PubMed:14679154}.
CC -!- SUBUNIT: Associates with cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase
CC complexes to trigger ARE-containing mRNA deadenylation and decay
CC processes (By similarity). Part of a mRNA decay activation complex at
CC least composed of poly(A)-specific exoribonucleases CNOT6, EXOSC2 and
CC XRN1 and mRNA-decapping enzymes DCP1A and DCP2 (PubMed:15687258).
CC Associates with the RNA exosome complex (PubMed:11719186). Interacts
CC (via phosphorylated form) with 14-3-3 proteins; these interactions
CC promote exclusion of ZFP36 from cytoplasmic stress granules in response
CC to arsenite treatment in a MAPKAPK2-dependent manner and does not
CC prevent CCR4-NOT deadenylase complex recruitment or ZFP36-induced ARE-
CC containing mRNA deadenylation and decay processes (By similarity).
CC Interacts with 14-3-3 proteins; these interactions occur in response to
CC rapamycin in an Akt-dependent manner (PubMed:16702957). Interacts with
CC AGO2 and AGO4 (PubMed:15766526). Interacts (via C-terminus) with CNOT1;
CC this interaction occurs in a RNA-independent manner and induces mRNA
CC deadenylation (PubMed:23644599). Interacts (via N-terminus) with CNOT6
CC (PubMed:15687258). Interacts with CNOT6L (By similarity). 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:25106868). Interacts
CC (via unphosphorylated form) with CNOT8; this interaction occurs in a
CC RNA-independent manner and is inhibited in a phosphorylation MAPKAPK2-
CC dependent manner (By similarity). Interacts with DCP1A
CC (PubMed:15687258). Interacts (via N-terminus) with DCP2
CC (PubMed:15687258, PubMed:16364915). Interacts with EDC3
CC (PubMed:16364915). Interacts (via N-terminus) with EXOSC2
CC (PubMed:15687258). Interacts with heat shock 70 kDa proteins
CC (PubMed:20221403). Interacts with KHSRP; this interaction increases
CC upon cytokine-induced treatment (PubMed:16126846). Interacts with
CC MAP3K4; this interaction enhances the association with SH3KBP1/CIN85
CC (PubMed:20221403). Interacts with MAPKAPK2; this interaction occurs
CC upon skeletal muscle satellite cell activation (By similarity).
CC Interacts with NCL (PubMed:20221403). Interacts with NUP214; this
CC interaction increases upon lipopolysaccharide (LPS) stimulation
CC (PubMed:14766228). Interacts with PABPC1; this interaction occurs in a
CC RNA-dependent manner (PubMed:20221403). Interacts (via
CC hypophosphorylated form) with PABPN1 (via RRM domain and C-terminal
CC arginine-rich region); this interaction occurs in the nucleus in a RNA-
CC independent manner, decreases in presence of single-stranded poly(A)
CC RNA-oligomer and in a p38 MAPK-dependent-manner and inhibits nuclear
CC poly(A) tail synthesis (By similarity). Interacts with PAN2 (By
CC similarity). Interacts (via C3H1-type zinc finger domains) with PKM
CC (PubMed:26926077). Interacts (via C3H1-type zinc finger domains) with
CC nuclear RNA poly(A) polymerase (By similarity). Interacts with PPP2CA;
CC this interaction occurs in LPS-stimulated cells and induces ZFP36
CC dephosphorylation, and hence may promote ARE-containing mRNAs decay (By
CC similarity). Interacts (via C-terminus) with PRR5L (via C-terminus);
CC this interaction may accelerate ZFP36-mediated mRNA decay during stress
CC (PubMed:21964062). Interacts (via C-terminus) with SFN; this
CC interaction occurs in a phosphorylation-dependent manner (By
CC similarity). Interacts (via extreme C-terminal region) with
CC SH3KBP1/CIN85 (via SH3 domains); this interaction enhances MAP3K4-
CC induced phosphorylation of ZFP36 at Ser-66 and Ser-93 and does not
CC alter neither ZFP36 binding to ARE-containing transcripts nor TNF-alpha
CC mRNA decay (PubMed:20221403). Interacts with XRN1 (PubMed:15687258).
CC Interacts (via C-terminus and Ser-186 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-186
CC dephosphorylation by serine/threonine phosphatase 2A, and hence may be
CC crucial for stabilizing ARE-containing mRNAs (By similarity). Interacts
CC (via phosphorylated form) with YWHAE (By similarity). Interacts (via C-
CC terminus) with YWHAG; this interaction occurs in a phosphorylation-
CC dependent manner (By similarity). Interacts with YWHAH; this
CC interaction occurs in a phosphorylation-dependent manner (By
CC similarity). Interacts with YWHAQ; this interaction occurs in a
CC phosphorylation-dependent manner (By similarity). Interacts with (via
CC C-terminus) YWHAZ; this interaction occurs in a phosphorylation-
CC dependent manner (By similarity). Interacts (via P-P-P-P-G repeats)
CC with GIGYF2; the interaction is direct (By similarity).
CC {ECO:0000250|UniProtKB:P22893, ECO:0000269|PubMed:11719186,
CC ECO:0000269|PubMed:14766228, ECO:0000269|PubMed:15687258,
CC ECO:0000269|PubMed:15766526, ECO:0000269|PubMed:16126846,
CC ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:16702957,
CC ECO:0000269|PubMed:20221403, ECO:0000269|PubMed:21964062,
CC ECO:0000269|PubMed:23644599, ECO:0000269|PubMed:25106868,
CC ECO:0000269|PubMed:26926077}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via C-terminus) with HTLV-1
CC TAX (via C-terminus); this interaction inhibits HTLV-1 TAX to
CC transactivate viral long terminal repeat (LTR) promoter
CC (PubMed:14679154). {ECO:0000269|PubMed:14679154}.
CC -!- INTERACTION:
CC P26651; A5YKK6-2: CNOT1; NbExp=4; IntAct=EBI-374248, EBI-16057352;
CC P26651; Q9NPI6: DCP1A; NbExp=2; IntAct=EBI-374248, EBI-374238;
CC P26651; Q96F86: EDC3; NbExp=2; IntAct=EBI-374248, EBI-997311;
CC P26651; Q13643: FHL3; NbExp=4; IntAct=EBI-374248, EBI-741101;
CC P26651; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-374248, EBI-1055254;
CC P26651; P16284: PECAM1; NbExp=3; IntAct=EBI-374248, EBI-716404;
CC P26651; Q06455-2: RUNX1T1; NbExp=3; IntAct=EBI-374248, EBI-11984663;
CC P26651; P08670: VIM; NbExp=3; IntAct=EBI-374248, EBI-353844;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15014438,
CC ECO:0000269|PubMed:27182009}. Cytoplasm {ECO:0000269|PubMed:10330172,
CC ECO:0000269|PubMed:12115244, ECO:0000269|PubMed:14766228,
CC ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:20221403}. Cytoplasmic
CC granule {ECO:0000269|PubMed:15014438}. Cytoplasm, P-body
CC {ECO:0000269|PubMed:17369404}. Note=Shuttles between nucleus and
CC cytoplasm in a CRM1-dependent manner (By similarity). Localized
CC predominantly in the cytoplasm in a p38 MAPK- and YWHAB-dependent
CC manner (By similarity). Colocalizes with SH3KBP1 and MAP3K4 in the
CC cytoplasm (PubMed:20221403). Component of cytoplasmic stress granules
CC (SGs) (By similarity). Localizes to cytoplasmic stress granules upon
CC energy starvation (PubMed:15014438). Localizes in processing bodies
CC (PBs) (PubMed:17369404). Excluded from stress granules in a
CC phosphorylation MAPKAPK2-dependent manner (By similarity). Shuttles in
CC and out of both cytoplasmic P-body and SGs (By similarity).
CC {ECO:0000250|UniProtKB:P22893, ECO:0000269|PubMed:15014438,
CC ECO:0000269|PubMed:17369404, ECO:0000269|PubMed:20221403}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14679154}. Cytoplasm
CC {ECO:0000269|PubMed:14679154}. Note=(Microbial infection) Colocalizes
CC with HTLV-1 TAX in the nucleus and the cytoplasm in a region
CC surrounding the nucleus. {ECO:0000269|PubMed:14679154}.
CC -!- TISSUE SPECIFICITY: Expressed in both basal and suprabasal epidermal
CC layers (PubMed:27182009). Expressed in epidermal keratinocytes
CC (PubMed:27182009). Expressed strongly in mature dendritic cells
CC (PubMed:18367721). Expressed in immature dendritic cells (at protein
CC level) (PubMed:18367721). {ECO:0000269|PubMed:18367721,
CC ECO:0000269|PubMed:27182009}.
CC -!- INDUCTION: Up-regulated by T cell activation (PubMed:15634918). Up-
CC regulated in keratinocytes in response to wounding (PubMed:27182009).
CC Up-regulated by lipopolysaccharide (LPS) in a p38 MAPK- and ERK-
CC dependent manner (at protein level) (PubMed:15187101, PubMed:16508015).
CC Up-regulated strongly during epidermal repair after wounding in
CC keratinocytes (PubMed:20166898). Up-regulated strongly by epidermal
CC growth factor (EGF) and tumor necrosis factor (TNF-alpha) in
CC keratinocytes (PubMed:20166898). Up-regulated moderately by granulocyte
CC macrophage colony-stimulating factor (GM-CSF) and fibroblast growth
CC factor (FGF1) in keratinocytes (PubMed:20166898). Up-regulated also by
CC glucocorticoid dexamethasone in keratinocytes (PubMed:20166898). Up-
CC regulated in keratinocytes in response to wounding (PubMed:27182009).
CC Up-regulated by LPS in a p38 MAPK-dependent manner (PubMed:14766228,
CC PubMed:15187101). {ECO:0000269|PubMed:14766228,
CC ECO:0000269|PubMed:15187101, ECO:0000269|PubMed:15634918,
CC ECO:0000269|PubMed:16508015, ECO:0000269|PubMed:20166898,
CC ECO:0000269|PubMed:27182009}.
CC -!- DOMAIN: The C3H1-type zinc finger domains are necessary for ARE-binding
CC activity (PubMed:10330172). {ECO:0000269|PubMed:10330172}.
CC -!- PTM: Phosphorylated. Phosphorylation at serine and/or threonine
CC residues occurs in a p38 MAPK- and MAPKAPK2-dependent manner
CC (PubMed:16702957). Phosphorylated by MAPKAPK2 at Ser-60 and Ser-186;
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. Phosphorylation by
CC MAPKAPK2 does not impair ARE-containing RNA-binding. Phosphorylated in
CC a MAPKAPK2- and p38 MAPK-dependent manner upon skeletal muscle
CC satellite cell activation; this phosphorylation inhibits ZFP36-mediated
CC mRNA decay activity, and hence stabilizes MYOD1 mRNA (By similarity).
CC Phosphorylated by MAPK1 upon mitogen stimulation (By similarity).
CC Phosphorylated at Ser-66 and Ser-93; these phosphorylations increase in
CC a SH3KBP1-dependent manner (PubMed:20221403). Phosphorylated at serine
CC and threonine residues in a pyruvate kinase PKM- and p38 MAPK-dependent
CC manner (PubMed:26926077). Phosphorylation at Ser-60 may participate in
CC the PKM-mediated degradation of ZFP36 in a p38 MAPK-dependent manner
CC (PubMed:26926077). Dephosphorylated by serine/threonine phosphatase 2A
CC at Ser-186 (By similarity). {ECO:0000250|UniProtKB:P22893,
CC ECO:0000269|PubMed:16702957, ECO:0000269|PubMed:20221403,
CC ECO:0000269|PubMed:26926077}.
CC -!- PTM: Ubiquitinated; pyruvate kinase (PKM)-dependent ubiquitination
CC leads to proteasomal degradation through a p38 MAPK signaling pathway
CC (PubMed:26926077). {ECO:0000269|PubMed:26926077}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/zfp36/";
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DR EMBL; M92843; AAA58489.1; -; mRNA.
DR EMBL; M92844; AAC37600.1; -; Genomic_DNA.
DR EMBL; M63625; AAA61240.1; -; mRNA.
DR EMBL; AK314042; BAG36751.1; -; mRNA.
DR EMBL; AY771351; AAV28731.1; -; Genomic_DNA.
DR EMBL; BC009693; AAH09693.1; -; mRNA.
DR CCDS; CCDS12534.2; -.
DR PIR; S34427; S34427.
DR RefSeq; NP_003398.2; NM_003407.3.
DR PDB; 4J8S; X-ray; 1.55 A; B=312-326.
DR PDBsum; 4J8S; -.
DR AlphaFoldDB; P26651; -.
DR SMR; P26651; -.
DR BioGRID; 113370; 173.
DR CORUM; P26651; -.
DR DIP; DIP-29845N; -.
DR IntAct; P26651; 31.
DR STRING; 9606.ENSP00000469647; -.
DR iPTMnet; P26651; -.
DR PhosphoSitePlus; P26651; -.
DR BioMuta; ZFP36; -.
DR DMDM; 136471; -.
DR EPD; P26651; -.
DR jPOST; P26651; -.
DR MassIVE; P26651; -.
DR PaxDb; P26651; -.
DR PeptideAtlas; P26651; -.
DR PRIDE; P26651; -.
DR ProteomicsDB; 54360; -.
DR Antibodypedia; 1121; 382 antibodies from 26 providers.
DR DNASU; 7538; -.
DR Ensembl; ENST00000597629.3; ENSP00000469647.2; ENSG00000128016.7.
DR GeneID; 7538; -.
DR KEGG; hsa:7538; -.
DR MANE-Select; ENST00000597629.3; ENSP00000469647.2; NM_003407.5; NP_003398.3.
DR CTD; 7538; -.
DR DisGeNET; 7538; -.
DR GeneCards; ZFP36; -.
DR HGNC; HGNC:12862; ZFP36.
DR HPA; ENSG00000128016; Low tissue specificity.
DR MIM; 190700; gene.
DR neXtProt; NX_P26651; -.
DR OpenTargets; ENSG00000128016; -.
DR PharmGKB; PA37451; -.
DR VEuPathDB; HostDB:ENSG00000128016; -.
DR eggNOG; KOG1677; Eukaryota.
DR GeneTree; ENSGT00940000162360; -.
DR InParanoid; P26651; -.
DR OMA; WGLARSP; -.
DR OrthoDB; 1541140at2759; -.
DR PhylomeDB; P26651; -.
DR TreeFam; TF315463; -.
DR PathwayCommons; P26651; -.
DR Reactome; R-HSA-450513; Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA.
DR SignaLink; P26651; -.
DR SIGNOR; P26651; -.
DR BioGRID-ORCS; 7538; 32 hits in 1099 CRISPR screens.
DR ChiTaRS; ZFP36; human.
DR GeneWiki; ZFP36; -.
DR GenomeRNAi; 7538; -.
DR Pharos; P26651; Tbio.
DR PRO; PR:P26651; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P26651; protein.
DR Bgee; ENSG00000128016; Expressed in vena cava and 205 other tissues.
DR ExpressionAtlas; P26651; baseline and differential.
DR GO; GO:0030014; C:CCR4-NOT complex; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; IDA:UniProtKB.
DR GO; GO:0019957; F:C-C chemokine binding; IPI:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0031072; F:heat shock protein binding; IDA:UniProtKB.
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:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0070063; F:RNA polymerase binding; ISS:UniProtKB.
DR GO; GO:0061158; P:3'-UTR-mediated mRNA destabilization; IDA:UniProtKB.
DR GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; IDA:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA: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; IDA:UniProtKB.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IDA: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; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IMP:UniProtKB.
DR GO; GO:0030099; P:myeloid cell differentiation; IEA:Ensembl.
DR GO; GO:0045647; P:negative regulation of erythrocyte differentiation; IDA:UniProtKB.
DR GO; GO:1902037; P:negative regulation of hematopoietic stem cell differentiation; IEA:Ensembl.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; ISS:UniProtKB.
DR GO; GO:1904246; P:negative regulation of polynucleotide adenylyltransferase activity; ISS: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; IMP:UniProtKB.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IDA:UniProtKB.
DR GO; GO:0031086; P:nuclear-transcribed mRNA catabolic process, deadenylation-independent decay; IDA:UniProtKB.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IMP:BHF-UCL.
DR GO; GO:0038066; P:p38MAPK cascade; ISS:UniProtKB.
DR GO; GO:1901835; P:positive regulation of deadenylation-independent decapping of nuclear-transcribed mRNA; IDA:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:1904582; P:positive regulation of intracellular mRNA localization; IMP:UniProtKB.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; 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; IMP:UniProtKB.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0010837; P:regulation of keratinocyte proliferation; IMP:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IDA:UniProtKB.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0042594; P:response to starvation; IDA:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IDA:UniProtKB.
DR IDEAL; IID00655; -.
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; DNA-binding; Exosome; Host-virus interaction;
KW Metal-binding; mRNA transport; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Ribonucleoprotein; RNA-binding; RNA-mediated gene silencing;
KW Transport; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..326
FT /note="mRNA decay activator protein ZFP36"
FT /id="PRO_0000089163"
FT REPEAT 71..75
FT /note="P-P-P-P-G"
FT REPEAT 198..202
FT /note="P-P-P-P-G"
FT REPEAT 219..223
FT /note="P-P-P-P-G"
FT ZN_FING 103..131
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 141..169
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 1..174
FT /note="Necessary for localization of ARE-containing mRNAs
FT to processing bodies (PBs)"
FT /evidence="ECO:0000269|PubMed:17369404"
FT REGION 1..100
FT /note="Necessary and sufficient for the association with
FT mRNA decay enzymes and mRNA decay activation"
FT /evidence="ECO:0000269|PubMed:15687258"
FT REGION 1..15
FT /note="Necessary for nuclear export"
FT /evidence="ECO:0000250|UniProtKB:P47973"
FT REGION 13..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..168
FT /note="Necessary for nuclear localization"
FT /evidence="ECO:0000250|UniProtKB:P47973"
FT REGION 97..173
FT /note="Necessary for RNA-binding"
FT /evidence="ECO:0000269|PubMed:10751406,
FT ECO:0000269|PubMed:12748283"
FT REGION 100..326
FT /note="Necessary for localization of ARE-containing mRNAs
FT to processing bodies (PBs)"
FT /evidence="ECO:0000269|PubMed:17369404"
FT REGION 103..194
FT /note="Necessary for interaction with PABPN1"
FT /evidence="ECO:0000250|UniProtKB:P22893"
FT REGION 174..326
FT /note="Necessary for mRNA decay activation"
FT /evidence="ECO:0000269|PubMed:15687258"
FT REGION 175..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 273..292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..326
FT /note="Interaction with CNOT1"
FT /evidence="ECO:0000269|PubMed:23644599"
FT COMPBIAS 27..59
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 60
FT /note="Phosphoserine; by MAPKAPK2"
FT /evidence="ECO:0000250|UniProtKB:P22893"
FT MOD_RES 66
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16262601,
FT ECO:0000269|PubMed:20221403"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16262601"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22893"
FT MOD_RES 92
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16262601"
FT MOD_RES 93
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20221403,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16262601"
FT MOD_RES 186
FT /note="Phosphoserine; by MAPKAPK2"
FT /evidence="ECO:0000269|PubMed:16262601,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16262601"
FT MOD_RES 218
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16262601"
FT MOD_RES 228
FT /note="Phosphoserine; by MAPK1; in vitro"
FT /evidence="ECO:0000269|PubMed:16262601"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16262601"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16262601"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 37
FT /note="P -> S (in dbSNP:rs17878633)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021064"
FT VARIANT 55
FT /note="P -> S (in dbSNP:rs2229272)"
FT /id="VAR_052324"
FT VARIANT 259
FT /note="I -> F (in dbSNP:rs17886974)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021065"
FT VARIANT 324
FT /note="V -> F (in dbSNP:rs17884899)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021066"
FT MUTAGEN 60
FT /note="S->A: Inhibits PKM-induced ZFP36 degradation through
FT a p38 MAPK signaling pathway."
FT /evidence="ECO:0000269|PubMed:26926077"
FT MUTAGEN 124
FT /note="C->R: Inhibits binding to ARE-containing
FT transcripts. Inhibits binding to and deadenylation
FT activities of ARE-containing mRNAs. Inhibits localization
FT of ARE-containing mRNAs to processing bodies (PBs)."
FT /evidence="ECO:0000269|PubMed:10330172,
FT ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:17030620,
FT ECO:0000269|PubMed:17369404, ECO:0000269|PubMed:19188452"
FT MUTAGEN 126
FT /note="F->N: Inhibits ARE-containing RNA-binding,
FT deadenylation and RNA decapping activities."
FT /evidence="ECO:0000269|PubMed:16364915,
FT ECO:0000269|PubMed:21078877, ECO:0000269|PubMed:25815583"
FT MUTAGEN 147
FT /note="C->R: Inhibits both ARE-binding and mRNA
FT deadenylation activities."
FT /evidence="ECO:0000269|PubMed:10330172"
FT MUTAGEN 309
FT /note="P->V: Inhibits interaction with SH3KBP1."
FT /evidence="ECO:0000269|PubMed:20221403"
FT MUTAGEN 315
FT /note="R->A: Abolishes interaction with CNOT1."
FT /evidence="ECO:0000269|PubMed:23644599"
FT MUTAGEN 319
FT /note="F->A: Abolishes interaction with CNOT1 and impairs
FT TNF mRNA deadenylation."
FT /evidence="ECO:0000269|PubMed:23644599"
FT HELIX 317..322
FT /evidence="ECO:0007829|PDB:4J8S"
SQ SEQUENCE 326 AA; 34003 MW; DDD9AD950AF7AF98 CRC64;
MDLTAIYESL LSLSPDVPVP SDHGGTESSP GWGSSGPWSL SPSDSSPSGV TSRLPGRSTS
LVEGRSCGWV PPPPGFAPLA PRLGPELSPS PTSPTATSTT PSRYKTELCR TFSESGRCRY
GAKCQFAHGL GELRQANRHP KYKTELCHKF YLQGRCPYGS RCHFIHNPSE DLAAPGHPPV
LRQSISFSGL PSGRRTSPPP PGLAGPSLSS SSFSPSSSPP PPGDLPLSPS AFSAAPGTPL
ARRDPTPVCC PSCRRATPIS VWGPLGGLVR TPSVQSLGSD PDEYASSGSS LGGSDSPVFE
AGVFAPPQPV AAPRRLPIFN RISVSE
