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Protein

Eukaryotic translation initiation factor 4E

Gene

EIF4E

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.2 Publications

Caution

Was originally thought to be phosphorylated on Ser-53 (PubMed:3112145); this was later shown to be wrong (PubMed:7665584).2 Publications

GO - Molecular functioni

  • enzyme binding Source: AgBase
  • eukaryotic initiation factor 4G binding Source: AgBase
  • repressing transcription factor binding Source: AgBase
  • RNA 7-methylguanosine cap binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • RNA cap binding Source: ProtInc
  • translation initiation factor activity Source: UniProtKB

GO - Biological processi

  • G1/S transition of mitotic cell cycle Source: UniProtKB
  • mRNA export from nucleus Source: Reactome
  • positive regulation of mitotic cell cycle Source: UniProtKB
  • regulation of translation Source: UniProtKB
  • RNA export from nucleus Source: Reactome
  • translational initiation Source: Reactome
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionInitiation factor, RNA-binding
Biological processHost-virus interaction, Protein biosynthesis, Translation regulation

Enzyme and pathway databases

ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-159227 Transport of the SLBP independent Mature mRNA
R-HSA-159230 Transport of the SLBP Dependant Mature mRNA
R-HSA-159231 Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-166208 mTORC1-mediated signalling
R-HSA-429947 Deadenylation of mRNA
R-HSA-72649 Translation initiation complex formation
R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
R-HSA-72702 Ribosomal scanning and start codon recognition
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit
SignaLinkiP06730
SIGNORiP06730

Names & Taxonomyi

Protein namesi
Recommended name:
Eukaryotic translation initiation factor 4E
Short name:
eIF-4E
Short name:
eIF4E
Alternative name(s):
eIF-4F 25 kDa subunit
mRNA cap-binding protein
Gene namesi
Name:EIF4E
Synonyms:EIF4EL1, EIF4F
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000151247.12
HGNCiHGNC:3287 EIF4E
MIMi133440 gene
neXtProtiNX_P06730

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

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Autism 19 (AUTS19)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry. A heterozygous single-nucleotide insertion has been found in families affected by autism. The variant results in increased promoter activity and is involved in disease pathogenesis through EIF4E deregulation (PubMed:19556253).1 Publication
Disease descriptionA complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation.
See also OMIM:615091
A chromosomal aberration involving EIF4E has been found in a patient with classic autism. Translocation t(45)(q23q31.3). The breakpoint on chromosome 4 is located 56 kb downstream of EIF4E (PubMed:19556253).1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi53S → A or D: No effect on phosphorylation level nor incorporation into eIF4F complex. 2 Publications1
Mutagenesisi73W → A: Abolishes binding to EIF4EBP1. 1 Publication1
Mutagenesisi102W → L: Decrease in mRNA cap binding; when associated with A-105. 1 Publication1
Mutagenesisi103E → A: No effect. 1 Publication1
Mutagenesisi104D → A: No effect. 1 Publication1
Mutagenesisi105E → A: Decrease in mRNA cap binding; when associated with L-102. 1 Publication1
Mutagenesisi119K → A: Higher affinity for EIF4G1. 1 Publication1

Keywords - Diseasei

Autism, Autism spectrum disorder

Organism-specific databases

DisGeNETi1977
MalaCardsiEIF4E
MIMi615091 phenotype
OpenTargetsiENSG00000151247
Orphaneti106 Autism
PharmGKBiPA27714

Chemistry databases

ChEMBLiCHEMBL4848
DrugBankiDB01649 7-Methyl-Gpppa
DB02716 7-Methyl-Guanosine-5'-Triphosphate
DB01960 7n-Methyl-8-Hydroguanosine-5'-Diphosphate
DB05165 LY2275796

Polymorphism and mutation databases

BioMutaiEIF4E
DMDMi1352435

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001936342 – 217Eukaryotic translation initiation factor 4EAdd BLAST216

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei22PhosphothreonineCombined sources1
Modified residuei209Phosphoserine; by PKC and MKNK23 Publications1

Post-translational modificationi

Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex.7 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP06730
MaxQBiP06730
PeptideAtlasiP06730
PRIDEiP06730
ProteomicsDBi51914
51915 [P06730-2]
51916 [P06730-3]
TopDownProteomicsiP06730-1 [P06730-1]

2D gel databases

OGPiP06730
REPRODUCTION-2DPAGEiIPI00027485

PTM databases

iPTMnetiP06730
PhosphoSitePlusiP06730
SwissPalmiP06730

Expressioni

Gene expression databases

BgeeiENSG00000151247
CleanExiHS_EIF4E
ExpressionAtlasiP06730 baseline and differential
GenevisibleiP06730 HS

Organism-specific databases

HPAiCAB004077
CAB016316
HPA051311

Interactioni

Subunit structurei

eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. EIF4E is also known to interact with other partners. The interaction with EIF4ENIF1 mediates the import into the nucleus. Hypophosphorylated EIF4EBP1, EIF4EBP2 and EIF4EBP3 compete with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:24207126, PubMed:25533957, PubMed:21661078). Rapamycin can attenuate insulin stimulation, mediated by FKBPs. Interacts mutually exclusive with EIF4A1 or EIF4A2. Interacts with NGDN and PIWIL2. Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1. Interacts directly with CYFIP1. Interacts with CLOCK (By similarity). Binds to MKNK2 in nucleus. Interacts with LIMD1, WTIP and AJUBA. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with LARP1. Interacts with METTL3 (PubMed:27117702). Interacts with RBM24; this interaction prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly of translation initiation complex (PubMed:29358667).By similarity15 Publications
(Microbial infection) Interacts with Lassa virus Z protein.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: AgBase
  • eukaryotic initiation factor 4G binding Source: AgBase
  • repressing transcription factor binding Source: AgBase

Protein-protein interaction databases

BioGridi108292, 51 interactors
CORUMiP06730
DIPiDIP-22N
ELMiP06730
IntActiP06730, 45 interactors
MINTiP06730

Chemistry databases

BindingDBiP06730

Structurei

Secondary structure

1217
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi31 – 33Combined sources3
Beta strandi38 – 49Combined sources12
Beta strandi51 – 53Combined sources3
Helixi56 – 59Combined sources4
Beta strandi60 – 68Combined sources9
Helixi69 – 82Combined sources14
Beta strandi89 – 95Combined sources7
Beta strandi100 – 103Combined sources4
Turni105 – 109Combined sources5
Beta strandi111 – 116Combined sources6
Helixi119 – 122Combined sources4
Turni123 – 125Combined sources3
Helixi126 – 138Combined sources13
Turni139 – 142Combined sources4
Helixi143 – 148Combined sources6
Beta strandi149 – 155Combined sources7
Beta strandi162 – 168Combined sources7
Helixi173 – 187Combined sources15
Beta strandi191 – 193Combined sources3
Beta strandi196 – 199Combined sources4
Helixi200 – 204Combined sources5
Beta strandi205 – 207Combined sources3
Turni208 – 210Combined sources3
Beta strandi214 – 216Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IPBX-ray2.00A1-217[»]
1IPCX-ray2.00A1-217[»]
1WKWX-ray2.10A27-217[»]
2GPQNMR-A1-217[»]
2V8WX-ray2.30A/E1-217[»]
2V8XX-ray2.30A/E1-217[»]
2V8YX-ray2.10A/E1-217[»]
2W97X-ray2.29A/B1-217[»]
3AM7X-ray2.20A27-217[»]
3TF2X-ray2.10A/B/C/D1-217[»]
3U7XX-ray2.10A/B1-217[»]
4AZAX-ray2.16A/C1-217[»]
4BEAX-ray2.57A1-217[»]
4DT6X-ray2.60A1-217[»]
4DUMX-ray2.95A1-217[»]
4TPWX-ray1.50A/B28-217[»]
4TQBX-ray1.59A/B28-217[»]
4TQCX-ray1.80A/B28-217[»]
4UEDX-ray1.75A36-217[»]
5EHCX-ray2.40A1-217[»]
5EI3X-ray1.71A1-217[»]
5EIRX-ray2.69A1-217[»]
5EKVX-ray3.61A/C1-217[»]
5GW6X-ray1.97A23-217[»]
5T46X-ray1.53A/C1-217[»]
ProteinModelPortaliP06730
SMRiP06730
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06730

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni37 – 40EIF4EBP1/2/3 binding4
Regioni56 – 577-methylguanosine-containing mRNA cap binding2
Regioni73 – 77EIF4EBP1/2/3 binding5
Regioni102 – 1037-methylguanosine-containing mRNA cap binding2
Regioni132 – 139EIF4EBP1/2/3 binding8
Regioni157 – 1627-methylguanosine-containing mRNA cap binding6
Regioni205 – 2077-methylguanosine-containing mRNA cap binding3

Sequence similaritiesi

Phylogenomic databases

GeneTreeiENSGT00520000055549
HOGENOMiHOG000186751
HOVERGENiHBG006130
InParanoidiP06730
KOiK03259
OMAiMKMTIGY
OrthoDBiEOG091G0IVA
PhylomeDBiP06730
TreeFamiTF101526

Family and domain databases

Gene3Di3.30.760.10, 1 hit
InterProiView protein in InterPro
IPR023398 TIF_eIF4e-like
IPR001040 TIF_eIF_4E
IPR019770 TIF_eIF_4E_CS
PANTHERiPTHR11960 PTHR11960, 1 hit
PfamiView protein in Pfam
PF01652 IF4E, 1 hit
SUPFAMiSSF55418 SSF55418, 1 hit
PROSITEiView protein in PROSITE
PS00813 IF4E, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P06730-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MATVEPETTP TPNPPTTEEE KTESNQEVAN PEHYIKHPLQ NRWALWFFKN
60 70 80 90 100
DKSKTWQANL RLISKFDTVE DFWALYNHIQ LSSNLMPGCD YSLFKDGIEP
110 120 130 140 150
MWEDEKNKRG GRWLITLNKQ QRRSDLDRFW LETLLCLIGE SFDDYSDDVC
160 170 180 190 200
GAVVNVRAKG DKIAIWTTEC ENREAVTHIG RVYKERLGLP PKIVIGYQSH
210
ADTATKSGST TKNRFVV
Length:217
Mass (Da):25,097
Last modified:February 1, 1996 - v2
Checksum:iB869B8DE615E699D
GO
Isoform 2 (identifier: P06730-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     133-133: T → TRWDLAMLPRLVSNFWPQVILPLQPPKVLELQ

Note: No experimental confirmation available.
Show »
Length:248
Mass (Da):28,778
Checksum:i3869E3249A241190
GO
Isoform 3 (identifier: P06730-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MATVEP → MLDLTSRGQVGTSRRMAEAACSAHFL

Note: No experimental confirmation available.
Show »
Length:237
Mass (Da):27,260
Checksum:iD4925235C678DE08
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti127D → N in AAH12611 (PubMed:15489334).Curated1

Mass spectrometryi

Molecular mass is 24964.3 Da from positions 2 - 217. Determined by ESI. 1 Publication
Molecular mass is 24960 Da from positions 2 - 217. Determined by ESI. 1 Publication

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0435911 – 6MATVEP → MLDLTSRGQVGTSRRMAEAA CSAHFL in isoform 3. 1 Publication6
Alternative sequenceiVSP_042014133T → TRWDLAMLPRLVSNFWPQVI LPLQPPKVLELQ in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M15353 mRNA Translation: AAC13647.1
AK300982 mRNA Translation: BAH13387.1
AC019131 Genomic DNA No translation available.
AC093836 Genomic DNA No translation available.
BC012611 mRNA Translation: AAH12611.1
BC035166 mRNA Translation: AAH35166.1
BC043226 mRNA Translation: AAH43226.1
BM849222 mRNA No translation available.
CCDSiCCDS34031.1 [P06730-1]
CCDS47109.1 [P06730-3]
CCDS54779.1 [P06730-2]
PIRiA26411
RefSeqiNP_001124150.1, NM_001130678.2 [P06730-3]
NP_001124151.1, NM_001130679.2 [P06730-2]
NP_001317946.1, NM_001331017.1
NP_001959.1, NM_001968.4 [P06730-1]
UniGeneiHs.13211
Hs.249718

Genome annotation databases

EnsembliENST00000280892; ENSP00000280892; ENSG00000151247 [P06730-3]
ENST00000450253; ENSP00000389624; ENSG00000151247 [P06730-1]
ENST00000505992; ENSP00000425561; ENSG00000151247 [P06730-2]
GeneIDi1977
KEGGihsa:1977
UCSCiuc003hue.3 human [P06730-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

Similar proteinsi

Entry informationi

Entry nameiIF4E_HUMAN
AccessioniPrimary (citable) accession number: P06730
Secondary accession number(s): B7Z6V1, D6RCQ6, Q96E95
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: February 1, 1996
Last modified: June 20, 2018
This is version 204 of the entry and version 2 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

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