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Protein

Eukaryotic translation initiation factor 4E-binding protein 1

Gene

EIF4EBP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.2 Publications

GO - Molecular functioni

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

GO - Biological processi

  • cellular response to hypoxia Source: Ensembl
  • G1/S transition of mitotic cell cycle Source: UniProtKB
  • insulin receptor signaling pathway Source: Ensembl
  • IRES-dependent translational initiation Source: Ensembl
  • lung development Source: Ensembl
  • negative regulation of protein complex assembly Source: Ensembl
  • negative regulation of translational initiation Source: UniProtKB
  • positive regulation of mitotic cell cycle Source: UniProtKB
  • response to ethanol Source: Ensembl
  • response to ischemia Source: Ensembl
  • TOR signaling Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Protein synthesis inhibitor

Keywords - Biological processi

Translation regulation

Enzyme and pathway databases

ReactomeiR-HSA-166208. mTORC1-mediated signalling.
R-HSA-72662. Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S.
SignaLinkiQ13541.
SIGNORiQ13541.

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
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:3288. EIF4EBP1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: AgBase
  • nucleoplasm Source: HPA
  • protein complex Source: Ensembl
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi37 – 371T → A: Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-46; A-65 and A-70. 1 Publication
Mutagenesisi46 – 461T → A: Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-37; A-65 and A-70. 1 Publication
Mutagenesisi57 – 571K → R: Impaired ubiquitination by the BCR(KLHL25) complex. 1 Publication
Mutagenesisi59 – 602LM → AA: Abolishes eIF4E-binding. Increased ubiquitination by the BCR(KLHL25) complex. 1 Publication
Mutagenesisi65 – 651S → A: Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-37; A-46 and A-70. 1 Publication
Mutagenesisi69 – 691K → R: Does not affect ubiquitination by the BCR(KLHL25) complex. 1 Publication
Mutagenesisi70 – 701T → A: Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-37; A-46 and A-65. 1 Publication
Mutagenesisi105 – 1051K → R: Does not affect ubiquitination by the BCR(KLHL25) complex. 1 Publication

Organism-specific databases

PharmGKBiPA27715.

Chemistry

ChEMBLiCHEMBL3351214.

Polymorphism and mutation databases

BioMutaiEIF4EBP1.
DMDMi34921508.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources1 Publication
Chaini2 – 118117Eukaryotic translation initiation factor 4E-binding protein 1PRO_0000190513Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineCombined sources1 Publication
Modified residuei37 – 371Phosphothreonine; by MTORCombined sources2 Publications
Modified residuei41 – 411PhosphothreonineCombined sources
Modified residuei44 – 441PhosphoserineBy similarity
Modified residuei46 – 461Phosphothreonine; by MTORCombined sources2 Publications
Modified residuei50 – 501PhosphothreonineCombined sources
Modified residuei54 – 541PhosphotyrosineCombined sources
Cross-linki57 – 57Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei65 – 651Phosphoserine; by DYRK2, MAPK1, MAPK3 and MTORCombined sources3 Publications
Modified residuei70 – 701Phosphothreonine; by MTORCombined sources2 Publications
Modified residuei77 – 771PhosphothreonineCombined sources
Modified residuei83 – 831PhosphoserineCombined sources
Modified residuei96 – 961PhosphoserineBy similarity
Modified residuei101 – 1011Phosphoserine; by DYRK2Combined sources1 Publication
Modified residuei112 – 1121PhosphoserineCombined sources1 Publication

Post-translational modificationi

Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.5 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-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ13541.
MaxQBiQ13541.
PaxDbiQ13541.
PeptideAtlasiQ13541.
PRIDEiQ13541.
TopDownProteomicsiQ13541.

PTM databases

iPTMnetiQ13541.
PhosphoSiteiQ13541.

Miscellaneous databases

PMAP-CutDBQ13541.

Expressioni

Gene expression databases

BgeeiENSG00000187840.
CleanExiHS_EIF4EBP1.
GenevisibleiQ13541. HS.

Organism-specific databases

HPAiCAB005032.
CAB005039.
HPA023501.

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 (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1 (PubMed:12747827).8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AGO2Q9UKV82EBI-74090,EBI-528269
EIF4EP0673011EBI-74090,EBI-73440
MTORP423452EBI-74090,EBI-359260
MtorQ9JLN92EBI-74090,EBI-1571628From a different organism.
RELQ048643EBI-74090,EBI-307352
RPTORQ8N1225EBI-74090,EBI-1567928
TCF4P158843EBI-74090,EBI-533224

GO - Molecular functioni

  • eukaryotic initiation factor 4E binding Source: AgBase

Protein-protein interaction databases

BioGridi108293. 39 interactions.
DIPiDIP-30944N.
IntActiQ13541. 19 interactions.
MINTiMINT-210160.
STRINGi9606.ENSP00000340691.

Structurei

Secondary structure

1
118
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi56 – 616Combined sources
Helixi62 – 643Combined sources
Helixi66 – 694Combined sources
Turni79 – 824Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1EJ4X-ray2.25B51-64[»]
1WKWX-ray2.10B47-66[»]
2JGBX-ray1.70B51-67[»]
2JGCX-ray2.40B51-67[»]
2V8WX-ray2.30B/F51-64[»]
2V8XX-ray2.30B/F51-64[»]
2V8YX-ray2.10B/F51-64[»]
3HXGX-ray2.10C51-67[»]
3HXIX-ray1.80C51-67[»]
3M93X-ray2.90C51-67[»]
3M94X-ray2.05C51-67[»]
3U7XX-ray2.10C/D47-66[»]
4UEDX-ray1.75B50-83[»]
5BXVX-ray2.10B/D43-84[»]
DisProtiDP00028.
ProteinModelPortaliQ13541.
SMRiQ13541. Positions 18-83.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13541.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi54 – 607YXXXXLphi motifBy similarity
Motifi114 – 1185TOS motif1 Publication

Domaini

The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.1 Publication

Sequence similaritiesi

Belongs to the eIF4E-binding protein family.Curated

Phylogenomic databases

eggNOGiENOG410J2Z0. Eukaryota.
ENOG4112779. LUCA.
GeneTreeiENSGT00390000013843.
HOGENOMiHOG000231190.
HOVERGENiHBG050425.
InParanoidiQ13541.
KOiK07205.
OMAiTEPSQNH.
OrthoDBiEOG091G0ZHJ.
PhylomeDBiQ13541.
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.

Q13541-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGGSSCSQT PSRAIPATRR VVLGDGVQLP PGDYSTTPGG TLFSTTPGGT
60 70 80 90 100
RIIYDRKFLM ECRNSPVTKT PPRDLPTIPG VTSPSSDEPP MEASQSHLRN
110
SPEDKRAGGE ESQFEMDI
Length:118
Mass (Da):12,580
Last modified:January 23, 2007 - v3
Checksum:i1682A6BA74132966
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36055 mRNA. Translation: AAA62269.1.
AB044548 mRNA. Translation: BAB18650.1.
BT007162 mRNA. Translation: AAP35826.1.
CR456769 mRNA. Translation: CAG33050.1.
AK312011 mRNA. Translation: BAG34949.1.
CH471080 Genomic DNA. Translation: EAW63341.1.
CH471080 Genomic DNA. Translation: EAW63342.1.
BC004459 mRNA. Translation: AAH04459.1.
BC058073 mRNA. Translation: AAH58073.1.
CCDSiCCDS6100.1.
PIRiS50866.
RefSeqiNP_004086.1. NM_004095.3.
UniGeneiHs.411641.

Genome annotation databases

EnsembliENST00000338825; ENSP00000340691; ENSG00000187840.
GeneIDi1978.
KEGGihsa:1978.
UCSCiuc003xks.4. human.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36055 mRNA. Translation: AAA62269.1.
AB044548 mRNA. Translation: BAB18650.1.
BT007162 mRNA. Translation: AAP35826.1.
CR456769 mRNA. Translation: CAG33050.1.
AK312011 mRNA. Translation: BAG34949.1.
CH471080 Genomic DNA. Translation: EAW63341.1.
CH471080 Genomic DNA. Translation: EAW63342.1.
BC004459 mRNA. Translation: AAH04459.1.
BC058073 mRNA. Translation: AAH58073.1.
CCDSiCCDS6100.1.
PIRiS50866.
RefSeqiNP_004086.1. NM_004095.3.
UniGeneiHs.411641.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1EJ4X-ray2.25B51-64[»]
1WKWX-ray2.10B47-66[»]
2JGBX-ray1.70B51-67[»]
2JGCX-ray2.40B51-67[»]
2V8WX-ray2.30B/F51-64[»]
2V8XX-ray2.30B/F51-64[»]
2V8YX-ray2.10B/F51-64[»]
3HXGX-ray2.10C51-67[»]
3HXIX-ray1.80C51-67[»]
3M93X-ray2.90C51-67[»]
3M94X-ray2.05C51-67[»]
3U7XX-ray2.10C/D47-66[»]
4UEDX-ray1.75B50-83[»]
5BXVX-ray2.10B/D43-84[»]
DisProtiDP00028.
ProteinModelPortaliQ13541.
SMRiQ13541. Positions 18-83.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108293. 39 interactions.
DIPiDIP-30944N.
IntActiQ13541. 19 interactions.
MINTiMINT-210160.
STRINGi9606.ENSP00000340691.

Chemistry

ChEMBLiCHEMBL3351214.

PTM databases

iPTMnetiQ13541.
PhosphoSiteiQ13541.

Polymorphism and mutation databases

BioMutaiEIF4EBP1.
DMDMi34921508.

Proteomic databases

EPDiQ13541.
MaxQBiQ13541.
PaxDbiQ13541.
PeptideAtlasiQ13541.
PRIDEiQ13541.
TopDownProteomicsiQ13541.

Protocols and materials databases

DNASUi1978.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338825; ENSP00000340691; ENSG00000187840.
GeneIDi1978.
KEGGihsa:1978.
UCSCiuc003xks.4. human.

Organism-specific databases

CTDi1978.
GeneCardsiEIF4EBP1.
HGNCiHGNC:3288. EIF4EBP1.
HPAiCAB005032.
CAB005039.
HPA023501.
MIMi602223. gene.
neXtProtiNX_Q13541.
PharmGKBiPA27715.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J2Z0. Eukaryota.
ENOG4112779. LUCA.
GeneTreeiENSGT00390000013843.
HOGENOMiHOG000231190.
HOVERGENiHBG050425.
InParanoidiQ13541.
KOiK07205.
OMAiTEPSQNH.
OrthoDBiEOG091G0ZHJ.
PhylomeDBiQ13541.
TreeFamiTF101530.

Enzyme and pathway databases

ReactomeiR-HSA-166208. mTORC1-mediated signalling.
R-HSA-72662. Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S.
SignaLinkiQ13541.
SIGNORiQ13541.

Miscellaneous databases

EvolutionaryTraceiQ13541.
GeneWikiiEIF4EBP1.
GenomeRNAii1978.
PMAP-CutDBQ13541.
PROiQ13541.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187840.
CleanExiHS_EIF4EBP1.
GenevisibleiQ13541. HS.

Family and domain databases

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

Entry informationi

Entry namei4EBP1_HUMAN
AccessioniPrimary (citable) accession number: Q13541
Secondary accession number(s): B2R502, D3DSW8, Q6IBN3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 159 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.