Q13542 · 4EBP2_HUMAN
- ProteinEukaryotic translation initiation factor 4E-binding protein 2
- GeneEIF4EBP2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids120 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Repressor of translation initiation involved in synaptic plasticity, learning and memory formation (PubMed:30765518).
Regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form of EIF4EBP2 competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation (PubMed:25533957, PubMed:30765518).
EIF4EBP2 is enriched in brain and acts as a regulator of synapse activity and neuronal stem cell renewal via its ability to repress translation initiation (By similarity).
Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (By similarity).
Regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form of EIF4EBP2 competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation (PubMed:25533957, PubMed:30765518).
EIF4EBP2 is enriched in brain and acts as a regulator of synapse activity and neuronal stem cell renewal via its ability to repress translation initiation (By similarity).
Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (By similarity).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | intracellular non-membrane-bounded organelle | |
Cellular Component | neuronal ribonucleoprotein granule | |
Cellular Component | nucleus | |
Cellular Component | postsynapse | |
Molecular Function | eukaryotic initiation factor 4E binding | |
Molecular Function | translation repressor activity | |
Biological Process | insulin receptor signaling pathway | |
Biological Process | memory | |
Biological Process | modulation of chemical synaptic transmission | |
Biological Process | negative regulation of translational initiation | |
Biological Process | regulation of synaptic plasticity | |
Biological Process | social behavior | |
Biological Process | TOR signaling | |
Biological Process | translation |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameEukaryotic translation initiation factor 4E-binding protein 2
- Short names4E-BP2 ; eIF4E-binding protein 2
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ13542
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 37 | Acidic residues do not mimic phosphorylation state. Does not induce folding of the intrinsically disordered protein; when associated with D-46 or E-46. | ||||
Sequence: T → D or E | ||||||
Mutagenesis | 39 | Abolishes folding of the intrinsically disordered protein without affecting greatly affinity for EIF4E even when the protein is fully phosphorylated; when associated with V-48. | ||||
Sequence: G → V | ||||||
Mutagenesis | 46 | Acidic residues do not mimic phosphorylation state. Does not induce folding of the intrinsically disordered protein; when associated with D-37 or E-37. | ||||
Sequence: T → D or E | ||||||
Mutagenesis | 48 | Abolishes folding of the intrinsically disordered protein without affecting greatly affinity for EIF4E even when the protein is fully phosphorylated; when associated with V-39. | ||||
Sequence: G → V | ||||||
Mutagenesis | 54-60 | Impaired binding to EIF4E. | ||||
Sequence: YDRKFLL → AAAAAAA | ||||||
Mutagenesis | 78-82 | Impaired binding to EIF4E. | ||||
Sequence: IPGVT → AAAAA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 148 variants from UniProt as well as other sources including ClinVar and dbSNP.
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_0000190516 | 1-120 | UniProt | Eukaryotic translation initiation factor 4E-binding protein 2 | |||
Sequence: MSSSAGSGHQPSQSRAIPTRTVAISDAAQLPHDYCTTPGGTLFSTTPGGTRIIYDRKFLLDRRNSPMAQTPPCHLPNIPGVTSPGTLIEDSKVEVNNLNNLNNHDRKHAVGDDAQFEMDI | |||||||
Modified residue (large scale data) | 2 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 3 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 4 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 7 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 36 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 37 | UniProt | Phosphothreonine; by MTOR | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 37 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 41 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 44 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 45 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 46 | UniProt | Phosphothreonine; by MTOR | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 46 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 50 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 65 | UniProt | Phosphoserine; by MTOR | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 65 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 70 | UniProt | Phosphothreonine; by MTOR | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 70 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 82 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 83 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 83 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 99 | UniProt | Deamidated asparagine | ||||
Sequence: N | |||||||
Modified residue | 102 | UniProt | Deamidated asparagine | ||||
Sequence: N |
Post-translational modification
Phosphorylation at Thr-37, Thr-46, Ser-65, Thr-70 and Ser-83 is mediated by MTOR and corresponds to the hyperphosphorylated form: it abolishes binding to EIF4E by inducing folding of intrinsically disordered regions (PubMed:24207126, PubMed:25533957).
First phosphorylated at Thr-37 and Thr-46 by MTOR, inducing folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000 (PubMed:24207126, PubMed:25533957).
Phosphorylated in response to insulin, EGF and PDGF
First phosphorylated at Thr-37 and Thr-46 by MTOR, inducing folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000 (PubMed:24207126, PubMed:25533957).
Phosphorylated in response to insulin, EGF and PDGF
Deamidated at Asn-99 and Asn-102 to aspartate (Asp) in brain. Deamidation promotes interaction with RPTOR, subsequent phosphorylation by mTORC1 and increased translation, leading to impair kinetics of excitatory synaptic transmission. Deamidation takes place during postnatal development, when the PI3K-Akt-mTOR signaling is reduced, suggesting it acts as a compensatory mechanism to promote translation despite attenuated PI3K-Akt-mTOR signaling in neuron development. Deamidation converts Asn residues into a mixture of Asp and isoaspartate; interactions with PCMT1 is required to prevent isoaspartate accumulation and convert isoaspartate to Asp.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Hypophosphorylated EIF4EBP2 interacts with EIF4E; phosphorylation of EIF4EBP2 by mTORC1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:21661078, PubMed:24207126, PubMed:25533957, PubMed:7935836).
Interacts with RPTOR; promoting phosphorylation by mTORC1 (By similarity).
Interacts with PCMT1; required to prevent isoaspartate accumulation and convert isoaspartate to Asp (By similarity).
Interacts with RPTOR; promoting phosphorylation by mTORC1 (By similarity).
Interacts with PCMT1; required to prevent isoaspartate accumulation and convert isoaspartate to Asp (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q13542 | EIF4E P06730 | 16 | EBI-935137, EBI-73440 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-48 | Disordered | ||||
Sequence: MSSSAGSGHQPSQSRAIPTRTVAISDAAQLPHDYCTTPGGTLFSTTPG | ||||||
Motif | 54-60 | YXXXXLphi motif | ||||
Sequence: YDRKFLL | ||||||
Region | 65-120 | Disordered | ||||
Sequence: SPMAQTPPCHLPNIPGVTSPGTLIEDSKVEVNNLNNLNNHDRKHAVGDDAQFEMDI | ||||||
Motif | 78-82 | Secondary EIF4E binding site | ||||
Sequence: IPGVT | ||||||
Motif | 116-120 | TOS motif | ||||
Sequence: FEMDI |
Domain
The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.
Intrinsically disordered protein that undergoes folding upon phosphorylation (PubMed:25533957).
Hypophosphorylated form interacts strongly with EIF4E using 1 the YXXXXLPhi motif, that undergoes a disorder-to-helix transition upon binding and 2 the secondary EIF4E binding sites (residues 78-82) (PubMed:24207126, PubMed:25533957).
Phosphorylation at Thr-37 and Thr-46 induces folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000 (PubMed:24207126, PubMed:25533957).
Hypophosphorylated form interacts strongly with EIF4E using 1 the YXXXXLPhi motif, that undergoes a disorder-to-helix transition upon binding and 2 the secondary EIF4E binding sites (residues 78-82) (PubMed:24207126, PubMed:25533957).
Phosphorylation at Thr-37 and Thr-46 induces folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000 (PubMed:24207126, PubMed:25533957).
Sequence similarities
Belongs to the eIF4E-binding protein family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length120
- Mass (Da)12,939
- Last updated1996-11-01 v1
- ChecksumB8F109261A504193
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L36056 EMBL· GenBank· DDBJ | AAA62270.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007317 EMBL· GenBank· DDBJ | AAP35981.1 EMBL· GenBank· DDBJ | mRNA | ||
BC005057 EMBL· GenBank· DDBJ | AAH05057.1 EMBL· GenBank· DDBJ | mRNA | ||
BC050633 EMBL· GenBank· DDBJ | AAH50633.1 EMBL· GenBank· DDBJ | mRNA |