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Protein

Eukaryotic translation initiation factor 4E-binding protein 2

Gene

Eif4ebp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Repressor of translation initiation involved in synaptic plasticity, learning and memory formation (PubMed:16237163, PubMed:17029989). 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:17029989, PubMed:20347422, PubMed:23172145). 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 (PubMed:20347422, PubMed:24139800, PubMed:23172145). Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (PubMed:8939971).By similarity6 Publications

GO - Molecular functioni

  • eukaryotic initiation factor 4E binding Source: UniProtKB
  • translation repressor activity Source: UniProtKB

GO - Biological processi

  • cAMP-mediated signaling Source: MGI
  • insulin receptor signaling pathway Source: MGI
  • memory Source: UniProtKB
  • modulation of synaptic transmission Source: UniProtKB
  • negative regulation of translational initiation Source: UniProtKB
  • regulation of synaptic plasticity Source: UniProtKB
  • regulation of translational initiation Source: MGI
  • social behavior Source: UniProtKB
  • TOR signaling Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Protein synthesis inhibitor

Keywords - Biological processi

Translation regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Eukaryotic translation initiation factor 4E-binding protein 2By similarity
Short name:
4E-BP2By similarity
Short name:
eIF4E-binding protein 2By similarity
Alternative name(s):
Phosphorylated heat- and acid-stable protein regulated by insulin 21 Publication
Short name:
PHAS-II1 Publication
Gene namesi
Name:Eif4ebp2Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:109198. Eif4ebp2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Disruption phenotypei

Mice develop normally and are fertile. They however show defects in synaptic plasticity, impaired spatial learning and memory and conditioned fear-associative memory deficits (PubMed:16237163). Mice show behavior defects and autistic-like phenotype, characterized by social interaction deficits, altered communication and repetitive/stereotyped behaviors: they show an increased ratio of excitatory to inhibitory synaptic inputs possibly due to increased translation of neuroligin family proteins (PubMed:17029989, PubMed:23172145). Mice lacking both Eif4ebp1 and Eif4ebp2 display increased their sensitivity to diet-induced obesity (PubMed:17273556). Mice lacking both Eif4ebp1 and Eif4ebp2 show defects in myelopoiesis: mice display an increased number of immature granulocytic precursors, associated with a decreased number of mature granulocytic elements (PubMed:19175792).5 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi37 – 371T → A: Impaired hyperphosphorylation. 1 Publication
Mutagenesisi46 – 461T → A: Impaired hyperphosphorylation. 1 Publication
Mutagenesisi70 – 701T → A: Does not greatlay affect hyperphosphorylation. 1 Publication
Mutagenesisi99 – 1024NNLN → ANLA: Abolishes deamidation and impaired interaction with RPTOR. 1 Publication
Mutagenesisi99 – 1024NNLN → DNLD: Increased interaction with RPTOR. 1 Publication
Mutagenesisi116 – 1205Missing : Abolishes interaction with RPTOR. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 120120Eukaryotic translation initiation factor 4E-binding protein 2PRO_0000190517Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei37 – 371Phosphothreonine; by MTORCombined sources1 Publication
Modified residuei46 – 461Phosphothreonine; by MTORCombined sources1 Publication
Modified residuei65 – 651Phosphoserine; by MTORCombined sources1 Publication
Modified residuei70 – 701Phosphothreonine; by MTORCombined sources1 Publication
Modified residuei83 – 831PhosphoserineBy similarity
Modified residuei99 – 991Deamidated asparagine2 Publications
Modified residuei102 – 1021Deamidated asparagine2 Publications

Post-translational modificationi

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. 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. Phosphorylated in response to insulin, EGF and PDGF.By similarity1 Publication
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 (PubMed:20347422). 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 (PubMed:20424163).2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP70445.
PaxDbiP70445.
PeptideAtlasiP70445.
PRIDEiP70445.

PTM databases

iPTMnetiP70445.
PhosphoSiteiP70445.

Expressioni

Tissue specificityi

Enriched in brain.1 Publication

Gene expression databases

BgeeiENSMUSG00000020091.
ExpressionAtlasiP70445. baseline and differential.
GenevisibleiP70445. MM.

Interactioni

Subunit structurei

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. Interacts (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1 (PubMed:20347422, PubMed:23184952). Interacts with PCMT1; required to prevent isoaspartate accumulation and convert isoaspartate to Asp (PubMed:20424163).By similarity3 Publications

GO - Molecular functioni

  • eukaryotic initiation factor 4E binding Source: UniProtKB

Protein-protein interaction databases

BioGridi199422. 3 interactions.
DIPiDIP-60124N.
STRINGi10090.ENSMUSP00000020288.

Structurei

3D structure databases

ProteinModelPortaliP70445.
SMRiP70445. Positions 18-62.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi54 – 607YXXXXLphi motifBy similarity
Motifi116 – 1205TOS motif1 Publication

Domaini

The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.1 Publication
Intrinsically disordered protein that undergoes folding upon phosphorylation. 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). 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.By similarity

Sequence similaritiesi

Belongs to the eIF4E-binding protein family.Curated

Phylogenomic databases

eggNOGiENOG410J2Z0. Eukaryota.
ENOG4112779. LUCA.
HOGENOMiHOG000231190.
HOVERGENiHBG050425.
InParanoidiP70445.
KOiK18644.
OMAiVGDEAQF.
OrthoDBiEOG091G0ZHJ.
PhylomeDBiP70445.
TreeFamiTF101530.

Family and domain databases

InterProiIPR008606. EIF4EBP.
[Graphical view]
PfamiPF05456. eIF_4EBP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P70445-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSASAGGSHQ PSQSRAIPTR TVAISDAAQL PQDYCTTPGG TLFSTTPGGT
60 70 80 90 100
RIIYDRKFLL DRRNSPMAQT PPCHLPNIPG VTSPGALIED SKVEVNNLNN
110 120
LNNHDRKHAV GDEAQFEMDI
Length:120
Mass (Da):12,898
Last modified:February 1, 1997 - v1
Checksum:i0A1ACC082583F769
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75530 mRNA. Translation: AAC52899.1.
BC015082 mRNA. Translation: AAH15082.1.
CCDSiCCDS23879.1.
RefSeqiNP_034254.1. NM_010124.2.
UniGeneiMm.259516.

Genome annotation databases

EnsembliENSMUST00000020288; ENSMUSP00000020288; ENSMUSG00000020091.
ENSMUST00000167087; ENSMUSP00000131952; ENSMUSG00000020091.
GeneIDi13688.
KEGGimmu:13688.
UCSCiuc007fga.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75530 mRNA. Translation: AAC52899.1.
BC015082 mRNA. Translation: AAH15082.1.
CCDSiCCDS23879.1.
RefSeqiNP_034254.1. NM_010124.2.
UniGeneiMm.259516.

3D structure databases

ProteinModelPortaliP70445.
SMRiP70445. Positions 18-62.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199422. 3 interactions.
DIPiDIP-60124N.
STRINGi10090.ENSMUSP00000020288.

PTM databases

iPTMnetiP70445.
PhosphoSiteiP70445.

Proteomic databases

EPDiP70445.
PaxDbiP70445.
PeptideAtlasiP70445.
PRIDEiP70445.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020288; ENSMUSP00000020288; ENSMUSG00000020091.
ENSMUST00000167087; ENSMUSP00000131952; ENSMUSG00000020091.
GeneIDi13688.
KEGGimmu:13688.
UCSCiuc007fga.1. mouse.

Organism-specific databases

CTDi1979.
MGIiMGI:109198. Eif4ebp2.

Phylogenomic databases

eggNOGiENOG410J2Z0. Eukaryota.
ENOG4112779. LUCA.
HOGENOMiHOG000231190.
HOVERGENiHBG050425.
InParanoidiP70445.
KOiK18644.
OMAiVGDEAQF.
OrthoDBiEOG091G0ZHJ.
PhylomeDBiP70445.
TreeFamiTF101530.

Miscellaneous databases

ChiTaRSiEif4ebp2. mouse.
PROiP70445.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020091.
ExpressionAtlasiP70445. baseline and differential.
GenevisibleiP70445. MM.

Family and domain databases

InterProiIPR008606. EIF4EBP.
[Graphical view]
PfamiPF05456. eIF_4EBP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry namei4EBP2_MOUSE
AccessioniPrimary (citable) accession number: P70445
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: February 1, 1997
Last modified: September 7, 2016
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.