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Reviewed, UniProtKB/Swiss-Prot P06730 (IF4E_HUMAN)

Last modified February 9, 2010. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Eukaryotic translation initiation factor 4E
      Short name=eIF-4E
      Short name=eIF4E
Alternative name(s):
    mRNA cap-binding protein
    eIF-4F 25 kDa subunit
Gene names
Name: EIF4E
Synonyms: EIF4EL1, EIF4F
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length217 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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.

Subunit structure

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. Nonphosphorylated 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. Rapamycin can attenuate insulin stimulation, mediated by FKBPs. Interacts mutually exclusive with EIF4A1 and EIF4A2. Interacts with NGDN and PIWIL2 By similarity. Interacts with Lassa virus Z protein. Ref.11 Ref.12 Ref.14

Post-translational modification

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

Sequence similarities

Belongs to the eukaryotic initiation factor 4E family.

Caution

Was originally thought to be phosphorylated on Ser-53 (Ref.6); this was later shown to be wrong (Ref.10).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 217216Eukaryotic translation initiation factor 4E
PRO_0000193634

Amino acid modifications

Modified residue21N-acetylalanine Ref.17
Modified residue2091Phosphoserine; by PKC Ref.9 Ref.10

Experimental info

Mutagenesis531S → A or D: No effect on phosphorylation level nor incorporation into eIF4F complex. Ref.7 Ref.8
Mutagenesis1021W → L: Decrease in binding; when associated with A-105. Ref.5
Mutagenesis1031E → A: No effect. Ref.5
Mutagenesis1041D → A: No effect. Ref.5
Mutagenesis1051E → A: Decrease in binding; when associated with A-105. Ref.5
Sequence conflict1271D → N in AAH12611. Ref.3

Secondary structure

................................. 217
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P06730-1 [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: B869B8DE615E699D

FASTA21725,097
        10         20         30         40         50         60 
MATVEPETTP TPNPPTTEEE KTESNQEVAN PEHYIKHPLQ NRWALWFFKN DKSKTWQANL 

        70         80         90        100        110        120 
RLISKFDTVE DFWALYNHIQ LSSNLMPGCD YSLFKDGIEP MWEDEKNKRG GRWLITLNKQ 

       130        140        150        160        170        180 
QRRSDLDRFW LETLLCLIGE SFDDYSDDVC GAVVNVRAKG DKIAIWTTEC ENREAVTHIG 

       190        200        210 
RVYKERLGLP PKIVIGYQSH ADTATKSGST TKNRFVV 

« Hide

References

« Hide 'large scale' references
[1]"Amino acid sequence of the mRNA cap-binding protein from human tissues."
Rychlik W., Domier L.L., Gardner P.R., Hellmann G.M., Rhoads R.E.
Proc. Natl. Acad. Sci. U.S.A. 84:945-949(1987) [PubMed: 3469651] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[2]Erratum
Rychlik W., Domier L.L., Gardner P.R., Hellmann G.M., Rhoads R.E.
Proc. Natl. Acad. Sci. U.S.A. 89:1148-1148(1992) [PubMed: 1736299] [Abstract]
Cited for: SEQUENCE REVISION TO 108 AND 189.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain and Testis.
[4]"Phosphorylation of the proto-oncogene product eukaryotic initiation factor 4E is a common cellular response to tumor necrosis factor."
Marino M.W., Feld L.J., Jaffe E.A., Pfeffer L.M., Han Y.-M., Donner D.B.
J. Biol. Chem. 266:2685-2688(1991) [PubMed: 1993647] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
[5]"Combination of Trp and Glu residues for recognition of mRNA cap structure. Analysis of m7G base recognition site of human cap binding protein (IF-4E) by site-directed mutagenesis."
Ueda H., Iyo H., Doi M., Inoue M., Ishida T., Morioka H., Tanaka T., Nishikawa S., Uesugi S.
FEBS Lett. 280:207-210(1991) [PubMed: 1672854] [Abstract]
Cited for: MUTAGENESIS OF TRP-102; GLU-103; ASP-104 AND GLU-105.
[6]"Phosphorylation site of eukaryotic initiation factor 4E."
Rychlik W., Russ M.A., Rhoads R.E.
J. Biol. Chem. 262:10434-10437(1987) [PubMed: 3112145] [Abstract]
Cited for: PHOSPHORYLATION.
[7]"Characterization of wild-type and Ser53 mutant eukaryotic initiation factor 4E overexpression in mammalian cells."
Kaufman R.J., Murtha-Riel P., Pittman D.D., Davies M.V.
J. Biol. Chem. 268:11902-11909(1993) [PubMed: 8505316] [Abstract]
Cited for: PHOSPHORYLATION, MUTAGENESIS OF SER-53.
[8]"Role of Ser-53 phosphorylation in the activity of human translation initiation factor eIF-4E in mammalian and yeast cells."
Zhang Y., Klein H.L., Schneider R.J.
Gene 163:283-288(1995) [PubMed: 7590282] [Abstract]
Cited for: PHOSPHORYLATION, MUTAGENESIS OF SER-53.
[9]"Phosphorylation of eukaryotic protein synthesis initiation factor 4E at Ser-209."
Joshi B., Cai A.L., Keiper B.D., Minich W.B., Mendez R., Beach C.M., Stepinski J., Stolarski R., Darzynkiewicz E., Rhoads R.E.
J. Biol. Chem. 270:14597-14603(1995) [PubMed: 7782323] [Abstract]
Cited for: PHOSPHORYLATION AT SER-209.
[10]"Serine 209, not serine 53, is the major site of phosphorylation in initiation factor eIF-4E in serum-treated Chinese hamster ovary cells."
Flynn A., Proud C.G.
J. Biol. Chem. 270:21684-21688(1995) [PubMed: 7665584] [Abstract]
Cited for: PHOSPHORYLATION AT SER-209.
[11]"Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E."
Haghighat A., Mader S., Pause A., Sonenberg N.
EMBO J. 14:5701-5709(1995) [PubMed: 8521827] [Abstract]
Cited for: INTERACTION WITH EIF4G AND EIF4EBP1.
[12]"A novel shuttling protein, 4E-T, mediates the nuclear import of the mRNA 5' cap-binding protein, eIF4E."
Dostie J., Ferraiuolo M., Pause A., Adam S.A., Sonenberg N.
EMBO J. 19:3142-3156(2000) [PubMed: 10856257] [Abstract]
Cited for: INTERACTION WITH EIF4ENIF1.
Tissue: Fetal brain and Placenta.
[13]"Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E."
Pyronnet S., Imataka H., Gingras A.-C., Fukunaga R., Hunter T., Sonenberg N.
EMBO J. 18:270-279(1999) [PubMed: 9878069] [Abstract]
Cited for: PHOSPHORYLATION BY MKNK1.
[14]"Eukaryotic initiation factors 4A (eIF4A) and 4G (eIF4G) mutually interact in a 1:1 ratio in vivo."
Li W., Belsham G.J., Proud C.G.
J. Biol. Chem. 276:29111-29115(2001) [PubMed: 11408474] [Abstract]
Cited for: INTERACTION WITH EIF4A1 AND EIF4A2.
[15]"The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells."
Scheper G.C., Morrice N.A., Kleijn M., Proud C.G.
Mol. Cell. Biol. 21:743-754(2001) [PubMed: 11154262] [Abstract]
Cited for: PHOSPHORYLATION BY MKNK2.
[16]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[17]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY.
[18]"Crystal structures of 7-methylguanosine 5'-triphosphate (m(7)GTP)- and P(1)-7-methylguanosine-P(3)-adenosine-5',5'-triphosphate (m(7)GpppA)-bound human full-length eukaryotic initiation factor 4E: biological importance of the C-terminal flexible region."
Tomoo K., Shen X., Okabe K., Nozoe Y., Fukuhara S., Morino S., Ishida T., Taniguchi T., Hasegawa H., Terashima A., Sasaki M., Katsuya Y., Kitamura K., Miyoshi H., Ishikawa M., Miura K.
Biochem. J. 362:539-544(2002) [PubMed: 11879179] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[19]"Backbone resonance assignment of human eukaryotic translation initiation factor 4E (eIF4E) in complex with 7-methylguanosine diphosphate (m7GDP) and a 17-amino acid peptide derived from human eIF4GII."
Miura T., Shiratori Y., Shimma N.
J. Biomol. NMR 27:279-280(2003) [PubMed: 12975586] [Abstract]
Cited for: STRUCTURE BY NMR IN COMPLEX WITH EIF4G3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M15353 mRNA. Translation: AAC13647.1.
BC012611 mRNA. Translation: AAH12611.1.
BC035166 mRNA. Translation: AAH35166.1.
BC043226 mRNA. Translation: AAH43226.1.
IPIIPI00027485.
PIRA26411.
RefSeqNP_001959.1.
UniGeneHs.249718

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-22N.
IntActP06730. 20 interactions.
STRINGP06730.

PTM databases

PhosphoSiteP06730.

2-D gel databases

OGPP06730.
REPRODUCTION-2DPAGEIPI00027485.

Proteomic databases

PRIDEP06730.

Genome annotation databases

EnsemblENST00000450253; ENSP00000389624; ENSG00000151247; Homo sapiens. [Genome view]
GeneID1977.
NMPDRfig|9606.3.peg.24449.
UCSCuc003hue.1. human.

Organism-specific databases

CTD1977.
GeneCardsGC04M100046.
GC17M044855.
H-InvDBHIX0004392.
HIX0039231.
HGNCHGNC:3287. EIF4E.
HPACAB004077.
CAB016316.
MIM133440. gene.
PharmGKBPA27714.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG19373.
HOVERGENP06730.
OrthoDBEOG98WFMZ.
PhylomeDBP06730.

Enzyme and pathway databases

Pathway_Interaction_DBmtor_4pathway. mTOR signaling pathway.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.
ReactomeREACT_125. Processing of Capped Intron-Containing Pre-mRNA.
REACT_17015. Metabolism of proteins.
REACT_1762. 3' -UTR-mediated translational regulation.
REACT_20605. Metabolism of mRNA.
REACT_498. Signaling by Insulin receptor.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressP06730.
BgeeP06730.
CleanExHS_EIF4E.
GenevestigatorP06730.
GermOnlineENSG00000151247. Homo sapiens.

Family and domain databases

InterProIPR001040. TIF_eIF_4E.
IPR019770. TIF_eIF_4E_CS.
[Graphical view]
Gene3DG3DSA:3.30.760.10. TIF_eIF_4E. 1 hit.
PANTHERPTHR11960. TIF_eIF_4E. 1 hit.
PfamPF01652. IF4E. 1 hit.
[Graphical view]
PROSITEPS00813. IF4E. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio7999.
SOURCESearch...

Entry information

Entry nameIF4E_HUMAN
AccessionPrimary (citable) accession number: P06730
Secondary accession number(s): Q96E95
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: February 1, 1996
Last modified: February 9, 2010
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

Relevant documents

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Translation initiation factors

List of translation initiation factor entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents