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UniProtKB - P06730 (IF4E_HUMAN)

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Protein

Eukaryotic translation initiation factor 4E

Gene

EIF4E

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:3287. EIF4E.

Subcellular locationi

GO - Cellular componenti

  • chromatoid body Source: Ensembl
  • cytoplasm Source: AgBase
  • cytoplasmic stress granule Source: UniProtKB
  • cytosol Source: UniProtKB
  • eukaryotic translation initiation factor 4F complex Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • mRNA cap binding complex Source: UniProtKB
  • P-body Source: HPA
  • perinuclear region of cytoplasm Source: AgBase
  • RISC complex Source: MGI
Complete GO annotation...

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.
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). Interacts with Lassa virus Z protein. 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).By similarity14 Publications

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
Complete GO annotation...

Protein-protein interaction databases

BioGridi108292. 50 interactors.
DIPiDIP-22N.
IntActiP06730. 35 interactors.
MINTiMINT-85626.

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

Belongs to the eukaryotic initiation factor 4E family.Curated

Phylogenomic databases

GeneTreeiENSGT00520000055549.
HOGENOMiHOG000186751.
HOVERGENiHBG006130.
InParanoidiP06730.
KOiK03259.
OMAiHLFKHPL.
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

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.

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 7, 2017
This is version 196 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

Caution

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

Keywords - Technical termi

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

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Translation initiation factors
    List of translation initiation factor entries
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families