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Protein

Eukaryotic translation initiation factor 4E-binding protein 2

Gene

Eif4ebp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionProtein synthesis inhibitor
Biological processTranslation 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:109198 Eif4ebp2

Subcellular locationi

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)DescriptionActionsGraphical viewLength
Mutagenesisi37T → A: Impaired hyperphosphorylation. 1 Publication1
Mutagenesisi46T → A: Impaired hyperphosphorylation. 1 Publication1
Mutagenesisi70T → A: Does not greatlay affect hyperphosphorylation. 1 Publication1
Mutagenesisi99 – 102NNLN → ANLA: Abolishes deamidation and impaired interaction with RPTOR. 1 Publication4
Mutagenesisi99 – 102NNLN → DNLD: Increased interaction with RPTOR. 1 Publication4
Mutagenesisi116 – 120Missing : Abolishes interaction with RPTOR. 1 Publication5

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001905171 – 120Eukaryotic translation initiation factor 4E-binding protein 2Add BLAST120

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei37Phosphothreonine; by MTORCombined sources1 Publication1
Modified residuei46Phosphothreonine; by MTORCombined sources1 Publication1
Modified residuei65Phosphoserine; by MTORCombined sources1 Publication1
Modified residuei70Phosphothreonine; by MTORCombined sources1 Publication1
Modified residuei83PhosphoserineBy similarity1
Modified residuei99Deamidated asparagine2 Publications1
Modified residuei102Deamidated asparagine2 Publications1

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
PhosphoSitePlusiP70445

Expressioni

Tissue specificityi

Enriched in brain.1 Publication

Gene expression databases

BgeeiENSMUSG00000020091 Expressed in 273 organ(s), highest expression level in blood
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

Protein-protein interaction databases

BioGridi199422, 3 interactors
DIPiDIP-60124N
IntActiP70445, 1 interactor
STRINGi10090.ENSMUSP00000020288

Structurei

3D structure databases

ProteinModelPortaliP70445
SMRiP70445
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi54 – 60YXXXXLphi motifBy similarity7
Motifi116 – 120TOS motif1 Publication5

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
GeneTreeiENSGT00390000013843
HOGENOMiHOG000231190
HOVERGENiHBG050425
InParanoidiP70445
KOiK18644
OMAiDTTQLPH
OrthoDBiEOG091G0ZHJ
PhylomeDBiP70445
TreeFamiTF101530

Family and domain databases

InterProiView protein in InterPro
IPR008606 EIF4EBP
PfamiView protein in Pfam
PF05456 eIF_4EBP, 1 hit

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
XP_017169281.1, XM_017313792.1
XP_017169282.1, XM_017313793.1
UniGeneiMm.259516

Genome annotation databases

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

Similar proteinsi

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
XP_017169281.1, XM_017313792.1
XP_017169282.1, XM_017313793.1
UniGeneiMm.259516

3D structure databases

ProteinModelPortaliP70445
SMRiP70445
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199422, 3 interactors
DIPiDIP-60124N
IntActiP70445, 1 interactor
STRINGi10090.ENSMUSP00000020288

PTM databases

iPTMnetiP70445
PhosphoSitePlusiP70445

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
GeneTreeiENSGT00390000013843
HOGENOMiHOG000231190
HOVERGENiHBG050425
InParanoidiP70445
KOiK18644
OMAiDTTQLPH
OrthoDBiEOG091G0ZHJ
PhylomeDBiP70445
TreeFamiTF101530

Miscellaneous databases

ChiTaRSiEif4ebp2 mouse
PROiPR:P70445
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020091 Expressed in 273 organ(s), highest expression level in blood
ExpressionAtlasiP70445 baseline and differential
GenevisibleiP70445 MM

Family and domain databases

InterProiView protein in InterPro
IPR008606 EIF4EBP
PfamiView protein in Pfam
PF05456 eIF_4EBP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry namei4EBP2_MOUSE
AccessioniPrimary (citable) accession number: P70445
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: February 1, 1997
Last modified: October 10, 2018
This is version 118 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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