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Protein

mRNA decay activator protein ZFP36L1

Gene

ZFP36L1

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:12198173, PubMed:15538381, PubMed:15467755, PubMed:17030608, PubMed:19179481, PubMed:20702587, PubMed:24700863, PubMed:25106868, PubMed:25014217, PubMed:26542173). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:15687258). 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:15687258, PubMed:18326031, PubMed:25106868). 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:12198173, PubMed:15538381, PubMed:15467755, PubMed:17030608, PubMed:19179481, PubMed:20702587, PubMed:24700863, PubMed:25106868, PubMed:25014217, PubMed:26542173). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (By similarity). 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 (PubMed:20702587). Positively regulates monocyte/macrophage cell differentiation by promoting ARE-mediated mRNA decay of the cyclin-dependent kinase CDK6 mRNA (PubMed:26542173). 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 (By similarity). May play a role in mediating pro-apoptotic effects in malignant B-cells by promoting ARE-mediated mRNA decay of BCL2 mRNA (PubMed:25014217). 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 (By similarity). 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 (By similarity). Participates in the delivery of target ARE-mRNAs to processing bodies (PBs) (PubMed:17369404). 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 (PubMed:21832157). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (PubMed:15967811). Plays a role in vasculogenesis and endocardial development (By similarity). Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis (PubMed:27182009). Plays a role in myoblast cell differentiation (By similarity).By similarity16 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

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-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
SIGNORiQ07352

Names & Taxonomyi

Protein namesi
Recommended name:
mRNA decay activator protein ZFP36L1Curated
Alternative name(s):
Butyrate response factor 12 Publications
EGF-response factor 11 Publication
Short name:
ERF-11 Publication
TPA-induced sequence 11bBy similarity
Zinc finger protein 36, C3H1 type-like 1Imported
Short name:
ZFP36-like 1Imported
Gene namesi
Name:ZFP36L1Imported
Synonyms:BERG361 Publication, BRF12 Publications, ERF11 Publication, RNF162B, TIS11BBy similarity
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000185650.9
HGNCiHGNC:1107 ZFP36L1
MIMi601064 gene
neXtProtiNX_Q07352

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi54S → A: Inhibits MAPKAPK2-mediated ARE-containing mRNA stabilization; when associated with A-92 and A-203. 1 Publication1
Mutagenesisi90S → A: Inhibits interaction with 14-3-3 proteins and AKT1-mediated ARE-containing mRNA stabilization, but does not affect ARE binding; when associated with A-92. 1 Publication1
Mutagenesisi92S → A: Inhibits MAPKAPK2-mediated ARE-containing mRNA stabilization; when associated with A-54 and A-203. Inhibits interaction with 14-3-3 proteins and AKT1-mediated ARE-containing mRNA stabilization; when associated with A-203. Inhibits interaction with 14-3-3 proteins and AKT1-mediated ARE-containing mRNA stabilization, but does not affect ARE binding; when associated with A-90. 3 Publications1
Mutagenesisi120C → R: Reduces binding to ARE-containing mRNAs and ARE-mediated mRNA decay. Inhibits binding to ARE-containing mRNAs and ARE-mediated mRNA decay; when associated with R-158. 2 Publications1
Mutagenesisi158C → R: Reduces binding to ARE-containing mRNAs and ARE-mediated mRNA decay. Inhibits binding to ARE-containing mRNAs and ARE-mediated mRNA decay; when associated with R-120. 2 Publications1
Mutagenesisi203S → A: Inhibits interaction with 14-3-3 proteins and AKT1-mediated ARE-containing mRNA stabilization; when associated with A-92. Inhibits MAPKAPK2-mediated ARE-containing mRNA stabilization; when associated with A-54 and A-92. 2 Publications1
Mutagenesisi334S → A: Inhibits p38 MAPK-mediated LDLR mRNA stabilization, but does not inhibit interaction with CNOT1 and CNOT7; when associated with A-336. 1 Publication1
Mutagenesisi336S → A: Inhibits p38 MAPK-mediated LDLR mRNA stabilization, but does not inhibit interaction with CNOT1 and CNOT7; when associated with A-334. 1 Publication1

Organism-specific databases

DisGeNETi677
OpenTargetsiENSG00000185650
PharmGKBiPA35027

Polymorphism and mutation databases

BioMutaiZFP36L1
DMDMi1351254

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000891671 – 338mRNA decay activator protein ZFP36L1Add BLAST338

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei54Phosphoserine; by MAPKAPK2Combined sources1 Publication1
Modified residuei90Phosphoserine; by PKB/AKT11 Publication1
Modified residuei92Phosphoserine; by PKB/AKT1 and MAPKAPK22 Publications1
Modified residuei203Phosphoserine; by PKB/AKT1 and MAPKAPK22 Publications1
Modified residuei318PhosphoserineCombined sources1
Modified residuei334Phosphoserine; by RPS6KA11 Publication1

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 (PubMed:25106868). 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 (PubMed:15538381, PubMed:17030608). AKT1-mediated phosphorylation at Ser-92 does not impair ARE-containing RNA-binding (PubMed:15538381). 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 (PubMed:18326031). MAPKAPK2-mediated phosphorylations at Ser-54, Ser-92 and Ser-203 do not impair ARE-containing RNA-binding (PubMed:18326031). 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).By similarity5 Publications
Ubiquitinated. Ubiquitination leads to proteasomal degradation, a process inhibited by phosphorylations at Ser-90, Ser-92 and Ser-203 (PubMed:17030608).1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ07352
MaxQBiQ07352
PaxDbiQ07352
PeptideAtlasiQ07352
PRIDEiQ07352
ProteomicsDBi58515

PTM databases

iPTMnetiQ07352
PhosphoSitePlusiQ07352

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). Expressed in osteoblasts (PubMed:15465005).2 Publications

Inductioni

Down-regulated under hypoxic conditions in endothelial cells (at protein level) (PubMed:21832157). Up-regulated by growth factor (TGF-beta), cytokines, tumor necrosis factor (TNF-alpha) and epidermal growth factor (EGF) in keratinocytes (PubMed:20166898). Up-regulated also by glucocorticoid dexamethasone in keratinocytes (PubMed:20166898). Up-regulated in keratinocytes in response to wounding in a p38 MAPK-dependent manner (PubMed:20166898, PubMed:27182009). Up-regulated by the parathyroid hormone (PTH) in osteoblast-like cells in a cAMP/PKA-dependent manner (PubMed:15465005, PubMed:19179481). Up-regulated in response to adrenocorticotropic hormone (ACTH) (PubMed:19179481). Up-regulated during monocyte/macrophage differentiation in response to phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (PubMed:26542173). Down-regulated by butyrate in colorectal cancer cells (PubMed:10367403).7 Publications

Gene expression databases

BgeeiENSG00000185650 Expressed in 234 organ(s), highest expression level in oviduct epithelium
CleanExiHS_BRF1
HS_ZFP36L1
ExpressionAtlasiQ07352 baseline and differential
GenevisibleiQ07352 HS

Organism-specific databases

HPAiHPA001301

Interactioni

Subunit structurei

Associates with the cytoplasmic CCR4-NOT deadenylase and RNA exosome complexes to trigger ARE-containing mRNA deadenylation and decay processes (PubMed:15687258, PubMed:18326031, PubMed:25106868). Interacts with CNOT1 (PubMed:25106868). Interacts (via N-terminus) with CNOT6 (PubMed:15687258, PubMed:18326031). 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). Interacts with DCP1A (PubMed:15687258). Interacts (via N-terminus) with DCP2 (PubMed:15687258, PubMed:18326031). Interacts (via N-terminus) with EXOSC2 (PubMed:15687258, PubMed:18326031). Interacts with XRN1 (PubMed:15687258). Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a protein kinase AKT1-dependent manner (PubMed:15538381, PubMed:17030608, PubMed:18326031). Interacts (via phosphorylated form) with YWHAZ; this interaction occurs in a p38 MAPK- and AKT-signaling pathways (By similarity).By similarity16 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAPK14Q165392EBI-721823,EBI-73946

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107144, 15 interactors
IntActiQ07352, 11 interactors
MINTiQ07352
STRINGi9606.ENSP00000337386

Structurei

3D structure databases

ProteinModelPortaliQ07352
SMRiQ07352
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ07352

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 111Necessary and sufficient for the association with mRNA decay enzymes and mRNA decay activation1 PublicationAdd BLAST111
Regioni185 – 338Necessary for mRNA decay activation1 PublicationAdd 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
InParanoidiQ07352
KOiK18753
OMAiLQHSYSF
OrthoDBiEOG091G0957
PhylomeDBiQ07352
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 4 potential isoforms that are computationally mapped.Show allAlign All

Q07352-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTTTLVSATI FDLSEVLCKG NKMLNYSAPS AGGCLLDRKA VGTPAGGGFP
60 70 80 90 100
RRHSVTLPSS KFHQNQLLSS LKGEPAPALS SRDSRFRDRS FSEGGERLLP
110 120 130 140 150
TQKQPGGGQV NSSRYKTELC RPFEENGACK YGDKCQFAHG IHELRSLTRH
160 170 180 190 200
PKYKTELCRT FHTIGFCPYG PRCHFIHNAE ERRALAGARD LSADRPRLQH
210 220 230 240 250
SFSFAGFPSA AATAAATGLL DSPTSITPPP ILSADDLLGS PTLPDGTNNP
260 270 280 290 300
FAFSSQELAS LFAPSMGLPG GGSPTTFLFR PMSESPHMFD SPPSPQDSLS
310 320 330
DQEGYLSSSS SSHSGSDSPT LDNSRRLPIF SRLSISDD
Length:338
Mass (Da):36,314
Last modified:February 1, 1996 - v1
Checksum:i98236CD40C4531D2
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3V2P5G3V2P5_HUMAN
mRNA decay activator protein ZFP36L...
ZFP36L1
207Annotation score:
G3V2D5G3V2D5_HUMAN
mRNA decay activator protein ZFP36L...
ZFP36L1
176Annotation score:
G3V515G3V515_HUMAN
mRNA decay activator protein ZFP36L...
ZFP36L1
189Annotation score:
G3V382G3V382_HUMAN
mRNA decay activator protein ZFP36L...
ZFP36L1
69Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti63H → R in CAA67781 (PubMed:8898945).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X79066, X79067 mRNA Translation: CAA55670.1
X99404 mRNA Translation: CAA67781.1
BT019468 mRNA Translation: AAV38275.1
BC018340 mRNA Translation: AAH18340.1
CCDSiCCDS9791.1
PIRiS34854
RefSeqiNP_001231627.1, NM_001244698.1
NP_001231630.1, NM_001244701.1
NP_004917.2, NM_004926.3
UniGeneiHs.707091
Hs.85155

Genome annotation databases

EnsembliENST00000336440; ENSP00000337386; ENSG00000185650
ENST00000439696; ENSP00000388402; ENSG00000185650
GeneIDi677
KEGGihsa:677
UCSCiuc001xkh.3 human

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X79066, X79067 mRNA Translation: CAA55670.1
X99404 mRNA Translation: CAA67781.1
BT019468 mRNA Translation: AAV38275.1
BC018340 mRNA Translation: AAH18340.1
CCDSiCCDS9791.1
PIRiS34854
RefSeqiNP_001231627.1, NM_001244698.1
NP_001231630.1, NM_001244701.1
NP_004917.2, NM_004926.3
UniGeneiHs.707091
Hs.85155

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1W0VX-ray2.27C325-333[»]
1W0WX-ray2.10C325-333[»]
ProteinModelPortaliQ07352
SMRiQ07352
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107144, 15 interactors
IntActiQ07352, 11 interactors
MINTiQ07352
STRINGi9606.ENSP00000337386

PTM databases

iPTMnetiQ07352
PhosphoSitePlusiQ07352

Polymorphism and mutation databases

BioMutaiZFP36L1
DMDMi1351254

Proteomic databases

EPDiQ07352
MaxQBiQ07352
PaxDbiQ07352
PeptideAtlasiQ07352
PRIDEiQ07352
ProteomicsDBi58515

Protocols and materials databases

DNASUi677
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336440; ENSP00000337386; ENSG00000185650
ENST00000439696; ENSP00000388402; ENSG00000185650
GeneIDi677
KEGGihsa:677
UCSCiuc001xkh.3 human

Organism-specific databases

CTDi677
DisGeNETi677
EuPathDBiHostDB:ENSG00000185650.9
GeneCardsiZFP36L1
HGNCiHGNC:1107 ZFP36L1
HPAiHPA001301
MIMi601064 gene
neXtProtiNX_Q07352
OpenTargetsiENSG00000185650
PharmGKBiPA35027
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1677 Eukaryota
COG5063 LUCA
GeneTreeiENSGT00530000063262
HOGENOMiHOG000233479
HOVERGENiHBG008483
InParanoidiQ07352
KOiK18753
OMAiLQHSYSF
OrthoDBiEOG091G0957
PhylomeDBiQ07352
TreeFamiTF315463

Enzyme and pathway databases

ReactomeiR-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
SIGNORiQ07352

Miscellaneous databases

ChiTaRSiZFP36L1 human
EvolutionaryTraceiQ07352
GeneWikiiZFP36L1
GenomeRNAii677
PROiPR:Q07352
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185650 Expressed in 234 organ(s), highest expression level in oviduct epithelium
CleanExiHS_BRF1
HS_ZFP36L1
ExpressionAtlasiQ07352 baseline and differential
GenevisibleiQ07352 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 nameiTISB_HUMAN
AccessioniPrimary (citable) accession number: Q07352
Secondary accession number(s): Q13851
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: September 12, 2018
This is version 173 of the entry and version 1 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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