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Protein

Eukaryotic translation initiation factor 4E-binding protein 1

Gene

EIF4EBP1

Organism
Homo sapiens (Human)
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. 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

Keywordsi

Molecular functionProtein synthesis inhibitor
Biological processTranslation 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

EuPathDBiHostDB:ENSG00000187840.4
HGNCiHGNC:3288 EIF4EBP1
MIMi602223 gene
neXtProtiNX_Q13541

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
Mutagenesisi37T → A: Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-46; A-65 and A-70. 1 Publication1
Mutagenesisi46T → A: Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-37; A-65 and A-70. 1 Publication1
Mutagenesisi57K → R: Impaired ubiquitination by the BCR(KLHL25) complex. 1 Publication1
Mutagenesisi59 – 60LM → AA: Abolishes eIF4E-binding. Increased ubiquitination by the BCR(KLHL25) complex. 1 Publication2
Mutagenesisi65S → A: Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-37; A-46 and A-70. 1 Publication1
Mutagenesisi69K → R: Does not affect ubiquitination by the BCR(KLHL25) complex. 1 Publication1
Mutagenesisi70T → A: Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-37; A-46 and A-65. 1 Publication1
Mutagenesisi105K → R: Does not affect ubiquitination by the BCR(KLHL25) complex. 1 Publication1

Organism-specific databases

DisGeNETi1978
OpenTargetsiENSG00000187840
PharmGKBiPA27715

Chemistry databases

ChEMBLiCHEMBL3351214

Polymorphism and mutation databases

BioMutaiEIF4EBP1
DMDMi34921508

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001905132 – 118Eukaryotic translation initiation factor 4E-binding protein 1Add BLAST117

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei37Phosphothreonine; by MTORCombined sources2 Publications1
Modified residuei41PhosphothreonineCombined sources1
Modified residuei44PhosphoserineBy similarity1
Modified residuei46Phosphothreonine; by MTORCombined sources2 Publications1
Modified residuei50PhosphothreonineCombined sources1
Modified residuei54PhosphotyrosineCombined sources1
Cross-linki57Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei65Phosphoserine; by DYRK2, MAPK1, MAPK3 and MTORCombined sources3 Publications1
Modified residuei70Phosphothreonine; by MTORCombined sources2 Publications1
Modified residuei77PhosphothreonineCombined sources1
Modified residuei83PhosphoserineCombined sources1
Modified residuei96PhosphoserineBy similarity1
Modified residuei101Phosphoserine; by DYRK2Combined sources1 Publication1
Modified residuei112PhosphoserineCombined sources1 Publication1

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
ProteomicsDBi59525
TopDownProteomicsiQ13541

PTM databases

iPTMnetiQ13541
PhosphoSitePlusiQ13541

Miscellaneous databases

PMAP-CutDBiQ13541

Expressioni

Gene expression databases

BgeeiENSG00000187840 Expressed in 207 organ(s), highest expression level in body of pancreas
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108293, 44 interactors
DIPiDIP-30944N
ELMiQ13541
IntActiQ13541, 25 interactors
MINTiQ13541
STRINGi9606.ENSP00000340691

Structurei

Secondary structure

1118
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00028
ProteinModelPortaliQ13541
SMRiQ13541
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13541

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi54 – 60YXXXXLphi motifBy similarity7
Motifi114 – 118TOS motif1 Publication5

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
OMAiPMMTRKI
OrthoDBiEOG091G0ZHJ
PhylomeDBiQ13541
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.

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

Similar proteinsi

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EJ4X-ray2.25B51-64[»]
1EJHX-ray2.20E/F/G/H54-66[»]
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[»]
5EKVX-ray3.61B/D51-64[»]
5NVNX-ray1.90B/D50-83[»]
5WBJX-ray3.00T99-118[»]
6BCUelectron microscopy3.43X/Z1-118[»]
6BCXelectron microscopy3.00X/Z1-118[»]
DisProtiDP00028
ProteinModelPortaliQ13541
SMRiQ13541
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108293, 44 interactors
DIPiDIP-30944N
ELMiQ13541
IntActiQ13541, 25 interactors
MINTiQ13541
STRINGi9606.ENSP00000340691

Chemistry databases

ChEMBLiCHEMBL3351214

PTM databases

iPTMnetiQ13541
PhosphoSitePlusiQ13541

Polymorphism and mutation databases

BioMutaiEIF4EBP1
DMDMi34921508

Proteomic databases

EPDiQ13541
MaxQBiQ13541
PaxDbiQ13541
PeptideAtlasiQ13541
PRIDEiQ13541
ProteomicsDBi59525
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
DisGeNETi1978
EuPathDBiHostDB:ENSG00000187840.4
GeneCardsiEIF4EBP1
HGNCiHGNC:3288 EIF4EBP1
HPAiCAB005032
CAB005039
HPA023501
MIMi602223 gene
neXtProtiNX_Q13541
OpenTargetsiENSG00000187840
PharmGKBiPA27715
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J2Z0 Eukaryota
ENOG4112779 LUCA
GeneTreeiENSGT00390000013843
HOGENOMiHOG000231190
HOVERGENiHBG050425
InParanoidiQ13541
KOiK07205
OMAiPMMTRKI
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-CutDBiQ13541
PROiPR:Q13541
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187840 Expressed in 207 organ(s), highest expression level in body of pancreas
CleanExiHS_EIF4EBP1
GenevisibleiQ13541 HS

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
ProtoNetiSearch...

Entry informationi

Entry namei4EBP1_HUMAN
AccessioniPrimary (citable) accession number: Q13541
Secondary accession number(s): B2R502, D3DSW8, Q6IBN3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 177 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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