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Protein

mRNA decay activator protein ZFP36L2

Gene

Zfp36l2

Organism
Mus musculus (Mouse)
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:22701344, PubMed:22367205, PubMed:25505318, PubMed:24830504, 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 deadenylase complex and probably other 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). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:22701344, PubMed:22367205, PubMed:25505318, PubMed:24830504). Promotes ARE-containing mRNA decay of the low-density lipoprotein (LDL) receptor (LDLR) mRNA in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner (By similarity). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (PubMed:22701344). Plays a role in mature peripheral neuron integrity by promoting ARE-containing mRNA decay of the transcriptional repressor REST mRNA (PubMed:25505318). Plays a role in ovulation and oocyte meiotic maturation by promoting ARE-mediated mRNA decay of the luteinizing hormone receptor LHCGR mRNA (PubMed:24830504). Acts as a negative regulator of erythroid cell differentiation: promotes glucocorticoid-induced self-renewal of erythroid cells by binding mRNAs that are induced or highly expressed during terminal erythroid differentiation and promotes their degradation, preventing erythroid cell differentiation (PubMed:19633199, PubMed:23748442). In association with ZFP36L1 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 process and functional immune cell formation (PubMed:27102483). Together with ZFP36L1 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).By similarity8 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri155 – 183C3H1-type 1PROSITE-ProRule annotationAdd BLAST29
Zinc fingeri193 – 221C3H1-type 2PROSITE-ProRule annotationAdd BLAST29

GO - Molecular functioni

GO - Biological processi

  • 3'-UTR-mediated mRNA destabilization Source: UniProtKB
  • cellular response to epidermal growth factor stimulus Source: UniProtKB
  • cellular response to fibroblast growth factor stimulus Source: UniProtKB
  • cellular response to glucocorticoid stimulus Source: UniProtKB
  • cellular response to granulocyte macrophage colony-stimulating factor stimulus Source: UniProtKB
  • cellular response to phorbol 13-acetate 12-myristate Source: UniProtKB
  • cellular response to transforming growth factor beta stimulus Source: UniProtKB
  • cellular response to tumor necrosis factor Source: UniProtKB
  • definitive hemopoiesis Source: UniProtKB
  • ERK1 and ERK2 cascade Source: UniProtKB
  • hemopoiesis Source: UniProtKB
  • MAPK cascade Source: UniProtKB
  • mRNA catabolic process Source: UniProtKB
  • negative regulation of fat cell differentiation Source: UniProtKB
  • negative regulation of mitotic cell cycle phase transition Source: UniProtKB
  • negative regulation of stem cell differentiation Source: UniProtKB
  • nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: MGI
  • positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: UniProtKB
  • regulation of B cell differentiation Source: UniProtKB
  • regulation of mRNA stability Source: UniProtKB
  • response to wounding Source: UniProtKB
  • somatic stem cell division Source: UniProtKB
  • somatic stem cell population maintenance Source: UniProtKB
  • T cell differentiation in thymus Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Ribonucleoprotein

Keywords - Ligandi

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

Names & Taxonomyi

Protein namesi
Recommended name:
mRNA decay activator protein ZFP36L2Curated
Alternative name(s):
Butyrate response factor 2By similarity
TPA-induced sequence 11d1 Publication
Zinc finger protein 36, C3H1 type-like 2Imported
Short name:
ZFP36-like 2Imported
Gene namesi
Name:Zfp36l2Imported
Synonyms:Brf2, Tis11d1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:107945. Zfp36l2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: GO_Central
  • intracellular ribonucleoprotein complex Source: UniProtKB-KW
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Lethality between 2 weeks of birth, due to pancytopenia (PubMed:19633199). Peripheral blood shows a decrease in red and white cells, hemoglobin, hematocrit and platelets (PubMed:19633199). Yolk sacs from embryonic day 11.5 (E11.5) and fetal livers from E14.5 display markedly reduced numbers of definitive multilineage and lineage-committed hematopoietic progenitors (PubMed:19633199). Mice lacking the N-terminus (DeltaN-ZFP36L2) display female infertility, with embryos that cannot progress beyond the 2-cell stage of development (PubMed:15342461). Show evidence of axonal and fiber degeneration (PubMed:25505318). Exhibit increased REST mRNA stability and REST protein expression in primary neuronal cells from superior cervical ganglion (SCG) and dorsal root ganglion (DRG) (PubMed:25505318). Mice lacking both ZFP36L2 and ZFP36L1 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 mRNA and protein in thymocytes (PubMed:20622884). Conditional knockout mice of both ZFP36L2 and ZFP36L1 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).5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi176C → S: Inhibits RNA-binding. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000891711 – 484mRNA decay activator protein ZFP36L2Add BLAST484

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei57PhosphoserineBy similarity1
Modified residuei127PhosphoserineBy similarity1
Modified residuei480Phosphoserine; by RPS6KA1By similarity1
Modified residuei482Phosphoserine; by RPS6KA1By similarity1

Post-translational modificationi

Phosphorylated by RPS6KA1 at Ser-480 and Ser-482 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 (LDL) receptor (LDLR) mRNA (By similarity). Phosphorylation occurs during early preadipocyte differentiation (PubMed:22701344).By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP23949.
MaxQBiP23949.
PaxDbiP23949.
PeptideAtlasiP23949.
PRIDEiP23949.

PTM databases

iPTMnetiP23949.
PhosphoSitePlusiP23949.

Expressioni

Tissue specificityi

Expressed in preadipocytes and adipocytes (at protein level) (PubMed:22701344). Expressed at highest level in lymphoid tissues such as thymus, spleen, lung, uterus, ovary, small and large intestine, mammary gland, fat and bone marrow (PubMed:19633199, PubMed:22367205). Expressed at intermediate level in kidney, heart, adrenal, eye and fetal liver (PubMed:19633199). Weakly expressed in brain, skeletal muscle and liver (PubMed:19633199, PubMed:22367205). Expressed through B lymphocyte development (PubMed:27102483). Expressed in superior cervical ganglion (SCG) and dorsal root ganglion (DRG) (PubMed:25505318). Expressed in embryonic stem cells (ESCs) (PubMed:24733888).6 Publications

Developmental stagei

In embryos, expression is detected at E7, increases at E9.5, and then remains constant through E18.5 (PubMed:19633199). Expression in the yolk sac is relatively constant between E10.5 and E18.5 (PubMed:19633199). Placenta expression is also constant throughout development with a slight decrease observed at E18.5 (PubMed:19633199). Expressed in burst-forming unit-erythroid (BFU-E) progenitor cells and down-regulated as erythroid cells differentiate (PubMed:23748442).2 Publications

Inductioni

Up-regulated in response to fibroblast growth factor FGF4 in embryonic stem cells (ESCs) in a p38 MAPK-dependent manner (at protein level) (PubMed:24733888). Up-regulated by glucocorticoid agonists, such as dexamethasone (DEX), in burst-forming unit-erythroid (BFU-E) progenitors in a receptor NR3C1-dependent manner (PubMed:23748442). Down-regulated during erythroid cell differentiation (PubMed:23748442). Down-regulated during the conversion from quiescence to activated satellite cells upon muscle injury (PubMed:23046558, PubMed:25815583).4 Publications

Gene expression databases

BgeeiENSMUSG00000045817.
CleanExiMM_ZFP36L2.
GenevisibleiP23949. MM.

Interactioni

Subunit structurei

Associates with the cytoplasmic CCR4-NOT deadenylase to trigger ARE-containing mRNA deadenylation and decay processes. Interacts with CNOT7; this interaction is inhibited in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner.By similarity

Protein-protein interaction databases

IntActiP23949. 3 interactors.
MINTiMINT-4137984.
STRINGi10090.ENSMUSP00000050820.

Structurei

3D structure databases

ProteinModelPortaliP23949.
SMRiP23949.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni172 – 213RNA-bindingBy similarityAdd BLAST42

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi155 – 160RNA-bindingBy similarity6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi93 – 96Poly-Gly4
Compositional biasi140 – 143Poly-Gln4
Compositional biasi229 – 232Poly-Gly4
Compositional biasi292 – 295Poly-Pro4
Compositional biasi296 – 319Ser-richAdd BLAST24
Compositional biasi326 – 332Poly-Ala7
Compositional biasi383 – 389Poly-Ala7
Compositional biasi401 – 440Pro-richAdd BLAST40

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri155 – 183C3H1-type 1PROSITE-ProRule annotationAdd BLAST29
Zinc fingeri193 – 221C3H1-type 2PROSITE-ProRule annotationAdd BLAST29

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1677. Eukaryota.
COG5063. LUCA.
GeneTreeiENSGT00530000063262.
HOGENOMiHOG000233479.
HOVERGENiHBG008483.
InParanoidiP23949.
KOiK18753.
OMAiQRDRPKL.
OrthoDBiEOG091G0957.
TreeFamiTF315463.

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.

P23949-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTTLLSPFY DIDFLCKTEK SLANLNLNNM LDKKAVGTPV AAAPSSSFTP
60 70 80 90 100
GFLRRHSASN LHALAHPVPS PGSCSPKFPG APNGGGSSCG PAGGGGLASY
110 120 130 140 150
GQLKEPSGGS GTALVTKESK FRDRSFSENG ERSQHLLHLQ QQQKGGSGSQ
160 170 180 190 200
INSTRYKTEL CRPFEESGTC KYGEKCQFAH GFHELRSLTR HPKYKTELCR
210 220 230 240 250
TFHTIGFCPY GPRCHFIHNA DERRPAPSGG GGASGDLRAF GARDALHLGF
260 270 280 290 300
AREPRPKLHH SLSFSGFPSG HHQPPGGLES PLLLDSPTSR TPPPPSSSAS
310 320 330 340 350
SCSSSASSCS SASAASTPSG APTCCATAAA AALLYGPGGA EDLLSPGAPC
360 370 380 390 400
ASCSSSGANN AFAFGPELSS LITPLAIQTH NFAAAAAAAY YRNQQQGLTG
410 420 430 440 450
PAPPPAQPPA APAPPSPPFG FQLPRRLSES PVFDAPPSPP DSLSDRDSYL
460 470 480
SGSLSSGSLS GSESPSLDPG RRLPIFSRLS ISDD
Length:484
Mass (Da):50,070
Last modified:September 18, 2013 - v2
Checksum:iFBEB18B64775842A
GO

Sequence cautioni

The sequence AAA39709 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence AAA72946 differs from that shown. Reason: Frameshift at position 385.Curated
The sequence AAA72946 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti413A → T in BAE42014 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK160955 mRNA. Translation: BAE36112.1.
AK170763 mRNA. Translation: BAE42014.1.
AC132455 Genomic DNA. No translation available.
BC139416 mRNA. Translation: AAI39417.1.
M97165 Genomic DNA. Translation: AAA39709.1. Sequence problems.
M58564 mRNA. Translation: AAA72946.1. Sequence problems.
CCDSiCCDS28998.1.
PIRiC39590.
RefSeqiNP_001001806.1. NM_001001806.2.
UniGeneiMm.259321.

Genome annotation databases

EnsembliENSMUST00000060366; ENSMUSP00000050820; ENSMUSG00000045817.
GeneIDi12193.
KEGGimmu:12193.
UCSCiuc008dsq.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK160955 mRNA. Translation: BAE36112.1.
AK170763 mRNA. Translation: BAE42014.1.
AC132455 Genomic DNA. No translation available.
BC139416 mRNA. Translation: AAI39417.1.
M97165 Genomic DNA. Translation: AAA39709.1. Sequence problems.
M58564 mRNA. Translation: AAA72946.1. Sequence problems.
CCDSiCCDS28998.1.
PIRiC39590.
RefSeqiNP_001001806.1. NM_001001806.2.
UniGeneiMm.259321.

3D structure databases

ProteinModelPortaliP23949.
SMRiP23949.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP23949. 3 interactors.
MINTiMINT-4137984.
STRINGi10090.ENSMUSP00000050820.

PTM databases

iPTMnetiP23949.
PhosphoSitePlusiP23949.

Proteomic databases

EPDiP23949.
MaxQBiP23949.
PaxDbiP23949.
PeptideAtlasiP23949.
PRIDEiP23949.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000060366; ENSMUSP00000050820; ENSMUSG00000045817.
GeneIDi12193.
KEGGimmu:12193.
UCSCiuc008dsq.2. mouse.

Organism-specific databases

CTDi678.
MGIiMGI:107945. Zfp36l2.

Phylogenomic databases

eggNOGiKOG1677. Eukaryota.
COG5063. LUCA.
GeneTreeiENSGT00530000063262.
HOGENOMiHOG000233479.
HOVERGENiHBG008483.
InParanoidiP23949.
KOiK18753.
OMAiQRDRPKL.
OrthoDBiEOG091G0957.
TreeFamiTF315463.

Miscellaneous databases

ChiTaRSiZfp36l2. mouse.
PROiP23949.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000045817.
CleanExiMM_ZFP36L2.
GenevisibleiP23949. MM.

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 nameiTISD_MOUSE
AccessioniPrimary (citable) accession number: P23949
Secondary accession number(s): B9EIF6, Q3TCE3, Q3TU59
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: September 18, 2013
Last modified: November 30, 2016
This is version 120 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.