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Protein

mRNA decay activator protein ZFP36L2

Gene

ZFP36L2

Organism
Homo sapiens (Human)
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:25106868, PubMed:14981510). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:25106868). 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 (PubMed:25106868). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:20506496, PubMed:25106868, PubMed:14981510). 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 (PubMed:25106868). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). Plays a role in mature peripheral neuron integrity by promoting ARE-containing mRNA decay of the transcriptional repressor REST mRNA. Plays a role in ovulation and oocyte meiotic maturation by promoting ARE-mediated mRNA decay of the luteinizing hormone receptor LHCGR mRNA. 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. 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. 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.By similarity3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri153 – 181C3H1-type 1PROSITE-ProRule annotationAdd BLAST29
Zinc fingeri191 – 219C3H1-type 2PROSITE-ProRule annotationAdd BLAST29

GO - Molecular functioni

  • AU-rich element binding Source: UniProtKB
  • 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
  • poly(A) RNA binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Ribonucleoprotein

Keywords - Ligandi

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000152518-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
mRNA decay activator protein ZFP36L2Curated
Alternative name(s):
Butyrate response factor 21 Publication
EGF-response factor 21 Publication
Short name:
ERF-21 Publication
TPA-induced sequence 11d1 Publication
Zinc finger protein 36, C3H1 type-like 2Imported
Short name:
ZFP36-like 2Imported
Gene namesi
Name:ZFP36L2Imported
Synonyms:BRF2, ERF21 Publication, RNF162C, TIS11D1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:1108. ZFP36L2.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

  • Note: Shuttles between the nucleus and the cytoplasm in a XPO1/CRM1-dependent manner.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in ZFP36L2 may be a cause of leukemias. Frameshfits mutations disrupting ZFP36L2 have been found in a patient with acute myeloid leukemia (PubMed:21109922).

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi157E → R: Impaired mRNA-binding; when associated with K-195. 1 Publication1
Mutagenesisi195E → K: Impaired mRNA-binding; when associated with R-157. 1 Publication1

Organism-specific databases

DisGeNETi678.
OpenTargetsiENSG00000152518.
PharmGKBiPA35028.

Polymorphism and mutation databases

BioMutaiZFP36L2.
DMDMi146291085.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000891701 – 494mRNA decay activator protein ZFP36L2Add BLAST494

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei57PhosphoserineCombined sources1
Modified residuei125PhosphoserineCombined sources1
Modified residuei238PhosphothreonineCombined sources1
Modified residuei490Phosphoserine; by RPS6KA11 Publication1
Modified residuei492Phosphoserine; by RPS6KA11 Publication1

Post-translational modificationi

Phosphorylated by RPS6KA1 at Ser-490 and Ser-492 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 (PubMed:25106868). Phosphorylation occurs during early preadipocyte differentiation (By similarity).By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP47974.
MaxQBiP47974.
PaxDbiP47974.
PeptideAtlasiP47974.
PRIDEiP47974.

PTM databases

iPTMnetiP47974.
PhosphoSitePlusiP47974.

Expressioni

Tissue specificityi

Expressed mainly in the basal epidermal layer, weakly in the suprabasal epidermal layers (PubMed:27182009). Expressed in epidermal keratinocytes (at protein level) (PubMed:27182009).1 Publication

Inductioni

Up-regulated by butyrate in colorectal cancer cells (PubMed:10367403). Up-regulated in keratinocytes after wounding (PubMed:20166898, PubMed:27182009). Up-regulated strongly by granulocyte macrophage colony-stimulating factor (GM-CSF) in keratinocytes (PubMed:20166898). Up-regulated moderately by transforming growth factor (TGF-beta), epidermal growth factor (EGF), tumor necrosis factor (TNF-alpha) and fibroblast growth factor (FGF1) in keratinocytes (PubMed:20166898). Up-regulated also by glucocorticoid dexamethasone in keratinocytes (PubMed:20166898).3 Publications

Gene expression databases

BgeeiENSG00000152518.
CleanExiHS_BRF2.
HS_ZFP36L2.
GenevisibleiP47974. HS.

Organism-specific databases

HPAiHPA047428.

Interactioni

Subunit structurei

Associates with the cytoplasmic CCR4-NOT deadenylase to trigger ARE-containing mRNA deadenylation and decay processes (PubMed:25106868). Interacts with CNOT7; this interaction is inhibited in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner (PubMed:25106868).1 Publication

Protein-protein interaction databases

BioGridi107145. 8 interactors.
IntActiP47974. 8 interactors.
STRINGi9606.ENSP00000282388.

Structurei

Secondary structure

1494
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni152 – 155Combined sources4
Beta strandi156 – 158Combined sources3
Helixi160 – 165Combined sources6
Helixi171 – 173Combined sources3
Beta strandi175 – 179Combined sources5
Helixi180 – 182Combined sources3
Turni190 – 193Combined sources4
Helixi198 – 203Combined sources6
Helixi209 – 211Combined sources3
Beta strandi213 – 215Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RGONMR-A151-220[»]
ProteinModelPortaliP47974.
SMRiP47974.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP47974.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni170 – 211RNA-binding2 PublicationsAdd BLAST42

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi153 – 158RNA-binding2 Publications6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi106 – 109Poly-Gly4
Compositional biasi138 – 141Poly-Gln4
Compositional biasi143 – 146Poly-Gly4
Compositional biasi288 – 291Poly-Pro4
Compositional biasi323 – 332Poly-Ala10
Compositional biasi384 – 390Poly-Ala7
Compositional biasi395 – 401Poly-Gln7

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri153 – 181C3H1-type 1PROSITE-ProRule annotationAdd BLAST29
Zinc fingeri191 – 219C3H1-type 2PROSITE-ProRule annotationAdd BLAST29

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1677. Eukaryota.
COG5063. LUCA.
GeneTreeiENSGT00530000063262.
HOGENOMiHOG000233479.
HOVERGENiHBG008483.
InParanoidiP47974.
KOiK18753.
OMAiQRDRPKL.
OrthoDBiEOG091G0957.
PhylomeDBiP47974.
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.

P47974-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTTLLSAFY DVDFLCKTEK SLANLNLNNM LDKKAVGTPV AAAPSSGFAP
60 70 80 90 100
GFLRRHSASN LHALAHPAPS PGSCSPKFPG AANGSSCGSA AAGGPTSYGT
110 120 130 140 150
LKEPSGGGGT ALLNKENKFR DRSFSENGDR SQHLLHLQQQ QKGGGGSQIN
160 170 180 190 200
STRYKTELCR PFEESGTCKY GEKCQFAHGF HELRSLTRHP KYKTELCRTF
210 220 230 240 250
HTIGFCPYGP RCHFIHNADE RRPAPSGGAS GDLRAFGTRD ALHLGFPREP
260 270 280 290 300
RPKLHHSLSF SGFPSGHHQP PGGLESPLLL DSPTSRTPPP PSCSSASSCS
310 320 330 340 350
SSASSCSSAS AASTPSGAPT CCASAAAAAA AALLYGTGGA EDLLAPGAPC
360 370 380 390 400
AACSSASCAN NAFAFGPELS SLITPLAIQT HNFAAVAAAA YYRSQQQQQQ
410 420 430 440 450
QGLAPPAQPP APPSATLPAG AAAPPSPPFS FQLPRRLSDS PVFDAPPSPP
460 470 480 490
DSLSDRDSYL SGSLSSGSLS GSESPSLDPG RRLPIFSRLS ISDD
Length:494
Mass (Da):51,063
Last modified:May 1, 2007 - v3
Checksum:i10E23FA9E2DDABD4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti96 – 97TS → DL in AAA91778 (PubMed:8545129).Curated2
Sequence conflicti318A → T in CAA55592 (PubMed:7835719).Curated1
Sequence conflicti329 – 332AAAA → LR in CAA55592 (PubMed:7835719).Curated4
Sequence conflicti331 – 332Missing in AAA91778 (PubMed:8545129).Curated2
Sequence conflicti400Q → QQQQ in AAH05010 (PubMed:15489334).Curated1
Sequence conflicti453 – 462Missing in AAA91778 (PubMed:8545129).Curated10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07802 Genomic DNA. Translation: AAA91778.1.
X78992 mRNA. Translation: CAA55592.1.
AC010883 Genomic DNA. Translation: AAY14992.1.
CH471053 Genomic DNA. Translation: EAX00306.1.
BC005010 mRNA. Translation: AAH05010.1.
CCDSiCCDS1811.1.
PIRiS49147.
RefSeqiNP_008818.3. NM_006887.4.
UniGeneiHs.503093.

Genome annotation databases

EnsembliENST00000282388; ENSP00000282388; ENSG00000152518.
GeneIDi678.
KEGGihsa:678.
UCSCiuc002rsv.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07802 Genomic DNA. Translation: AAA91778.1.
X78992 mRNA. Translation: CAA55592.1.
AC010883 Genomic DNA. Translation: AAY14992.1.
CH471053 Genomic DNA. Translation: EAX00306.1.
BC005010 mRNA. Translation: AAH05010.1.
CCDSiCCDS1811.1.
PIRiS49147.
RefSeqiNP_008818.3. NM_006887.4.
UniGeneiHs.503093.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RGONMR-A151-220[»]
ProteinModelPortaliP47974.
SMRiP47974.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107145. 8 interactors.
IntActiP47974. 8 interactors.
STRINGi9606.ENSP00000282388.

PTM databases

iPTMnetiP47974.
PhosphoSitePlusiP47974.

Polymorphism and mutation databases

BioMutaiZFP36L2.
DMDMi146291085.

Proteomic databases

EPDiP47974.
MaxQBiP47974.
PaxDbiP47974.
PeptideAtlasiP47974.
PRIDEiP47974.

Protocols and materials databases

DNASUi678.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282388; ENSP00000282388; ENSG00000152518.
GeneIDi678.
KEGGihsa:678.
UCSCiuc002rsv.5. human.

Organism-specific databases

CTDi678.
DisGeNETi678.
GeneCardsiZFP36L2.
HGNCiHGNC:1108. ZFP36L2.
HPAiHPA047428.
MIMi612053. gene.
neXtProtiNX_P47974.
OpenTargetsiENSG00000152518.
PharmGKBiPA35028.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1677. Eukaryota.
COG5063. LUCA.
GeneTreeiENSGT00530000063262.
HOGENOMiHOG000233479.
HOVERGENiHBG008483.
InParanoidiP47974.
KOiK18753.
OMAiQRDRPKL.
OrthoDBiEOG091G0957.
PhylomeDBiP47974.
TreeFamiTF315463.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000152518-MONOMER.

Miscellaneous databases

ChiTaRSiZFP36L2. human.
EvolutionaryTraceiP47974.
GenomeRNAii678.
PROiP47974.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000152518.
CleanExiHS_BRF2.
HS_ZFP36L2.
GenevisibleiP47974. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P47974
Secondary accession number(s): Q53TB4, Q9BSJ3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 1, 2007
Last modified: November 30, 2016
This is version 157 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.