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Protein

mRNA decay activator protein ZFP36L1

Gene

Zfp36l1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:22701344, PubMed:24700863, PubMed:24733888, PubMed:27102483). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (By similarity). Functions by recruiting the CCR4-NOT deadenylating complex and components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes (By similarity). Induces also the degradation of ARE-containing mRNAs even in absence of poly(A) tail (By similarity). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:22701344, PubMed:24700863, PubMed:24733888). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (PubMed:22701344). Promotes ARE-mediated mRNA decay of mineralocorticoid receptor NR3C2 mRNA in response to hypertonic stress (PubMed:24700863). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA (By similarity). Positively regulates monocyte/macrophage cell differentiation by promoting ARE-mediated mRNA decay of the cyclin-dependent kinase CDK6 mRNA (By similarity). Promotes degradation of ARE-containing pluripotency-associated mRNAs in embryonic stem cells (ESCs), such as NANOG, through a fibroblast growth factor (FGF)-induced MAPK-dependent signaling pathway, and hence attenuates ESC self-renewal and positively regulates mesendoderm differentiation (PubMed:24733888). May play a role in mediating pro-apoptotic effects in malignant B-cells by promoting ARE-mediated mRNA decay of BCL2 mRNA (By similarity). In association with ZFP36L2 maintains quiescence on developing B lymphocytes by promoting ARE-mediated decay of several mRNAs encoding cell cycle regulators that help B cells progress through the cell cycle, and hence ensuring accurate variable-diversity-joining (VDJ) recombination and functional immune cell formation (PubMed:27102483). Together with ZFP36L2 is also necessary for thymocyte development and prevention of T-cell acute lymphoblastic leukemia (T-ALL) transformation by promoting ARE-mediated mRNA decay of the oncogenic transcription factor NOTCH1 mRNA (PubMed:20622884). Involved in the delivery of target ARE-mRNAs to processing bodies (PBs) (By similarity). In addition to its cytosolic mRNA-decay function, plays a role in the regulation of nuclear mRNA 3'-end processing; modulates mRNA 3'-end maturation efficiency of the DLL4 mRNA through binding with an ARE embedded in a weak noncanonical polyadenylation (poly(A)) signal in endothelial cells (By similarity). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (By similarity). Plays a role in vasculogenesis and endocardial development (PubMed:15226444, PubMed:17013884). Involved in the regulation of keratinocyte proliferation, differentiation and apoptosis (By similarity). Plays a role in myoblast cell differentiation (PubMed:17889962).By similarity8 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri114 – 142C3H1-type 1PROSITE-ProRule annotationAdd BLAST29
Zinc fingeri152 – 180C3H1-type 2PROSITE-ProRule annotationAdd BLAST29

GO - Molecular functioni

  • 14-3-3 protein binding Source: UniProtKB
  • AU-rich element binding Source: MGI
  • DNA binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • mRNA 3'-UTR AU-rich region binding Source: UniProtKB
  • mRNA 3'-UTR binding Source: GO_Central
  • mRNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA

Names & Taxonomyi

Protein namesi
Recommended name:
mRNA decay activator protein ZFP36L1Curated
Alternative name(s):
Butyrate response factor 1By similarity
TPA-induced sequence 11b1 Publication
Zinc finger protein 36, C3H1 type-like 1Imported
Short name:
ZFP36-like 1Imported
Gene namesi
Name:Zfp36l1Imported
Synonyms:Brf1By similarity, Tis11b1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:107946 Zfp36l1

Subcellular locationi

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryos die in utero at 11 dpc (PubMed:15226444, PubMed:17013884). Exhibit extraembryonic, intraembryonic, vascular and neural tube defects and cardiac abnormalities at 9.5 dpc (PubMed:17013884). Show a reduced number of circulating blood cells (PubMed:17013884). Show failure of chorioallantoic fusion (PubMed:15226444). Exhibited increased level of VEGFA protein level in embryonic fibroblasts under both normoxic and hypoxic conditions (PubMed:17013884). Knockout mice lacking both ZFP36L1 and ZFP36L2 during thymopoiesis lead to aberrant T cell development and subsequently develop a T-cell acute lymphoblastic leukemia (T-ALL) (PubMed:20622884). Show also higher levels of NOTCH1 protein and mRNA in thymocytes (PubMed:20622884). Conditional knockout mice of both ZFP36L1 and ZFP36L2 in pro-B cells display reduced B lymphocyte number and delayed variable-diversity-joining (VDJ) recombination (PubMed:27102483). Exhibit also increased protein and ARE-containing mRNA expressions of several factors implicated in cell cycle progression in late pre-B cells (PubMed:27102483).4 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000891681 – 338mRNA decay activator protein ZFP36L1Add BLAST338

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei54Phosphoserine; by MAPKAPK2By similarity1
Modified residuei90Phosphoserine; by PKB/AKT1By similarity1
Modified residuei92Phosphoserine; by PKB/AKT1 and MAPKAPK2By similarity1
Modified residuei203Phosphoserine; by PKB/AKT1 and MAPKAPK2By similarity1
Modified residuei318PhosphoserineBy similarity1
Modified residuei334Phosphoserine; by RPS6KA1By similarity1

Post-translational modificationi

Phosphorylated (PubMed:19179481). Phosphorylated by RPS6KA1 at Ser-334 upon phorbol 12-myristate 13-acetate (PMA) treatment; this phosphorylation results in dissociation of the CCR4-NOT deadenylase complex and induces p38 MAPK-mediated stabilization of the low-density lipoprotein receptor LDLR mRNA. Phosphorylated by protein kinase AKT1 at Ser-92 and Ser-203 in response to insulin; these phosphorylations stabilize ZFP36L1, increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization. AKT1-mediated phosphorylation at Ser-92 does not impair ARE-containing RNA-binding. Phosphorylated at Ser-54, Ser-92 and Ser-203 by MAPKAPK2; these phosphorylations increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization in a protein kinase AKT1-independent manner. MAPKAPK2-mediated phosphorylations at Ser-54, Ser-92 and Ser-203 do not impair ARE-containing RNA-binding (By similarity). Phosphorylations increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization during early adipogenesis in a p38 MAPK- and AKT-dependent manner (PubMed:22701344).By similarity2 Publications
Ubiquitinated. Ubiquitination leads to proteasomal degradation, a process inhibited by phosphorylations at Ser-90, Ser-92 and Ser-203.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP23950
PeptideAtlasiP23950
PRIDEiP23950

PTM databases

iPTMnetiP23950
PhosphoSitePlusiP23950

Expressioni

Tissue specificityi

Expressed in preadipocytes and adipocytes (PubMed:22701344). Expressed in the proximal and distal tubules in the renal cortex (at protein level) (PubMed:24700863). Expressed in ovary, heart, kidney, lung, spleen and thymus (PubMed:15226444). Weakly expressed in brain, liver and testis (PubMed:15226444). Expressed in osteoblasts (PubMed:15465005). Expressed in embryonic stem cells (ESCs) (PubMed:24733888). Expressed through B lymphocyte development (PubMed:27102483).6 Publications

Developmental stagei

Expressed in embryos at 8 dpc, onward (PubMed:15226444). Expressed in the allantois and throughout the neuroectoderm and paraxial mesoderm at 8 dpc (PubMed:15226444). Expressed in the chorion and blood vessels at 8.5 dpc (PubMed:17013884). Expressed in the neural tube, paraxial mesoderm, heart, brain, otic vesicle and yolk sac at 9.5 dpc (PubMed:17013884). Expressed in embryonic stem cells (ESC) (PubMed:15226444).2 Publications

Inductioni

Up-regulated during myogenic differentiation in a p38 MAPK-dependent manner (PubMed:17889962). Up-regulated in response to fibroblast growth factor FGF4 in embryonic stem cells (ESCs) in a p38 MAPK-dependent manner (PubMed:24733888). Up-regulated during high sodium diet-fed in the renal tubules (PubMed:24700863). Up-regulated upon hypertonic stress condition with raffinose (at protein level) (PubMed:24700863). Up-regulated by parathyroid hormone (PTH) in calvarial osteoblasts (PubMed:15465005). Up-regulated in response to adrenocorticotropic hormone (ACTH) (PubMed:19179481). Up-regulated in response to cAMP (PubMed:19179481). Down-regulated by bone morphogenetic protein BMP2 treatment in calvarial osteoblasts (PubMed:15465005). Down-regulated during the conversion from quiescence to activated satellite cells upon muscle injury (PubMed:23046558, PubMed:25815583).7 Publications

Gene expression databases

BgeeiENSMUSG00000021127 Expressed in 339 organ(s), highest expression level in vas deferens
CleanExiMM_ZFP36L1
ExpressionAtlasiP23950 baseline and differential
GenevisibleiP23950 MM

Interactioni

Subunit structurei

Associates with the cytoplasmic CCR4-NOT deadenylase and RNA exosome complexes to trigger ARE-containing mRNA deadenylation and decay processes. Interacts with CNOT1. Interacts (via N-terminus) with CNOT6. Interacts with CNOT7; this interaction is inhibited in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner. Interacts with DCP1A. Interacts (via N-terminus) with DCP2. Interacts (via N-terminus) with EXOSC2. Interacts with XRN1. Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a protein kinase AKT1-dependent manner (By similarity). Interacts (via phosphorylated form) with YWHAZ; this interaction occurs in a p38 MAPK- and AKT-signaling pathways (PubMed:22701344).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198385, 1 interactor
IntActiP23950, 1 interactor
STRINGi10090.ENSMUSP00000021552

Structurei

3D structure databases

ProteinModelPortaliP23950
SMRiP23950
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 111Necessary and sufficient for the association with mRNA decay enzymes and mRNA decay activationBy similarityAdd BLAST111
Regioni185 – 338Necessary for mRNA decay activationBy similarityAdd BLAST154

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi307 – 316Poly-Ser10

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri114 – 142C3H1-type 1PROSITE-ProRule annotationAdd BLAST29
Zinc fingeri152 – 180C3H1-type 2PROSITE-ProRule annotationAdd BLAST29

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1677 Eukaryota
COG5063 LUCA
GeneTreeiENSGT00530000063262
HOGENOMiHOG000233479
HOVERGENiHBG008483
InParanoidiP23950
KOiK18753
OMAiLQHSYSF
OrthoDBiEOG091G0957
PhylomeDBiP23950
TreeFamiTF315463

Family and domain databases

InterProiView protein in InterPro
IPR007635 Tis11B_N
IPR000571 Znf_CCCH
IPR036855 Znf_CCCH_sf
PfamiView protein in Pfam
PF04553 Tis11B_N, 1 hit
PF00642 zf-CCCH, 2 hits
SMARTiView protein in SMART
SM00356 ZnF_C3H1, 2 hits
SUPFAMiSSF90229 SSF90229, 2 hits
PROSITEiView protein in PROSITE
PS50103 ZF_C3H1, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P23950-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTTTLVSATI FDLSEVLCKG NKMLNYSTPS AGGCLLDRKA VGTPAGGGFP
60 70 80 90 100
RRHSVTLPSS KFHQNQLLSS LKGEPAPSLS SRDSRFRDRS FSEGGERLLP
110 120 130 140 150
TQKQPGSGQV NSSRYKTELC RPFEENGACK YGDKCQFAHG IHELRSLTRH
160 170 180 190 200
PKYKTELCRT FHTIGFCPYG PRCHFIHNAE ERRALAGGRD LSADRPRLQH
210 220 230 240 250
SFSFAGFPSA AATAAATGLL DSPTSITPPP ILSADDLLGS PTLPDGTNNP
260 270 280 290 300
FAFSSQELAS LFAPSMGLPG GGSPTTFLFR PMSESPHMFD SPPSPQDSLS
310 320 330
DHEGYLSSSS SSHSGSDSPT LDNSRRLPIF SRLSISDD
Length:338
Mass (Da):36,385
Last modified:March 1, 1992 - v1
Checksum:iA28F2C8BF476496C
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1W2P7G3A0A1W2P7G3_MOUSE
mRNA decay activator protein ZFP36L...
Zfp36l1
84Annotation score:
A0A1W2P6I1A0A1W2P6I1_MOUSE
mRNA decay activator protein ZFP36L...
Zfp36l1
57Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M58566 mRNA Translation: AAA72948.1
CCDSiCCDS26010.1
PIRiB39590
RefSeqiNP_031590.1, NM_007564.5
UniGeneiMm.235132

Genome annotation databases

EnsembliENSMUST00000021552; ENSMUSP00000021552; ENSMUSG00000021127
ENSMUST00000165114; ENSMUSP00000127522; ENSMUSG00000021127
GeneIDi12192
KEGGimmu:12192
UCSCiuc007oal.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M58566 mRNA Translation: AAA72948.1
CCDSiCCDS26010.1
PIRiB39590
RefSeqiNP_031590.1, NM_007564.5
UniGeneiMm.235132

3D structure databases

ProteinModelPortaliP23950
SMRiP23950
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198385, 1 interactor
IntActiP23950, 1 interactor
STRINGi10090.ENSMUSP00000021552

PTM databases

iPTMnetiP23950
PhosphoSitePlusiP23950

Proteomic databases

PaxDbiP23950
PeptideAtlasiP23950
PRIDEiP23950

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021552; ENSMUSP00000021552; ENSMUSG00000021127
ENSMUST00000165114; ENSMUSP00000127522; ENSMUSG00000021127
GeneIDi12192
KEGGimmu:12192
UCSCiuc007oal.1 mouse

Organism-specific databases

CTDi677
MGIiMGI:107946 Zfp36l1

Phylogenomic databases

eggNOGiKOG1677 Eukaryota
COG5063 LUCA
GeneTreeiENSGT00530000063262
HOGENOMiHOG000233479
HOVERGENiHBG008483
InParanoidiP23950
KOiK18753
OMAiLQHSYSF
OrthoDBiEOG091G0957
PhylomeDBiP23950
TreeFamiTF315463

Enzyme and pathway databases

ReactomeiR-MMU-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA

Miscellaneous databases

ChiTaRSiZfp36l1 mouse
PROiPR:P23950
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021127 Expressed in 339 organ(s), highest expression level in vas deferens
CleanExiMM_ZFP36L1
ExpressionAtlasiP23950 baseline and differential
GenevisibleiP23950 MM

Family and domain databases

InterProiView protein in InterPro
IPR007635 Tis11B_N
IPR000571 Znf_CCCH
IPR036855 Znf_CCCH_sf
PfamiView protein in Pfam
PF04553 Tis11B_N, 1 hit
PF00642 zf-CCCH, 2 hits
SMARTiView protein in SMART
SM00356 ZnF_C3H1, 2 hits
SUPFAMiSSF90229 SSF90229, 2 hits
PROSITEiView protein in PROSITE
PS50103 ZF_C3H1, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTISB_MOUSE
AccessioniPrimary (citable) accession number: P23950
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: November 7, 2018
This is version 140 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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