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Q62622 (4EBP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Eif4ebp1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length117 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways. Ref.2

Subunit structure

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. Interacts with RPTOR. Ref.2

Tissue specificity

Expressed in all tissues examined; highest levels in fat and skeletal tissue, lowest levels in kidney. Ref.1 Ref.2

Post-translational modification

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. Ref.1 Ref.2

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. Ref.1 Ref.2

Sequence similarities

Belongs to the eIF4E-binding protein family.

Ontologies

Keywords
   Biological processTranslation regulation
   Molecular functionProtein synthesis inhibitor
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

TOR signaling

Inferred from sequence or structural similarity. Source: UniProtKB

insulin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

lung development

Inferred from expression pattern PubMed 18952566. Source: RGD

negative regulation of protein complex assembly

Inferred from mutant phenotype PubMed 11865047. Source: RGD

negative regulation of translational initiation

Inferred from mutant phenotype PubMed 11865047. Source: RGD

positive regulation of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from expression pattern PubMed 15388509. Source: RGD

response to ischemia

Inferred from expression pattern PubMed 20736160. Source: RGD

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 18952566. Source: RGD

nucleus

Inferred from direct assay PubMed 18952566. Source: RGD

protein complex

Inferred from direct assay PubMed 18952566. Source: RGD

   Molecular_functioneukaryotic initiation factor 4E binding

Inferred from physical interaction PubMed 18952566. Source: RGD

translation initiation factor binding

Inferred from physical interaction PubMed 11865047. Source: RGD

translation repressor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 117116Eukaryotic translation initiation factor 4E-binding protein 1
PRO_0000190515

Amino acid modifications

Modified residue21N-acetylserine By similarity Ref.1
Modified residue361Phosphothreonine; by MTOR By similarity
Modified residue401Phosphothreonine By similarity
Modified residue451Phosphothreonine; by MTOR By similarity
Modified residue491Phosphothreonine By similarity
Modified residue531Phosphotyrosine By similarity
Modified residue641Phosphoserine; by DYRK2, MAPK1, MAPK3 and MTOR Ref.2
Modified residue691Phosphothreonine; by MTOR By similarity
Modified residue821Phosphoserine By similarity
Modified residue1001Phosphoserine; by DYRK2 By similarity
Modified residue1111Phosphoserine By similarity
Cross-link56Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Mutagenesis641S → A: Decreases phosphorylation by MAPK1 and MAPK3. Ref.2
Sequence conflict191R → N AA sequence Ref.1
Sequence conflict691T → P AA sequence Ref.1
Sequence conflict751P → L AA sequence Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q62622 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 3449D57B09FA101A

FASTA11712,404
        10         20         30         40         50         60 
MSAGSSCSQT PSRAIPTRRV ALGDGVQLPP GDYSTTPGGT LFSTTPGGTR IIYDRKFLME 

        70         80         90        100        110 
CRNSPVAKTP PKDLPTIPGV TSPTSDEPPM QASQSHLHSS PEDKRAGGEE SQFEMDI 

« Hide

References

[1]"Molecular cloning and tissue distribution of PHAS-I, an intracellular target for insulin and growth factors."
Hu C., Pang S., Kong X., Velleca M., Lawrence J.C. Jr.
Proc. Natl. Acad. Sci. U.S.A. 91:3730-3734(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 18-33; 43-53; 62-80 AND 98-117, PHOSPHORYLATION, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Adipocyte and Skeletal muscle.
[2]"PHAS-I as a link between mitogen-activated protein kinase and translation initiation."
Lin T.-A., Kong X., Haystead T.A.J., Pause A., Belsham G.J., Sonenberg N., Lawrence J.C. Jr.
Science 266:653-656(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EIF4E, PHOSPHORYLATION AT SER-64 BY MAPK1 AND MAPK3, MUTAGENESIS OF SER-64.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U05014 mRNA. Translation: AAA86938.1.
PIRA55258.
RefSeqNP_446309.1. NM_053857.2.
UniGeneRn.11161.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid250521. 3 interactions.
DIPDIP-267N.
MINTMINT-94776.
STRING10116.ENSRNOP00000016885.

PTM databases

PhosphoSiteQ62622.

Proteomic databases

PRIDEQ62622.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000016885; ENSRNOP00000016885; ENSRNOG00000012582.
GeneID116636.
KEGGrno:116636.
UCSCRGD:620259. rat.

Organism-specific databases

CTD1978.
RGD620259. Eif4ebp1.

Phylogenomic databases

eggNOGNOG78084.
GeneTreeENSGT00390000013843.
HOGENOMHOG000231190.
HOVERGENHBG050425.
InParanoidQ62622.
KOK07205.
OMANHLRNSP.
OrthoDBEOG7B31Q1.
PhylomeDBQ62622.
TreeFamTF101530.

Gene expression databases

GenevestigatorQ62622.

Family and domain databases

InterProIPR008606. EIF4EBP.
[Graphical view]
PANTHERPTHR12669. PTHR12669. 1 hit.
PfamPF05456. eIF_4EBP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio619343.
PMAP-CutDBQ62622.
PROQ62622.

Entry information

Entry name4EBP1_RAT
AccessionPrimary (citable) accession number: Q62622
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 92 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families