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Q62622

- 4EBP1_RAT

UniProt

Q62622 - 4EBP1_RAT

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Protein

Eukaryotic translation initiation factor 4E-binding protein 1

Gene

Eif4ebp1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  1. eukaryotic initiation factor 4E binding Source: RGD
  2. translation initiation factor binding Source: RGD
  3. translation repressor activity Source: UniProtKB

GO - Biological processi

  1. G1/S transition of mitotic cell cycle Source: Ensembl
  2. insulin receptor signaling pathway Source: Ensembl
  3. lung development Source: RGD
  4. negative regulation of protein complex assembly Source: RGD
  5. negative regulation of translational initiation Source: RGD
  6. positive regulation of mitotic cell cycle Source: Ensembl
  7. response to ethanol Source: RGD
  8. response to ischemia Source: RGD
  9. TOR signaling Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Protein synthesis inhibitor

Keywords - Biological processi

Translation regulation

Enzyme and pathway databases

ReactomeiREACT_219577. 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
Name:Eif4ebp1
OrganismiRattus norvegicus (Rat)Imported
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 16

Organism-specific databases

RGDi620259. Eif4ebp1.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: RGD
  2. nucleus Source: RGD
  3. protein complex Source: RGD
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi64 – 641S → A: Decreases phosphorylation by MAPK1 and MAPK3. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 117116Eukaryotic translation initiation factor 4E-binding protein 1PRO_0000190515Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei36 – 361Phosphothreonine; by MTORBy similarity
Modified residuei40 – 401PhosphothreonineBy similarity
Modified residuei45 – 451Phosphothreonine; by MTORBy similarity
Modified residuei49 – 491PhosphothreonineBy similarity
Modified residuei53 – 531PhosphotyrosineBy similarity
Cross-linki56 – 56Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei64 – 641Phosphoserine; by DYRK2, MAPK1, MAPK3 and MTOR1 Publication
Modified residuei69 – 691Phosphothreonine; by MTORBy similarity
Modified residuei82 – 821PhosphoserineBy similarity
Modified residuei100 – 1001Phosphoserine; by DYRK2By similarity
Modified residuei111 – 1111PhosphoserineBy similarity

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).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ62622.

PTM databases

PhosphoSiteiQ62622.

Miscellaneous databases

PMAP-CutDBQ62622.

Expressioni

Tissue specificityi

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

Gene expression databases

GenevestigatoriQ62622.

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. Interacts with RPTOR.1 Publication

Protein-protein interaction databases

BioGridi250521. 5 interactions.
DIPiDIP-267N.
MINTiMINT-94776.
STRINGi10116.ENSRNOP00000016885.

Family & Domainsi

Sequence similaritiesi

Belongs to the eIF4E-binding protein family.Curated

Phylogenomic databases

eggNOGiNOG78084.
GeneTreeiENSGT00390000013843.
HOGENOMiHOG000231190.
HOVERGENiHBG050425.
InParanoidiQ62622.
KOiK07205.
OMAiNHLRNSP.
OrthoDBiEOG7B31Q1.
PhylomeDBiQ62622.
TreeFamiTF101530.

Family and domain databases

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

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti19 – 191R → N AA sequence (PubMed:8170978)Curated
Sequence conflicti69 – 691T → P AA sequence (PubMed:8170978)Curated
Sequence conflicti75 – 751P → L AA sequence (PubMed:8170978)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U05014 mRNA. Translation: AAA86938.1 .
PIRi A55258.
RefSeqi NP_446309.1. NM_053857.2.
UniGenei Rn.11161.

3D structure databases

ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 250521. 5 interactions.
DIPi DIP-267N.
MINTi MINT-94776.
STRINGi 10116.ENSRNOP00000016885.

PTM databases

PhosphoSitei Q62622.

Proteomic databases

PRIDEi Q62622.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000016885 ; ENSRNOP00000016885 ; ENSRNOG00000012582 .
GeneIDi 116636.
KEGGi rno:116636.
UCSCi RGD:620259. rat.

Organism-specific databases

CTDi 1978.
RGDi 620259. Eif4ebp1.

Phylogenomic databases

eggNOGi NOG78084.
GeneTreei ENSGT00390000013843.
HOGENOMi HOG000231190.
HOVERGENi HBG050425.
InParanoidi Q62622.
KOi K07205.
OMAi NHLRNSP.
OrthoDBi EOG7B31Q1.
PhylomeDBi Q62622.
TreeFami TF101530.

Enzyme and pathway databases

Reactomei REACT_219577. Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S.

Miscellaneous databases

NextBioi 619343.
PMAP-CutDB Q62622.
PROi Q62622.

Gene expression databases

Genevestigatori Q62622.

Family and domain databases

InterProi IPR008606. EIF4EBP.
[Graphical view ]
Pfami PF05456. eIF_4EBP. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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-Dawley1 Publication.
    Tissue: Adipocyte1 Publication and Skeletal muscleImported.
  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.

Entry informationi

Entry namei4EBP1_RAT
AccessioniPrimary (citable) accession number: Q62622
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: January 23, 2007
Last modified: October 29, 2014
This is version 96 of the entry and version 3 of the sequence. [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

External Data

Dasty 3