EIF4EBP2
entrez
1979
canonical
uniprot
Q13542
canonical
ensembl
ENSG00000148730
resolver
ensp
ENSP00000362314
resolver
enst
ENST00000373218
resolver
genesymbol
EIF4EBP2
resolver
hgnc
HGNC:3289
resolver
uniprot_entry
4EBP2_HUMAN
resolver
amino_acid_sequence
MSSSAGSGHQPSQSRAIPTRTVAISDAAQLPHDYCTTPGGTLFSTTPGGTRIIYDRKFLLDRRNSPMAQTPPCHLPNIPGVTSPGTLIEDSKVEVNNLNNLNNHDRKHAVGDDAQFEMDI
uniprot
proteins
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). {ECO:0000250|UniProtKB:P70445, ECO:0000269|PubMed:25533957, ECO:0000269|PubMed:30765518}.
uniprot
proteins
mass_dalton
12939
uniprot
proteins
mutagenesis
MUTAGEN 37; /note="T->D,E: Acidic residues do not mimic phosphorylation state. Does not induce folding of the intrinsically disordered protein; when associated with D-46 or E-46."; /evidence="ECO:0000269|PubMed:25533957"; MUTAGEN 39; /note="G->V: 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."; /evidence="ECO:0000269|PubMed:25533957"; MUTAGEN 46; /note="T->D,E: Acidic residues do not mimic phosphorylation state. Does not induce folding of the intrinsically disordered protein; when associated with D-37 or E-37."; /evidence="ECO:0000269|PubMed:25533957"; MUTAGEN 48; /note="G->V: 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."; /evidence="ECO:0000269|PubMed:25533957"; MUTAGEN 54..60; /note="YDRKFLL->AAAAAAA: Impaired binding to EIF4E."; /evidence="ECO:0000269|PubMed:24207126"; MUTAGEN 78..82; /note="IPGVT->AAAAA: Impaired binding to EIF4E."; /evidence="ECO:0000269|PubMed:24207126
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:21661078, ECO:0000269|PubMed:24207126, ECO:0000269|PubMed:25533957}.; PTM: 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. {ECO:0000250|UniProtKB:P70445}.
uniprot
proteins
protein_family
EIF4E-binding protein family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
21661078
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24207126
uniprot
proteins
pubmed
25533957
uniprot
proteins
pubmed
30765518
uniprot
proteins
pubmed
7935836
uniprot
proteins
sequence_length
120
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P70445}. Nucleus {ECO:0000250|UniProtKB:P70445}.
uniprot
proteins