P47974 · TISD_HUMAN
- ProteinmRNA decay activator protein ZFP36L2
- GeneZFP36L2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids494 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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:14981510, PubMed:25106868, PubMed:34611029).
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:14981510, PubMed:20506496, PubMed:25106868).
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
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:14981510, PubMed:20506496, PubMed:25106868).
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
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namemRNA decay activator protein ZFP36L2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP47974
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Involvement in disease
Oocyte/zygote/embryo maturation arrest 13 (OZEMA13)
- Note
- DescriptionAn autosomal recessive female infertility disorder characterized by embryonic development arrest and embryo implantation failure.
- See alsoMIM:620154
Natural variants in OZEMA13
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_087929 | 308 | S>A | in OZEMA13; uncertain significance; dbSNP:rs373995498 | |
VAR_087928 | 308-310 | missing | in OZEMA13; results in decreased mRNA catabolic process |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 157 | Impaired mRNA-binding; when associated with K-195. | ||||
Sequence: E → R | ||||||
Mutagenesis | 195 | Impaired mRNA-binding; when associated with R-157. | ||||
Sequence: E → K | ||||||
Natural variant | VAR_087929 | 308 | in OZEMA13; uncertain significance; dbSNP:rs373995498 | |||
Sequence: S → A | ||||||
Natural variant | VAR_087928 | 308-310 | in OZEMA13; results in decreased mRNA catabolic process | |||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 922 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000089170 | 1-494 | UniProt | mRNA decay activator protein ZFP36L2 | |||
Sequence: MSTTLLSAFYDVDFLCKTEKSLANLNLNNMLDKKAVGTPVAAAPSSGFAPGFLRRHSASNLHALAHPAPSPGSCSPKFPGAANGSSCGSAAAGGPTSYGTLKEPSGGGGTALLNKENKFRDRSFSENGDRSQHLLHLQQQQKGGGGSQINSTRYKTELCRPFEESGTCKYGEKCQFAHGFHELRSLTRHPKYKTELCRTFHTIGFCPYGPRCHFIHNADERRPAPSGGASGDLRAFGTRDALHLGFPREPRPKLHHSLSFSGFPSGHHQPPGGLESPLLLDSPTSRTPPPPSCSSASSCSSSASSCSSASAASTPSGAPTCCASAAAAAAAALLYGTGGAEDLLAPGAPCAACSSASCANNAFAFGPELSSLITPLAIQTHNFAAVAAAAYYRSQQQQQQQGLAPPAQPPAPPSATLPAGAAAPPSPPFSFQLPRRLSDSPVFDAPPSPPDSLSDRDSYLSGSLSSGSLSGSESPSLDPGRRLPIFSRLSISDD | |||||||
Modified residue (large scale data) | 38 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 57 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 57 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 59 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 70 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 73 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 75 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 123 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 125 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 125 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 238 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 257 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 276 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 282 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 426 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 438 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 440 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 448 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 452 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 474 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 487 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 490 | UniProt | Phosphoserine; by RPS6KA1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 490 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 492 | UniProt | Phosphoserine; by RPS6KA1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 492 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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).
Phosphorylation occurs during early preadipocyte differentiation (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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 oocytes (PubMed:34611029).
Expressed in epidermal keratinocytes (at protein level) (PubMed:27182009).
Expressed in oocytes (PubMed:34611029).
Induction
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).
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).
Gene expression databases
Organism-specific databases
Interaction
Subunit
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).
Interacts with CNOT6L
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 CNOT6L
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P47974 | SFN P31947 | 4 | EBI-1644149, EBI-476295 | |
BINARY | P47974 | YWHAE P62258 | 5 | EBI-1644149, EBI-356498 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif, zinc finger, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 93-113 | Disordered | ||||
Sequence: GGPTSYGTLKEPSGGGGTALL | ||||||
Motif | 153-158 | RNA-binding | ||||
Sequence: RYKTEL | ||||||
Zinc finger | 153-181 | C3H1-type 1 | ||||
Sequence: RYKTELCRPFEESGTCKYGEKCQFAHGFH | ||||||
Region | 170-211 | RNA-binding | ||||
Sequence: YGEKCQFAHGFHELRSLTRHPKYKTELCRTFHTIGFCPYGPR | ||||||
Zinc finger | 191-219 | C3H1-type 2 | ||||
Sequence: KYKTELCRTFHTIGFCPYGPRCHFIHNAD | ||||||
Region | 257-293 | Disordered | ||||
Sequence: SLSFSGFPSGHHQPPGGLESPLLLDSPTSRTPPPPSC | ||||||
Region | 397-494 | Disordered | ||||
Sequence: QQQQQGLAPPAQPPAPPSATLPAGAAAPPSPPFSFQLPRRLSDSPVFDAPPSPPDSLSDRDSYLSGSLSSGSLSGSESPSLDPGRRLPIFSRLSISDD | ||||||
Compositional bias | 405-431 | Pro residues | ||||
Sequence: PPAQPPAPPSATLPAGAAAPPSPPFSF | ||||||
Compositional bias | 454-475 | Polar residues | ||||
Sequence: SDRDSYLSGSLSSGSLSGSESP |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length494
- Mass (Da)51,063
- Last updated2007-05-01 v3
- Checksum10E23FA9E2DDABD4
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 96-97 | in Ref. 1; AAA91778 | ||||
Sequence: TS → DL | ||||||
Sequence conflict | 318 | in Ref. 2; CAA55592 | ||||
Sequence: A → T | ||||||
Sequence conflict | 329-332 | in Ref. 2; CAA55592 | ||||
Sequence: AAAA → LR | ||||||
Sequence conflict | 331-332 | in Ref. 1; AAA91778 | ||||
Sequence: Missing | ||||||
Sequence conflict | 400 | in Ref. 5; AAH05010 | ||||
Sequence: Q → QQQQ | ||||||
Compositional bias | 405-431 | Pro residues | ||||
Sequence: PPAQPPAPPSATLPAGAAAPPSPPFSF | ||||||
Sequence conflict | 453-462 | in Ref. 1; AAA91778 | ||||
Sequence: Missing | ||||||
Compositional bias | 454-475 | Polar residues | ||||
Sequence: SDRDSYLSGSLSSGSLSGSESP |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U07802 EMBL· GenBank· DDBJ | AAA91778.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X78992 EMBL· GenBank· DDBJ | CAA55592.1 EMBL· GenBank· DDBJ | mRNA | ||
AC010883 EMBL· GenBank· DDBJ | AAY14992.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00306.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC005010 EMBL· GenBank· DDBJ | AAH05010.1 EMBL· GenBank· DDBJ | mRNA |