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Protein

Eukaryotic translation initiation factor 4E-binding protein 1

Gene

Eif4ebp1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form 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 (By similarity). Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (PubMed:7939721).By similarity1 Publication

GO - Molecular functioni

  • eukaryotic initiation factor 4E binding Source: RGD
  • protein phosphatase 2A binding Source: RGD
  • translation initiation factor binding Source: RGD
  • translation repressor activity Source: UniProtKB

GO - Biological processi

  • cellular response to dexamethasone stimulus Source: Ensembl
  • cellular response to hypoxia Source: RGD
  • insulin receptor signaling pathway Source: Ensembl
  • IRES-dependent translational initiation of linear mRNA Source: Ensembl
  • lung development Source: RGD
  • negative regulation of protein complex assembly Source: RGD
  • negative regulation of translational initiation Source: RGD
  • response to amino acid starvation Source: RGD
  • response to ethanol Source: RGD
  • response to ischemia Source: RGD
  • TOR signaling Source: UniProtKB

Keywordsi

Molecular functionProtein synthesis inhibitor
Biological processTranslation regulation

Enzyme and pathway databases

ReactomeiR-RNO-166208 mTORC1-mediated signalling
R-RNO-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S

Names & Taxonomyi

Protein namesi
Recommended name:
Eukaryotic translation initiation factor 4E-binding protein 1
Short name:
4E-BP1
Short name:
eIF4E-binding protein 1
Alternative name(s):
Phosphorylated heat- and acid-stable protein regulated by insulin 1
Short name:
PHAS-I
Gene namesi
OrganismiRattus norvegicus (Rat)Imported
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 16

Organism-specific databases

RGDi620259 Eif4ebp1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi64S → A: Decreases phosphorylation by MAPK1 and MAPK3. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001905152 – 117Eukaryotic translation initiation factor 4E-binding protein 1Add BLAST116

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei36PhosphothreonineCombined sources1
Modified residuei40PhosphothreonineBy similarity1
Modified residuei43PhosphoserineBy similarity1
Modified residuei45Phosphothreonine; by MTORBy similarity1
Modified residuei49PhosphothreonineBy similarity1
Modified residuei53PhosphotyrosineBy similarity1
Cross-linki56Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei64Phosphoserine; by DYRK2, MAPK1, MAPK3 and MTOR1 Publication1
Modified residuei69Phosphothreonine; by MTORBy similarity1
Modified residuei76PhosphothreonineBy similarity1
Modified residuei82PhosphoserineBy similarity1
Modified residuei95PhosphoserineBy similarity1
Modified residuei99PhosphoserineBy similarity1
Modified residuei100Phosphoserine; by DYRK2By similarity1
Modified residuei111PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylation at Thr-36, Thr-45, Ser-64 and Thr-69, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.2 Publications
Ubiquitinated: when eIF4E levels are low, hypophosphorylated form is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation and serving as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or associated with eIF4E.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ62622
PRIDEiQ62622

PTM databases

iPTMnetiQ62622
PhosphoSitePlusiQ62622

Miscellaneous databases

PMAP-CutDBiQ62622

Expressioni

Tissue specificityi

Expressed in all tissues examined; highest levels in fat and skeletal tissue, lowest levels in kidney.2 Publications

Gene expression databases

BgeeiENSRNOG00000012582
GenevisibleiQ62622 RN

Interactioni

Subunit structurei

Hypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:7939721). Interacts (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
MtorP423463EBI-7010328,EBI-1571489

GO - Molecular functioni

  • eukaryotic initiation factor 4E binding Source: RGD
  • protein phosphatase 2A binding Source: RGD
  • translation initiation factor binding Source: RGD

Protein-protein interaction databases

BioGridi250521, 6 interactors
DIPiDIP-267N
ELMiQ62622
IntActiQ62622, 1 interactor
MINTiQ62622
STRINGi10116.ENSRNOP00000016885

Structurei

3D structure databases

SMRiQ62622
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi53 – 59YXXXXLphi motifBy similarity7
Motifi113 – 117TOS motifBy similarity5

Domaini

The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.By similarity

Sequence similaritiesi

Belongs to the eIF4E-binding protein family.Curated

Phylogenomic databases

eggNOGiENOG410J2Z0 Eukaryota
ENOG4112779 LUCA
GeneTreeiENSGT00390000013843
HOGENOMiHOG000231190
HOVERGENiHBG050425
InParanoidiQ62622
KOiK07205
OMAiPMMTRKI
OrthoDBiEOG091G0ZHJ
PhylomeDBiQ62622
TreeFamiTF101530

Family and domain databases

InterProiView protein in InterPro
IPR008606 EIF4EBP
IPR037582 EIF4EBP1
PANTHERiPTHR12669:SF14 PTHR12669:SF14, 1 hit
PfamiView protein in Pfam
PF05456 eIF_4EBP, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q62622-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAGSSCSQT PSRAIPTRRV ALGDGVQLPP GDYSTTPGGT LFSTTPGGTR
60 70 80 90 100
IIYDRKFLME CRNSPVAKTP PKDLPTIPGV TSPTSDEPPM QASQSHLHSS
110
PEDKRAGGEE SQFEMDI
Length:117
Mass (Da):12,404
Last modified:January 23, 2007 - v3
Checksum:i3449D57B09FA101A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19R → N AA sequence (PubMed:8170978).Curated1
Sequence conflicti69T → P AA sequence (PubMed:8170978).Curated1
Sequence conflicti75P → L AA sequence (PubMed:8170978).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U05014 mRNA Translation: AAA86938.1
PIRiA55258
RefSeqiNP_446309.1, NM_053857.2
UniGeneiRn.11161

Genome annotation databases

EnsembliENSRNOT00000016885; ENSRNOP00000016885; ENSRNOG00000012582
GeneIDi116636
KEGGirno:116636
UCSCiRGD:620259 rat

Similar proteinsi

Entry informationi

Entry namei4EBP1_RAT
AccessioniPrimary (citable) accession number: Q62622
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 130 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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