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Protein

mRNA decay activator protein ZFP36L1

Gene

Zfp36l1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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:10751406, PubMed:12748283). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:12748283). Functions by recruiting the CCR4-NOT deadenylase 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 (PubMed:12748283). Induces also the degradation of ARE-containing mRNAs even in absence of poly(A) tail (PubMed:11279239). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:10751406). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). Promotes ARE-mediated mRNA decay of mineralocorticoid receptor NR3C2 mRNA in response to hypertonic stress. Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA. Positively regulates monocyte/macrophage cell differentiation by promoting ARE-mediated mRNA decay of the cyclin-dependent kinase CDK6 mRNA. 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. May play a role in mediating pro-apoptotic effects in malignant B-cells by promoting ARE-mediated mRNA decay of BCL2 mRNA. 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. 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. Participates in the delivery of target ARE-mRNAs to processing bodies (PBs). 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. Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion. Plays a role in vasculogenesis and endocardial development. Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis. Plays a role in myoblast cell differentiation (By similarity).By similarity3 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: RGD
  • 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: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Ribonucleoprotein

Keywords - Biological processi

mRNA processing, mRNA transport, Transport

Keywords - Ligandi

DNA-binding, Metal-binding, RNA-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-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
EGF-inducible protein CMG1Curated
TPA-induced sequence 11bBy similarity
Zinc finger protein 36, C3H1 type-like 1Imported
Short name:
ZFP36-like 1Imported
Gene namesi
Name:Zfp36l1Imported
Synonyms:Brf1By similarity, Cmg11 Publication, Tis11b1 Publication
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi62009. Zfp36l1.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity
  • Cytoplasmic granule By similarity
  • CytoplasmP-body By similarity

  • Note: Shuttles between the nucleus and the cytoplasm in a XPO1/CRM1-dependent manner. Component of cytoplasmic stress granules. Localizes in processing bodies (PBs).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000891691 – 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 Publication1
Modified residuei203Phosphoserine; by PKB/AKT1 and MAPKAPK2By similarity1
Modified residuei318PhosphoserineBy similarity1
Modified residuei334Phosphoserine; by RPS6KA1By similarity1

Post-translational modificationi

Phosphorylated. 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 (By similarity). Phosphorylated by protein kinase AKT1 at Ser-92 (PubMed:15538381).By similarity1 Publication
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

PRIDEiP17431.

PTM databases

iPTMnetiP17431.
PhosphoSitePlusiP17431.

Expressioni

Gene expression databases

GenevisibleiP17431. RN.

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. Interacts (via phosphorylated form) with YWHAZ; this interaction occurs in a p38 MAPK- and AKT-signaling pathways.By similarity

GO - Molecular functioni

Protein-protein interaction databases

MINTiMINT-1210346.

Structurei

3D structure databases

ProteinModelPortaliP17431.
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

Sequence similaritiesi

Contains 2 C3H1-type zinc fingers.PROSITE-ProRule annotation

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

GeneTreeiENSGT00530000063262.
HOGENOMiHOG000233479.
HOVERGENiHBG008483.
InParanoidiP17431.
KOiK18753.
OMAiLQHSYSF.
OrthoDBiEOG091G0957.
PhylomeDBiP17431.

Family and domain databases

Gene3Di4.10.1000.10. 2 hits.
InterProiIPR007635. Tis11B_N.
IPR000571. Znf_CCCH.
[Graphical view]
PfamiPF04553. Tis11B_N. 1 hit.
PF00642. zf-CCCH. 2 hits.
[Graphical view]
SMARTiSM00356. ZnF_C3H1. 2 hits.
[Graphical view]
SUPFAMiSSF90229. SSF90229. 2 hits.
PROSITEiPS50103. ZF_C3H1. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P17431-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTTLVSATI FDLSEVLCKG NKMLNYSTPS AGGCLLDRKA VGTPAGGGFP
60 70 80 90 100
RRHSVTLPSS KFHQNQLLSS LKGEPAPTLS 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):36,399
Last modified:August 1, 1990 - v1
Checksum:iA1547C8BF566196C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52590 mRNA. Translation: CAA36826.1.
X86571 Genomic DNA. Translation: CAA60379.1.
PIRiS10471.
RefSeqiNP_058868.1. NM_017172.1.
UniGeneiRn.6142.

Genome annotation databases

EnsembliENSRNOT00000083677; ENSRNOP00000075412; ENSRNOG00000058646.
GeneIDi29344.
KEGGirno:29344.
UCSCiRGD:62009. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52590 mRNA. Translation: CAA36826.1.
X86571 Genomic DNA. Translation: CAA60379.1.
PIRiS10471.
RefSeqiNP_058868.1. NM_017172.1.
UniGeneiRn.6142.

3D structure databases

ProteinModelPortaliP17431.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-1210346.

PTM databases

iPTMnetiP17431.
PhosphoSitePlusiP17431.

Proteomic databases

PRIDEiP17431.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000083677; ENSRNOP00000075412; ENSRNOG00000058646.
GeneIDi29344.
KEGGirno:29344.
UCSCiRGD:62009. rat.

Organism-specific databases

CTDi677.
RGDi62009. Zfp36l1.

Phylogenomic databases

GeneTreeiENSGT00530000063262.
HOGENOMiHOG000233479.
HOVERGENiHBG008483.
InParanoidiP17431.
KOiK18753.
OMAiLQHSYSF.
OrthoDBiEOG091G0957.
PhylomeDBiP17431.

Enzyme and pathway databases

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

Miscellaneous databases

PROiP17431.

Gene expression databases

GenevisibleiP17431. RN.

Family and domain databases

Gene3Di4.10.1000.10. 2 hits.
InterProiIPR007635. Tis11B_N.
IPR000571. Znf_CCCH.
[Graphical view]
PfamiPF04553. Tis11B_N. 1 hit.
PF00642. zf-CCCH. 2 hits.
[Graphical view]
SMARTiSM00356. ZnF_C3H1. 2 hits.
[Graphical view]
SUPFAMiSSF90229. SSF90229. 2 hits.
PROSITEiPS50103. ZF_C3H1. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTISB_RAT
AccessioniPrimary (citable) accession number: P17431
Secondary accession number(s): Q6LAU8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: November 30, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.