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Protein

mRNA decay activator protein ZFP36L2

Gene

ZFP36L2

Organism
Homo sapiens (Human)
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: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
  • DNA-binding transcription factor activity Source: ProtInc
  • DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
  • metal ion binding Source: UniProtKB-KW
  • mRNA 3'-UTR AU-rich region binding Source: UniProtKB
  • mRNA 3'-UTR binding Source: GO_Central
  • RNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, DNA-binding, Ribonucleoprotein, RNA-binding
LigandMetal-binding, Zinc

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

EuPathDBiHostDB:ENSG00000152518.6
HGNCiHGNC:1108 ZFP36L2
MIMi612053 gene
neXtProtiNX_P47974

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

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).1 Publication

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
ProteomicsDBi55827

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 Expressed in 243 organ(s), highest expression level in endometrium
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, 9 interactors
IntActiP47974, 8 interactors
STRINGi9606.ENSP00000282388

Structurei

Secondary structure

1494
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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
OMAiYGPLKEP
OrthoDBiEOG091G0957
PhylomeDBiP47974
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

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

Similar proteinsi

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, 9 interactors
IntActiP47974, 8 interactors
STRINGi9606.ENSP00000282388

PTM databases

iPTMnetiP47974
PhosphoSitePlusiP47974

Polymorphism and mutation databases

BioMutaiZFP36L2
DMDMi146291085

Proteomic databases

EPDiP47974
MaxQBiP47974
PaxDbiP47974
PeptideAtlasiP47974
PRIDEiP47974
ProteomicsDBi55827

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
EuPathDBiHostDB:ENSG00000152518.6
GeneCardsiZFP36L2
HGNCiHGNC:1108 ZFP36L2
HPAiHPA047428
MIMi612053 gene
neXtProtiNX_P47974
OpenTargetsiENSG00000152518
PharmGKBiPA35028
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

ChiTaRSiZFP36L2 human
EvolutionaryTraceiP47974
GenomeRNAii678
PROiPR:P47974
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000152518 Expressed in 243 organ(s), highest expression level in endometrium
CleanExiHS_BRF2
HS_ZFP36L2
GenevisibleiP47974 HS

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 nameiTISD_HUMAN
AccessioniPrimary (citable) accession number: P47974
Secondary accession number(s): Q53TB4, Q9BSJ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 1, 2007
Last modified: November 7, 2018
This is version 172 of the entry and version 3 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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