ID TISB_HUMAN Reviewed; 338 AA. AC Q07352; Q13851; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 27-MAR-2024, entry version 203. DE RecName: Full=mRNA decay activator protein ZFP36L1 {ECO:0000305}; DE AltName: Full=Butyrate response factor 1 {ECO:0000303|PubMed:10367403, ECO:0000303|PubMed:12198173}; DE AltName: Full=EGF-response factor 1 {ECO:0000303|PubMed:8346037}; DE Short=ERF-1 {ECO:0000303|PubMed:8346037}; DE AltName: Full=TPA-induced sequence 11b {ECO:0000250|UniProtKB:P23950}; DE AltName: Full=Zinc finger protein 36, C3H1 type-like 1 {ECO:0000312|HGNC:HGNC:1107}; DE Short=ZFP36-like 1 {ECO:0000312|HGNC:HGNC:1107}; GN Name=ZFP36L1 {ECO:0000312|HGNC:HGNC:1107}; GN Synonyms=BERG36 {ECO:0000303|PubMed:8898945}, BRF1 GN {ECO:0000303|PubMed:10367403, ECO:0000303|PubMed:12198173}, ERF1 GN {ECO:0000303|PubMed:8346037}, RNF162B, TIS11B GN {ECO:0000250|UniProtKB:P23950}; 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 [MRNA]. RX PubMed=8346037; DOI=10.1093/nar/21.15.3580; RA Barnard R.C., Pascall J.C., Brown K.D., McKay I.A., Williams N.S., RA Bustin S.A.; RT "Coding sequence of ERF-1, the human homologue of Tis11b/cMG1, members of RT the Tis11 family of early response genes."; RL Nucleic Acids Res. 21:3580-3580(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8024689; DOI=10.1089/dna.1994.13.449; RA Bustin S.A., Nie X.F., Barnard R.C., Kumar V., Pascall J.C., Brown K.D., RA Leigh I.M., Williams N.S., McKay L.A.; RT "Cloning and characterization of ERF-1, a human member of the Tis11 family RT of early-response genes."; RL DNA Cell Biol. 13:449-459(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8898945; DOI=10.1002/eji.1830261013; RA Ning Z.Q., Norton J.D., Li J., Murphy J.J.; RT "Distinct mechanisms for rescue from apoptosis in Ramos human B cells by RT signaling through CD40 and interleukin-4 receptor: role for inhibition of RT an early response gene, Berg36."; RL Eur. J. Immunol. 26:2356-2363(1996). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; 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 [6] RP INDUCTION. RX PubMed=10367403; RA Maclean K.N., McKay I.A., Bustin S.A.; RT "Differential effects of sodium butyrate on the transcription of the human RT TIS11 family of early-response genes in colorectal cancer cells."; RL Br. J. Biomed. Sci. 55:184-191(1998). RN [7] RP FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-120 AND RP CYS-158. RX PubMed=12198173; DOI=10.1093/emboj/cdf444; RA Stoecklin G., Colombi M., Raineri I., Leuenberger S., Mallaun M., RA Schmidlin M., Gross B., Lu M., Kitamura T., Moroni C.; RT "Functional cloning of BRF1, a regulator of ARE-dependent mRNA turnover."; RL EMBO J. 21:4709-4718(2002). RN [8] RP TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=15465005; DOI=10.1016/j.bbrc.2004.09.030; RA Reppe S., Olstad O.K., Rian E., Gautvik V.T., Gautvik K.M., Jemtland R.; RT "Butyrate response factor 1 is regulated by parathyroid hormone and bone RT morphogenetic protein-2 in osteoblastic cells."; RL Biochem. Biophys. Res. Commun. 324:218-223(2004). RN [9] RP FUNCTION, RNA-BINDING, INTERACTION WITH YWHAB, PHOSPHORYLATION AT SER-90 RP AND SER-92, AND MUTAGENESIS OF SER-90 AND SER-92. RX PubMed=15538381; DOI=10.1038/sj.emboj.7600477; RA Schmidlin M., Lu M., Leuenberger S.A., Stoecklin G., Mallaun M., Gross B., RA Gherzi R., Hess D., Hemmings B.A., Moroni C.; RT "The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by RT protein kinase B."; RL EMBO J. 23:4760-4769(2004). RN [10] RP FUNCTION, AND RNA-BINDING. RX PubMed=15467755; DOI=10.1038/sj.onc.1207939; RA Ciais D., Cherradi N., Bailly S., Grenier E., Berra E., Pouyssegur J., RA Lamarre J., Feige J.J.; RT "Destabilization of vascular endothelial growth factor mRNA by the zinc- RT finger protein TIS11b."; RL Oncogene 23:8673-8680(2004). RN [11] 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 [12] 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 [13] RP FUNCTION, RNA-BINDING, INTERACTION WITH YWHAB, PHOSPHORYLATION AT SER-203, RP UBIQUITINATION, AND MUTAGENESIS OF SER-92 AND SER-203. RX PubMed=17030608; DOI=10.1128/mcb.01099-06; RA Benjamin D., Schmidlin M., Min L., Gross B., Moroni C.; RT "BRF1 protein turnover and mRNA decay activity are regulated by protein RT kinase B at the same phosphorylation sites."; RL Mol. Cell. Biol. 26:9497-9507(2006). RN [14] RP FUNCTION, AND SUBCELLULAR LOCATION. 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 [15] RP FUNCTION, INTERACTION WITH CNOT6; DCP2; EXOSC2 AND YWHAB, PHOSPHORYLATION RP AT SER-54; SER-92 AND SER-203, AND MUTAGENESIS OF SER-54; SER-92 AND RP SER-203. RX PubMed=18326031; DOI=10.1261/rna.983708; RA Maitra S., Chou C.F., Luber C.A., Lee K.Y., Mann M., Chen C.Y.; RT "The AU-rich element mRNA decay-promoting activity of BRF1 is regulated by RT mitogen-activated protein kinase-activated protein kinase 2."; RL RNA 14:950-959(2008). RN [16] RP FUNCTION, RNA-BINDING, PHOSPHORYLATION, AND INDUCTION. RX PubMed=19179481; DOI=10.1210/me.2008-0296; RA Duan H., Cherradi N., Feige J.J., Jefcoate C.; RT "cAMP-dependent posttranscriptional regulation of steroidogenic acute RT regulatory (STAR) protein by the zinc finger protein ZFP36L1/TIS11b."; RL Mol. Endocrinol. 23:497-509(2009). RN [17] 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 [18] 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 [19] RP FUNCTION, RNA-BINDING, AND INDUCTION. RX PubMed=21832157; DOI=10.1091/mbc.e11-02-0149; RA Desroches-Castan A., Cherradi N., Feige J.J., Ciais D.; RT "A novel function of Tis11b/BRF1 as a regulator of Dll4 mRNA 3'-end RT processing."; RL Mol. Biol. Cell 22:3625-3633(2011). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54, AND IDENTIFICATION BY RP 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54, AND IDENTIFICATION BY RP 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 [22] RP FUNCTION, RNA-BINDING, AND MUTAGENESIS OF CYS-120 AND CYS-158. RX PubMed=24700863; DOI=10.1681/asn.2013091023; RA Viengchareun S., Lema I., Lamribet K., Keo V., Blanchard A., Cherradi N., RA Lombes M.; RT "Hypertonicity compromises renal mineralocorticoid receptor signaling RT through Tis11b-mediated post-transcriptional control."; RL J. Am. Soc. Nephrol. 25:2213-2221(2014). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54 AND SER-318, AND 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 [24] RP FUNCTION, RNA-BINDING, INTERACTION WITH CNOT1 AND CNOT7, PHOSPHORYLATION AT RP SER-334, MUTAGENESIS OF SER-334 AND SER-336, AND IDENTIFICATION BY MASS RP SPECTROMETRY. 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 [25] RP FUNCTION, AND RNA-BINDING. RX PubMed=25014217; DOI=10.1371/journal.pone.0102625; RA Zekavati A., Nasir A., Alcaraz A., Aldrovandi M., Marsh P., Norton J.D., RA Murphy J.J.; RT "Post-transcriptional regulation of BCL2 mRNA by the RNA-binding protein RT ZFP36L1 in malignant B cells."; RL PLoS ONE 9:E102625-E102625(2014). RN [26] RP FUNCTION, RNA-BINDING, AND INDUCTION. RX PubMed=26542173; DOI=10.1038/srep16229; RA Chen M.T., Dong L., Zhang X.H., Yin X.L., Ning H.M., Shen C., Su R., Li F., RA Song L., Ma Y.N., Wang F., Zhao H.L., Yu J., Zhang J.W.; RT "ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6."; RL Sci. Rep. 5:16229-16229(2015). RN [27] RP FUNCTION, 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 [28] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 325-333 IN COMPLEX WITH MAJOR RP HISTOCOMPATIBILITY COMPLEX HLA. RX PubMed=15713487; DOI=10.1016/j.jmb.2004.12.047; RA Hulsmeyer M., Welfle K., Pohlmann T., Misselwitz R., Alexiev U., Welfle H., RA Saenger W., Uchanska-Ziegler B., Ziegler A.; RT "Thermodynamic and structural equivalence of two HLA-B27 subtypes complexed RT with a self-peptide."; RL J. Mol. Biol. 346:1367-1379(2005). 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:12198173, CC PubMed:15538381, PubMed:15467755, PubMed:17030608, PubMed:19179481, CC PubMed:20702587, PubMed:24700863, PubMed:25106868, PubMed:25014217, CC PubMed:26542173). Acts as a 3'-untranslated region (UTR) ARE mRNA- CC binding adapter protein to communicate signaling events to the mRNA CC decay machinery (PubMed:15687258). Functions by recruiting the CCR4-NOT CC deadenylase complex and components of the cytoplasmic RNA decay CC machinery to the bound ARE-containing mRNAs, and hence promotes ARE- CC mediated mRNA deadenylation and decay processes (PubMed:15687258, CC PubMed:18326031, PubMed:25106868). Induces also the degradation of ARE- CC containing mRNAs even in absence of poly(A) tail (By similarity). Binds CC to 3'-UTR ARE of numerous mRNAs (PubMed:12198173, PubMed:15538381, CC PubMed:15467755, PubMed:17030608, PubMed:19179481, PubMed:20702587, CC PubMed:24700863, PubMed:25106868, PubMed:25014217, PubMed:26542173). CC Positively regulates early adipogenesis by promoting ARE-mediated mRNA CC decay of immediate early genes (IEGs) (By similarity). Promotes ARE- CC mediated mRNA decay of mineralocorticoid receptor NR3C2 mRNA in CC response to hypertonic stress (PubMed:24700863). Negatively regulates CC hematopoietic/erythroid cell differentiation by promoting ARE-mediated CC mRNA decay of the transcription factor STAT5B mRNA (PubMed:20702587). CC Positively regulates monocyte/macrophage cell differentiation by CC promoting ARE-mediated mRNA decay of the cyclin-dependent kinase CDK6 CC mRNA (PubMed:26542173). Promotes degradation of ARE-containing CC pluripotency-associated mRNAs in embryonic stem cells (ESCs), such as CC NANOG, through a fibroblast growth factor (FGF)-induced MAPK-dependent CC signaling pathway, and hence attenuates ESC self-renewal and positively CC regulates mesendoderm differentiation (By similarity). May play a role CC in mediating pro-apoptotic effects in malignant B-cells by promoting CC ARE-mediated mRNA decay of BCL2 mRNA (PubMed:25014217). In association CC with ZFP36L2 maintains quiescence on developing B lymphocytes by CC promoting ARE-mediated decay of several mRNAs encoding cell cycle CC regulators that help B cells progress through the cell cycle, and hence CC ensuring accurate variable-diversity-joining (VDJ) recombination and CC functional immune cell formation (By similarity). Together with ZFP36L2 CC is also necessary for thymocyte development and prevention of T-cell CC acute lymphoblastic leukemia (T-ALL) transformation by promoting ARE- CC mediated mRNA decay of the oncogenic transcription factor NOTCH1 mRNA CC (By similarity). Participates in the delivery of target ARE-mRNAs to CC processing bodies (PBs) (PubMed:17369404). In addition to its cytosolic CC mRNA-decay function, plays a role in the regulation of nuclear mRNA 3'- CC end processing; modulates mRNA 3'-end maturation efficiency of the DLL4 CC mRNA through binding with an ARE embedded in a weak noncanonical CC polyadenylation (poly(A)) signal in endothelial cells CC (PubMed:21832157). Also involved in the regulation of stress granule CC (SG) and P-body (PB) formation and fusion (PubMed:15967811). Plays a CC role in vasculogenesis and endocardial development (By similarity). CC Plays a role in the regulation of keratinocyte proliferation, CC differentiation and apoptosis (PubMed:27182009). Plays a role in CC myoblast cell differentiation (By similarity). CC {ECO:0000250|UniProtKB:P17431, ECO:0000250|UniProtKB:P23950, CC ECO:0000269|PubMed:12198173, ECO:0000269|PubMed:15467755, CC ECO:0000269|PubMed:15538381, ECO:0000269|PubMed:15687258, CC ECO:0000269|PubMed:15967811, ECO:0000269|PubMed:17030608, CC ECO:0000269|PubMed:17369404, ECO:0000269|PubMed:18326031, CC ECO:0000269|PubMed:19179481, ECO:0000269|PubMed:20702587, CC ECO:0000269|PubMed:21832157, ECO:0000269|PubMed:24700863, CC ECO:0000269|PubMed:25014217, ECO:0000269|PubMed:25106868, CC ECO:0000269|PubMed:26542173, ECO:0000269|PubMed:27182009}. CC -!- SUBUNIT: Associates with the cytoplasmic CCR4-NOT deadenylase and RNA CC exosome complexes to trigger ARE-containing mRNA deadenylation and CC decay processes (PubMed:15687258, PubMed:18326031, PubMed:25106868). CC Interacts with CNOT1 (PubMed:25106868). Interacts (via N-terminus) with CC CNOT6 (PubMed:15687258, PubMed:18326031). Interacts with CNOT7; this CC interaction is inhibited in response to phorbol 12-myristate 13-acetate CC (PMA) treatment in a p38 MAPK-dependent manner (PubMed:25106868). CC Interacts with DCP1A (PubMed:15687258). Interacts (via N-terminus) with CC DCP2 (PubMed:15687258, PubMed:18326031). Interacts (via N-terminus) CC with EXOSC2 (PubMed:15687258, PubMed:18326031). Interacts with XRN1 CC (PubMed:15687258). Interacts (via phosphorylated form) with YWHAB; this CC interaction occurs in a protein kinase AKT1-dependent manner CC (PubMed:15538381, PubMed:17030608, PubMed:18326031). Interacts (via CC phosphorylated form) with YWHAZ; this interaction occurs in a p38 CC MAPK- and AKT-signaling pathways (By similarity). CC {ECO:0000250|UniProtKB:P23950, ECO:0000269|PubMed:12198173, CC ECO:0000269|PubMed:15467755, ECO:0000269|PubMed:15538381, CC ECO:0000269|PubMed:15687258, ECO:0000269|PubMed:15967811, CC ECO:0000269|PubMed:17030608, ECO:0000269|PubMed:17369404, CC ECO:0000269|PubMed:18326031, ECO:0000269|PubMed:19179481, CC ECO:0000269|PubMed:20702587, ECO:0000269|PubMed:21832157, CC ECO:0000269|PubMed:24700863, ECO:0000269|PubMed:25014217, CC ECO:0000269|PubMed:25106868, ECO:0000269|PubMed:26542173, CC ECO:0000269|PubMed:27182009}. CC -!- INTERACTION: CC Q07352; Q16539: MAPK14; NbExp=2; IntAct=EBI-721823, EBI-73946; CC Q07352; P61981: YWHAG; NbExp=4; IntAct=EBI-721823, EBI-359832; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12198173}. Cytoplasm CC {ECO:0000269|PubMed:12198173}. Cytoplasmic granule CC {ECO:0000269|PubMed:15967811}. Cytoplasm, P-body CC {ECO:0000269|PubMed:15967811, ECO:0000269|PubMed:17369404}. CC Note=Shuttles between the nucleus and the cytoplasm in a XPO1/CRM1- CC dependent manner (By similarity). Component of cytoplasmic stress CC granules (PubMed:15967811). Localizes in processing bodies (PBs) CC (PubMed:17369404). {ECO:0000250|UniProtKB:P23950, CC ECO:0000269|PubMed:15967811, ECO:0000269|PubMed:17369404}. CC -!- TISSUE SPECIFICITY: Expressed mainly in the basal epidermal layer, CC weakly in the suprabasal epidermal layers (PubMed:27182009). Expressed CC in epidermal keratinocytes (at protein level) (PubMed:27182009). CC Expressed in osteoblasts (PubMed:15465005). CC {ECO:0000269|PubMed:15465005, ECO:0000269|PubMed:27182009}. CC -!- INDUCTION: Down-regulated under hypoxic conditions in endothelial cells CC (at protein level) (PubMed:21832157). Up-regulated by growth factor CC (TGF-beta), cytokines, tumor necrosis factor (TNF-alpha) and epidermal CC growth factor (EGF) in keratinocytes (PubMed:20166898). Up-regulated CC also by glucocorticoid dexamethasone in keratinocytes CC (PubMed:20166898). Up-regulated in keratinocytes in response to CC wounding in a p38 MAPK-dependent manner (PubMed:20166898, CC PubMed:27182009). Up-regulated by the parathyroid hormone (PTH) in CC osteoblast-like cells in a cAMP/PKA-dependent manner (PubMed:15465005, CC PubMed:19179481). Up-regulated in response to adrenocorticotropic CC hormone (ACTH) (PubMed:19179481). Up-regulated during CC monocyte/macrophage differentiation in response to phorbol ester 12-O- CC tetradecanoylphorbol-13-acetate (TPA) (PubMed:26542173). Down-regulated CC by butyrate in colorectal cancer cells (PubMed:10367403). CC {ECO:0000269|PubMed:10367403, ECO:0000269|PubMed:15465005, CC ECO:0000269|PubMed:19179481, ECO:0000269|PubMed:20166898, CC ECO:0000269|PubMed:21832157, ECO:0000269|PubMed:26542173, CC ECO:0000269|PubMed:27182009}. CC -!- PTM: Phosphorylated (PubMed:19179481). Phosphorylated by RPS6KA1 at CC Ser-334 upon phorbol 12-myristate 13-acetate (PMA) treatment; this CC phosphorylation results in dissociation of the CCR4-NOT deadenylase CC complex and induces p38 MAPK-mediated stabilization of the low-density CC lipoprotein receptor LDLR mRNA (PubMed:25106868). Phosphorylated by CC protein kinase AKT1 at Ser-92 and Ser-203 in response to insulin; these CC phosphorylations stabilize ZFP36L1, increase the association with 14-3- CC 3 proteins and mediate ARE-containing mRNA stabilization CC (PubMed:15538381, PubMed:17030608). AKT1-mediated phosphorylation at CC Ser-92 does not impair ARE-containing RNA-binding (PubMed:15538381). CC Phosphorylated at Ser-54, Ser-92 and Ser-203 by MAPKAPK2; these CC phosphorylations increase the association with 14-3-3 proteins and CC mediate ARE-containing mRNA stabilization in a protein kinase AKT1- CC independent manner (PubMed:18326031). MAPKAPK2-mediated CC phosphorylations at Ser-54, Ser-92 and Ser-203 do not impair ARE- CC containing RNA-binding (PubMed:18326031). Phosphorylations increase the CC association with 14-3-3 proteins and mediate ARE-containing mRNA CC stabilization during early adipogenesis in a p38 MAPK- and AKT- CC dependent manner (By similarity). {ECO:0000250|UniProtKB:P23950, CC ECO:0000269|PubMed:15538381, ECO:0000269|PubMed:17030608, CC ECO:0000269|PubMed:18326031, ECO:0000269|PubMed:19179481, CC ECO:0000269|PubMed:25106868}. CC -!- PTM: Ubiquitinated. Ubiquitination leads to proteasomal degradation, a CC process inhibited by phosphorylations at Ser-90, Ser-92 and Ser-203 CC (PubMed:17030608). {ECO:0000269|PubMed:17030608}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42866/ZFP36L1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X79066; CAA55670.1; -; mRNA. DR EMBL; X79067; CAA55670.1; JOINED; mRNA. DR EMBL; X99404; CAA67781.1; -; mRNA. DR EMBL; BT019468; AAV38275.1; -; mRNA. DR EMBL; BC018340; AAH18340.1; -; mRNA. DR CCDS; CCDS9791.1; -. DR PIR; S34854; S34854. DR RefSeq; NP_001231627.1; NM_001244698.1. DR RefSeq; NP_001231630.1; NM_001244701.1. DR RefSeq; NP_004917.2; NM_004926.3. DR PDB; 1W0V; X-ray; 2.27 A; C=325-333. DR PDB; 1W0W; X-ray; 2.10 A; C=325-333. DR PDBsum; 1W0V; -. DR PDBsum; 1W0W; -. DR AlphaFoldDB; Q07352; -. DR SMR; Q07352; -. DR BioGRID; 107144; 30. DR CORUM; Q07352; -. DR IntAct; Q07352; 48. DR MINT; Q07352; -. DR STRING; 9606.ENSP00000337386; -. DR iPTMnet; Q07352; -. DR PhosphoSitePlus; Q07352; -. DR BioMuta; ZFP36L1; -. DR DMDM; 1351254; -. DR EPD; Q07352; -. DR jPOST; Q07352; -. DR MassIVE; Q07352; -. DR MaxQB; Q07352; -. DR PaxDb; 9606-ENSP00000388402; -. DR PeptideAtlas; Q07352; -. DR ProteomicsDB; 58515; -. DR Pumba; Q07352; -. DR Antibodypedia; 37; 420 antibodies from 34 providers. DR DNASU; 677; -. DR Ensembl; ENST00000336440.4; ENSP00000337386.3; ENSG00000185650.10. DR Ensembl; ENST00000439696.3; ENSP00000388402.2; ENSG00000185650.10. DR GeneID; 677; -. DR KEGG; hsa:677; -. DR MANE-Select; ENST00000439696.3; ENSP00000388402.2; NM_004926.4; NP_004917.2. DR UCSC; uc001xkh.3; human. DR AGR; HGNC:1107; -. DR CTD; 677; -. DR DisGeNET; 677; -. DR GeneCards; ZFP36L1; -. DR HGNC; HGNC:1107; ZFP36L1. DR HPA; ENSG00000185650; Low tissue specificity. DR MIM; 601064; gene. DR neXtProt; NX_Q07352; -. DR OpenTargets; ENSG00000185650; -. DR PharmGKB; PA35027; -. DR VEuPathDB; HostDB:ENSG00000185650; -. DR eggNOG; KOG1677; Eukaryota. DR GeneTree; ENSGT00940000155076; -. DR HOGENOM; CLU_033040_1_0_1; -. DR InParanoid; Q07352; -. DR OMA; TPYFFRP; -. DR OrthoDB; 23913at2759; -. DR PhylomeDB; Q07352; -. DR TreeFam; TF315463; -. DR PathwayCommons; Q07352; -. DR Reactome; R-HSA-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA. DR SignaLink; Q07352; -. DR SIGNOR; Q07352; -. DR BioGRID-ORCS; 677; 141 hits in 1188 CRISPR screens. DR ChiTaRS; ZFP36L1; human. DR EvolutionaryTrace; Q07352; -. DR GeneWiki; ZFP36L1; -. DR GenomeRNAi; 677; -. DR Pharos; Q07352; Tbio. DR PRO; PR:Q07352; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q07352; Protein. DR Bgee; ENSG00000185650; Expressed in mucosa of paranasal sinus and 202 other cell types or tissues. DR ExpressionAtlas; Q07352; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. 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:0003677; F:DNA binding; IEA:UniProtKB-KW. 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:MGI. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0061158; P:3'-UTR-mediated mRNA destabilization; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl. DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl. DR GO; GO:0071320; P:cellular response to cAMP; 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; ISS:UniProtKB. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IDA:UniProtKB. DR GO; GO:0071456; P:cellular response to hypoxia; IMP:UniProtKB. DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB. DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IDA:UniProtKB. DR GO; GO:0097403; P:cellular response to raffinose; ISS:UniProtKB. DR GO; GO:0071472; P:cellular response to salt stress; ISS:UniProtKB. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:UniProtKB. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB. DR GO; GO:0060710; P:chorio-allantoic fusion; IEA:Ensembl. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; IDA:UniProtKB. DR GO; GO:0048382; P:mesendoderm development; ISS:UniProtKB. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:0051028; P:mRNA transport; IMP:UniProtKB. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0045647; P:negative regulation of erythrocyte differentiation; IDA:UniProtKB. DR GO; GO:1901991; P:negative regulation of mitotic cell cycle phase transition; ISS:UniProtKB. DR GO; GO:0021915; P:neural tube development; IEA:Ensembl. DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IEA:Ensembl. DR GO; GO:0031086; P:nuclear-transcribed mRNA catabolic process, deadenylation-independent decay; ISS:UniProtKB. DR GO; GO:0038066; P:p38MAPK cascade; ISS:UniProtKB. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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:0045657; P:positive regulation of monocyte differentiation; IDA:UniProtKB. DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; ISS:UniProtKB. DR GO; GO:0003342; P:proepicardium development; IEA:Ensembl. DR GO; GO:0045577; P:regulation of B cell differentiation; ISS:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; 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:0031440; P:regulation of mRNA 3'-end processing; IDA:UniProtKB. DR GO; GO:0043488; P:regulation of mRNA stability; IDA:UniProtKB. DR GO; GO:0045661; P:regulation of myoblast differentiation; ISS:UniProtKB. DR GO; GO:0072091; P:regulation of stem cell proliferation; ISS:UniProtKB. DR GO; GO:0006417; P:regulation of translation; IEA:Ensembl. DR GO; GO:0009611; P:response to wounding; IDA:UniProtKB. DR GO; GO:0060712; P:spongiotrophoblast layer development; IEA:Ensembl. DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB. DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl. DR Gene3D; 4.10.1000.10; Zinc finger, CCCH-type; 2. DR InterPro; IPR007635; Tis11B_N. DR InterPro; IPR045877; ZFP36-like. DR InterPro; IPR000571; Znf_CCCH. DR InterPro; IPR036855; Znf_CCCH_sf. DR PANTHER; PTHR12547; CCCH ZINC FINGER/TIS11-RELATED; 1. DR PANTHER; PTHR12547:SF53; MRNA DECAY ACTIVATOR PROTEIN ZFP36L1; 1. DR Pfam; PF04553; Tis11B_N; 1. DR Pfam; PF00642; zf-CCCH; 2. DR SMART; SM00356; ZnF_C3H1; 2. DR SUPFAM; SSF90229; CCCH zinc finger; 2. DR PROSITE; PS50103; ZF_C3H1; 2. DR Genevisible; Q07352; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Developmental protein; DNA-binding; Metal-binding; KW mRNA processing; mRNA transport; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Ribonucleoprotein; RNA-binding; Transport; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..338 FT /note="mRNA decay activator protein ZFP36L1" FT /id="PRO_0000089167" FT ZN_FING 114..142 FT /note="C3H1-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723" FT ZN_FING 152..180 FT /note="C3H1-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723" FT REGION 1..111 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 93..113 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 185..338 FT /note="Necessary for mRNA decay activation" FT /evidence="ECO:0000269|PubMed:15687258" FT REGION 273..338 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 289..338 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 54 FT /note="Phosphoserine; by MAPKAPK2" FT /evidence="ECO:0000269|PubMed:18326031, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 90 FT /note="Phosphoserine; by PKB/AKT1" FT /evidence="ECO:0000269|PubMed:15538381" FT MOD_RES 92 FT /note="Phosphoserine; by PKB/AKT1 and MAPKAPK2" FT /evidence="ECO:0000269|PubMed:15538381, FT ECO:0000269|PubMed:18326031" FT MOD_RES 203 FT /note="Phosphoserine; by PKB/AKT1 and MAPKAPK2" FT /evidence="ECO:0000269|PubMed:17030608, FT ECO:0000269|PubMed:18326031" FT MOD_RES 318 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 334 FT /note="Phosphoserine; by RPS6KA1" FT /evidence="ECO:0000269|PubMed:25106868" FT MUTAGEN 54 FT /note="S->A: Inhibits MAPKAPK2-mediated ARE-containing mRNA FT stabilization; when associated with A-92 and A-203." FT /evidence="ECO:0000269|PubMed:18326031" FT MUTAGEN 90 FT /note="S->A: Inhibits interaction with 14-3-3 proteins and FT AKT1-mediated ARE-containing mRNA stabilization, but does FT not affect ARE binding; when associated with A-92." FT /evidence="ECO:0000269|PubMed:15538381" FT MUTAGEN 92 FT /note="S->A: Inhibits MAPKAPK2-mediated ARE-containing mRNA FT stabilization; when associated with A-54 and A-203. FT Inhibits interaction with 14-3-3 proteins and AKT1-mediated FT ARE-containing mRNA stabilization; when associated with FT A-203. Inhibits interaction with 14-3-3 proteins and FT AKT1-mediated ARE-containing mRNA stabilization, but does FT not affect ARE binding; when associated with A-90." FT /evidence="ECO:0000269|PubMed:15538381, FT ECO:0000269|PubMed:17030608, ECO:0000269|PubMed:18326031" FT MUTAGEN 120 FT /note="C->R: Reduces binding to ARE-containing mRNAs and FT ARE-mediated mRNA decay. Inhibits binding to ARE-containing FT mRNAs and ARE-mediated mRNA decay; when associated with FT R-158." FT /evidence="ECO:0000269|PubMed:12198173, FT ECO:0000269|PubMed:24700863" FT MUTAGEN 158 FT /note="C->R: Reduces binding to ARE-containing mRNAs and FT ARE-mediated mRNA decay. Inhibits binding to ARE-containing FT mRNAs and ARE-mediated mRNA decay; when associated with FT R-120." FT /evidence="ECO:0000269|PubMed:12198173, FT ECO:0000269|PubMed:24700863" FT MUTAGEN 203 FT /note="S->A: Inhibits interaction with 14-3-3 proteins and FT AKT1-mediated ARE-containing mRNA stabilization; when FT associated with A-92. Inhibits MAPKAPK2-mediated FT ARE-containing mRNA stabilization; when associated with FT A-54 and A-92." FT /evidence="ECO:0000269|PubMed:17030608, FT ECO:0000269|PubMed:18326031" FT MUTAGEN 334 FT /note="S->A: Inhibits p38 MAPK-mediated LDLR mRNA FT stabilization, but does not inhibit interaction with CNOT1 FT and CNOT7; when associated with A-336." FT /evidence="ECO:0000269|PubMed:25106868" FT MUTAGEN 336 FT /note="S->A: Inhibits p38 MAPK-mediated LDLR mRNA FT stabilization, but does not inhibit interaction with CNOT1 FT and CNOT7; when associated with A-334." FT /evidence="ECO:0000269|PubMed:25106868" FT CONFLICT 63 FT /note="H -> R (in Ref. 3; CAA67781)" FT /evidence="ECO:0000305" SQ SEQUENCE 338 AA; 36314 MW; 98236CD40C4531D2 CRC64; MTTTLVSATI FDLSEVLCKG NKMLNYSAPS AGGCLLDRKA VGTPAGGGFP RRHSVTLPSS KFHQNQLLSS LKGEPAPALS SRDSRFRDRS FSEGGERLLP TQKQPGGGQV NSSRYKTELC RPFEENGACK YGDKCQFAHG IHELRSLTRH PKYKTELCRT FHTIGFCPYG PRCHFIHNAE ERRALAGARD LSADRPRLQH SFSFAGFPSA AATAAATGLL DSPTSITPPP ILSADDLLGS PTLPDGTNNP FAFSSQELAS LFAPSMGLPG GGSPTTFLFR PMSESPHMFD SPPSPQDSLS DQEGYLSSSS SSHSGSDSPT LDNSRRLPIF SRLSISDD //