TISB_HUMAN
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 03-AUG-2022, entry version 195.
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},
GN BRF1 {ECO:0000303|PubMed:10367403, ECO:0000303|PubMed:12198173},
GN ERF1 {ECO:0000303|PubMed:8346037}, RNF162B,
GN TIS11B {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 -!- 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="http://atlasgeneticsoncology.org/Genes/ZFP36L1ID42866ch14q22.html";
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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; 24.
DR CORUM; Q07352; -.
DR IntAct; Q07352; 12.
DR MINT; Q07352; -.
DR STRING; 9606.ENSP00000388402; -.
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; Q07352; -.
DR PeptideAtlas; Q07352; -.
DR PRIDE; Q07352; -.
DR ProteomicsDB; 58515; -.
DR Antibodypedia; 37; 375 antibodies from 34 providers.
DR DNASU; 677; -.
DR Ensembl; ENST00000336440.3; 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 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; 1541140at2759; -.
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; 134 hits in 1105 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 200 other tissues.
DR ExpressionAtlas; Q07352; baseline and differential.
DR Genevisible; Q07352; HS.
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:0014065; P:phosphatidylinositol 3-kinase signaling; 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:0043491; P:protein kinase B signaling; ISS:UniProtKB.
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: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 InterPro; IPR007635; Tis11B_N.
DR InterPro; IPR045877; ZFP36-like.
DR InterPro; IPR000571; Znf_CCCH.
DR InterPro; IPR036855; Znf_CCCH_sf.
DR PANTHER; PTHR12547; PTHR12547; 1.
DR Pfam; PF04553; Tis11B_N; 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; 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 A-
FT 203. Inhibits interaction with 14-3-3 proteins and AKT1-
FT mediated ARE-containing mRNA stabilization, but does not
FT 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 R-
FT 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 R-
FT 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 ARE-
FT containing mRNA stabilization; when associated with A-54
FT 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
