Reviewed, UniProtKB/Swiss-Prot P06730 (IF4E_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	217 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.
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).

Ontologies

Keywords
Biological process	Host-virus interaction Protein biosynthesis Translation regulation
Ligand	RNA-binding
Molecular function	Initiation factor
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW translational initiation Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from Experiment. Source: Reactome eukaryotic translation initiation factor 4F complex Ref.1 Traceable author statement. Source: ProtInc
Molecular function	RNA cap binding Ref.1 Traceable author statement. Source: ProtInc protein binding Ref.12 Ref.13 Inferred from physical interaction. Source: IntAct translation initiation factor activity Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CYFIP1	Q7L576	1	EBI-73440,EBI-1048143
EIF4A1	P60842	1	EBI-73440,EBI-73449
EIF4A2	Q14240	1	EBI-73440,EBI-73473
EIF4EBP1	Q13541	4	EBI-73440,EBI-74090
EIF4EBP2	Q13542	1	EBI-73440,EBI-935137
EIF4EBP3	O60516	2	EBI-73440,EBI-746950
EIF4ENIF1	Q9NRA8	1	EBI-73440,EBI-301024
EIF4G1	Q04637	1	EBI-73440,EBI-73711
EMX2	Q04743	2	EBI-73440,EBI-399831
GEMIN5	Q8TEQ6	1	EBI-73440,EBI-443630
MKNK1	Q9BUB5	1	EBI-73440,EBI-73837

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 217

217

Eukaryotic translation initiation factor 4E

PRO_0000193634

Amino acid modifications

Modified residue

209

1

Phosphoserine; by PKC Ref.9 Ref.10

Experimental info

Mutagenesis

53

1

S → A or D: No effect on phosphorylation level nor incorporation into eIF4F complex. Ref.7 Ref.8

Mutagenesis

102

1

W → L: Decrease in binding; when associated with A-105. Ref.5

Mutagenesis

103

1

E → A: No effect. Ref.5

Mutagenesis

104

1

D → A: No effect. Ref.5

Mutagenesis

105

1

E → A: Decrease in binding; when associated with A-105. Ref.5

Sequence conflict

127

1

D → N in AAH12611. Ref.3

Secondary structure

1

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217

Helix Strand Turn

Details...

Helix

31 – 33

3

Beta strand

38 – 48

11

Helix

57 – 59

3

Beta strand

60 – 68

9

Helix

69 – 78

10

Helix

82 – 84

3

Beta strand

90 – 95

6

Turn

105 – 109

5

Beta strand

111 – 116

6

Helix

121 – 124

4

Helix

126 – 138

13

Turn

139 – 142

4

Helix

143 – 148

6

Beta strand

149 – 155

7

Beta strand

162 – 168

7

Helix

173 – 187

15

Beta strand

196 – 199

4

Helix

200 – 202

3

Beta strand

214 – 216

3

Sequences

	Sequence		Length	Mass (Da)
	P06730-1 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: B869B8DE615E699D	FASTA	217	25,097
	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

References

	« Hide 'large scale' referencesShow '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]	"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).
[18]	"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

EMBLGenBankDDBJ

M15353 mRNA. Translation: AAC13647.1.
BC012611 mRNA. Translation: AAH12611.1.
BC035166 mRNA. Translation: AAH35166.1.
BC043226 mRNA. Translation: AAH43226.1.

IPI

IPI00027485.

PIR

A26411.

RefSeq

NP_001959.1.

UniGene

Hs.249718

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IPB	X-ray	2.00	A	1-217	[»]
1IPC	X-ray	2.00	A	1-217	[»]
1WKW	X-ray	2.10	A	27-217	[»]
2GPQ	NMR	-	A	1-217	[»]
2V8W	X-ray	2.30	A/E	1-217	[»]
2V8X	X-ray	2.30	A/E	1-217	[»]
2V8Y	X-ray	2.10	A/E	1-217	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:22N.

IntAct

P06730. 20 interactions.

PTM databases

PhosphoSite

P06730.

2-D gel databases

OGP

P06730.

REPRODUCTION-2DPAGE

IPI00027485.

Proteomic databases

PRIDE

P06730.

Genome annotation databases

Ensembl

ENSG00000151247. Homo sapiens. [Contig view]

GeneID

1977.

NMPDR

fig|9606.3.peg.24449.

Organism-specific databases

GeneCards

GC04M100046.
GC17M044855.

H-InvDB

HIX0004392.
HIX0039231.

HGNC

HGNC:3287. EIF4E.

HPA

CAB004077.
CAB016316.

MIM

133440. gene.

PharmGKB

PA27714.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P06730.

HOVERGEN

P06730.

Enzyme and pathway databases

Pathway_Interaction_DB

mtor_4pathway. mTOR signaling pathway.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.

Reactome

REACT_1675. mRNA Processing.
REACT_1762. 3' -UTR-mediated translational regulation.
REACT_498. Signaling by Insulin receptor.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P06730.

Bgee

P06730.

CleanEx

HS_EIF4E.

GermOnline

ENSG00000151247. Homo sapiens.

Family and domain databases

InterPro

IPR001040. TIF_eIF_4E.
IPR019770. TIF_eIF_4E_CS.
[Graphical view]

Gene3D

G3DSA:3.30.760.10. TIF_eIF_4E. 1 hit.

PANTHER

PTHR11960. TIF_eIF_4E. 1 hit.

Pfam

PF01652. IF4E. 1 hit.
[Graphical view]

ProDom

PD003697. TIF_eIF_4E. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS00813. IF4E. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

7999.

SOURCE

Search...

Entry information

Entry name

IF4E_HUMAN

Accession

Primary (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:	June 16, 2009
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)