P06730 (IF4E_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	EIF4E
Synonyms:	EIF4EL1, EIF4F

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	217 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 By similarity. 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. Ref.25
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 or EIF4A2. Interacts with NGDN and PIWIL2. Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1. Interacts directly with CYFIP1 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. Ref.14 Ref.15 Ref.17 Ref.19 Ref.20 Ref.21 Ref.25
Subcellular location	Cytoplasm › P-body Ref.21.
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.9); this was later shown to be wrong (Ref.13).
Mass spectrometry	Molecular mass is 24964.3 Da from positions 2 - 217. Determined by ESI. Ref.26 Molecular mass is 24960 Da from positions 2 - 217. Determined by ESI. Ref.27

Ontologies

Keywords
Biological process	Host-virus interaction Protein biosynthesis Translation regulation
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding
Molecular function	Initiation factor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Inferred from mutant phenotype PubMed 14673156. Source: UniProtKB cytokine-mediated signaling pathway Traceable author statement. Source: Reactome insulin receptor signaling pathway Traceable author statement. Source: Reactome lung development Inferred from electronic annotation. Source: Compara mRNA export from nucleus Traceable author statement. Source: Reactome nuclear-transcribed mRNA poly(A) tail shortening Traceable author statement. Source: Reactome positive regulation of mitotic cell cycle Inferred from mutant phenotype PubMed 14673156. Source: UniProtKB regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	RNA-induced silencing complex Inferred from direct assay Ref.21. Source: MGI cytoplasmic mRNA processing body Inferred from direct assay Ref.21. Source: MGI cytoplasmic stress granule Inferred from direct assay PubMed 21883093. Source: UniProtKB cytosol Traceable author statement. Source: Reactome eukaryotic translation initiation factor 4F complex Traceable author statement Ref.1. Source: ProtInc mRNA cap binding complex Inferred from direct assay Ref.25. Source: UniProtKB
Molecular_function	RNA cap binding Traceable author statement Ref.1. Source: ProtInc translation initiation factor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF4EBP1	Q13541	4	EBI-73440,EBI-74090
EIF4EBP3	O60516	2	EBI-73440,EBI-746950
EIF4ENIF1	Q9NRA8	5	EBI-73440,EBI-301024
EIF4G1	Q04637	2	EBI-73440,EBI-73711
EMX2	Q04743	4	EBI-73440,EBI-399831
GEMIN5	Q8TEQ6	3	EBI-73440,EBI-443630
MKNK1	Q9BUB5	2	EBI-73440,EBI-73837

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P06730-1)

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.

Isoform 2 (identifier: P06730-2)

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

Note: No experimental confirmation available.

Isoform 3 (identifier: P06730-3)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.26

Chain

2 – 217

216

Eukaryotic translation initiation factor 4E

PRO_0000193634

Regions

Region

37 – 40

4

EIF4EBP1/2/3 binding

Region

56 – 57

2

7-methylguanosine-containing mRNA cap binding

Region

73 – 77

5

EIF4EBP1/2/3 binding

Region

102 – 103

2

7-methylguanosine-containing mRNA cap binding

Region

132 – 139

8

EIF4EBP1/2/3 binding

Region

157 – 162

6

7-methylguanosine-containing mRNA cap binding

Region

205 – 207

3

7-methylguanosine-containing mRNA cap binding

Amino acid modifications

Modified residue

209

1

Phosphoserine; by PKC and MKNK2 Ref.12 Ref.13 Ref.18

Natural variations

Alternative sequence

1 – 6

6

MATVEP → MLDLTSRGQVGTSRRMAEAA CSAHFL in isoform 3.

VSP_043591

Alternative sequence

133

1

T → TRWDLAMLPRLVSNFWPQVI LPLQPPKVLELQ in isoform 2.

VSP_042014

Experimental info

Mutagenesis

53

1

S → A or D: No effect on phosphorylation level nor incorporation into eIF4F complex. Ref.10 Ref.11

Mutagenesis

102

1

W → L: Decrease in mRNA cap binding; when associated with A-105. Ref.8

Mutagenesis

103

1

E → A: No effect. Ref.8

Mutagenesis

104

1

D → A: No effect. Ref.8

Mutagenesis

105

1

E → A: Decrease in mRNA cap binding; when associated with L-102. Ref.8

Mutagenesis

119

1

K → A: Higher affinity for EIF4G1. Ref.26

Sequence conflict

127

1

D → N in AAH12611. Ref.5

Secondary structure

1

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217

Helix Strand Turn

Details...

Helix

31 – 33

3

Beta strand

38 – 48

11

Beta strand

52 – 54

3

Helix

57 – 59

3

Beta strand

60 – 68

9

Helix

69 – 78

10

Helix

82 – 84

3

Beta strand

90 – 95

6

Beta strand

100 – 103

4

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

Turn

188 – 192

5

Beta strand

196 – 199

4

Helix

200 – 202

3

Beta strand

206 – 208

3

Beta strand

214 – 216

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 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
	Isoform 2 [UniParc]. Checksum: 3869E3249A241190	FASTA	248	28,778
	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 LETRWDLAML PRLVSNFWPQ VILPLQPPKV LELQLLCLIG ESFDDYSDDV 190 200 210 220 230 240 CGAVVNVRAK GDKIAIWTTE CENREAVTHI GRVYKERLGL PPKIVIGYQS HADTATKSGS TTKNRFVV
	Isoform 3 [UniParc]. Checksum: D4925235C678DE08	FASTA	237	27,260
	10 20 30 40 50 60 MLDLTSRGQV GTSRRMAEAA CSAHFLETTP TPNPPTTEEE KTESNQEVAN PEHYIKHPLQ 70 80 90 100 110 120 NRWALWFFKN DKSKTWQANL RLISKFDTVE DFWALYNHIQ LSSNLMPGCD YSLFKDGIEP 130 140 150 160 170 180 MWEDEKNKRG GRWLITLNKQ QRRSDLDRFW LETLLCLIGE SFDDYSDDVC GAVVNVRAKG 190 200 210 220 230 DKIAIWTTEC ENREAVTHIG 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION TO 108 AND 189.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Small intestine.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Testis.
[6]	"Transcriptome analysis of human gastric cancer." Oh J.H., Yang J.O., Hahn Y., Kim M.R., Byun S.S., Jeon Y.J., Kim J.M., Song K.S., Noh S.M., Kim S., Yoo H.S., Kim Y.S., Kim N.S. Mamm. Genome 16:942-954(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-214 (ISOFORM 2). Tissue: Myeloma.
[7]	"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] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[8]	"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] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TRP-102; GLU-103; ASP-104 AND GLU-105.
[9]	"Phosphorylation site of eukaryotic initiation factor 4E." Rychlik W., Russ M.A., Rhoads R.E. J. Biol. Chem. 262:10434-10437(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[10]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, MUTAGENESIS OF SER-53.
[11]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, MUTAGENESIS OF SER-53.
[12]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-209.
[13]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-209.
[14]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF4G AND EIF4EBP1.
[15]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF4ENIF1. Tissue: Fetal brain and Placenta.
[16]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY MKNK1.
[17]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF4A1 AND EIF4A2.
[18]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-209 BY MKNK2.
[19]	"The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization." Scheper G.C., Parra J.L., Wilson M., Van Kollenburg B., Vertegaal A.C.O., Han Z.-G., Proud C.G. Mol. Cell. Biol. 23:5692-5705(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MKNK2.
[20]	"Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies." Wichroski M.J., Robb G.B., Rana T.M. PLoS Pathog. 2:E41-E41(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APOBEC3G.
[21]	"LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing." James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M., Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J., Longmore G.D., Bushell M., Sharp T.V. Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH LIMD1; WTIP AND AJUBA.
[22]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH MRNA CAP ANALOGS.
[24]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR IN COMPLEX WITH EIF4G3 AND MRNA CAP ANALOGS.
[25]	"Structural basis for mRNA cap-binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods." Tomoo K., Matsushita Y., Fujisaki H., Abiko F., Shen X., Taniguchi T., Miyagawa H., Kitamura K., Miura K., Ishida T. Biochim. Biophys. Acta 1753:191-208(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 27-217 IN COMPLEX WITH MRNA CAP ANALOG AND EIF4EBP1, FUNCTION, INTERACTION WITH EIF4EBP1; EIF4EBP2 AND EIF4EBP3.
[26]	"Cap-free structure of eIF4E suggests a basis for conformational regulation by its ligands." Volpon L., Osborne M.J., Topisirovic I., Siddiqui N., Borden K.L.B. EMBO J. 25:5138-5149(2006) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR, CLEAVAGE OF INITIATOR METHIONINE, MASS SPECTROMETRY, MUTAGENESIS OF LYS-119.
[27]	"Crystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives." Brown C.J., McNae I., Fischer P.M., Walkinshaw M.D. J. Mol. Biol. 372:7-15(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH MRNA CAP ANALOGS, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00027485.
IPI00873680.

PIR

A26411.

RefSeq

NP_001124150.1. NM_001130678.1.
NP_001124151.1. NM_001130679.1.
NP_001959.1. NM_001968.3.

UniGene

Hs.249718.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
2W97	X-ray	2.29	A/B	1-217	[»]
3AM7	X-ray	2.20	A	27-217	[»]
3TF2	X-ray	2.10	A/B/C/D	1-217	[»]
3U7X	X-ray	2.10	A/B	1-217	[»]
4AZA	X-ray	2.16	A/C	1-217	[»]
4DT6	X-ray	2.60	A	1-217	[»]
4DUM	X-ray	2.95	A	1-217	[»]

ProteinModelPortal

P06730.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-22N.

IntAct

P06730. 20 interactions.

MINT

MINT-85626.

STRING

9606.ENSP00000280892.

PTM databases

PhosphoSite

P06730.

Polymorphism databases

DMDM

1352435.

2D gel databases

OGP

P06730.

REPRODUCTION-2DPAGE

IPI00027485.

Proteomic databases

PaxDb

P06730.

PRIDE

P06730.

Protocols and materials databases

DNASU

1977.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000280892; ENSP00000280892; ENSG00000151247.
ENST00000450253; ENSP00000389624; ENSG00000151247.
ENST00000505992; ENSP00000425561; ENSG00000151247.

GeneID

1977.

KEGG

hsa:1977.

UCSC

uc003hue.2. human.

Organism-specific databases

CTD

1977.

GeneCards

GC04M099799.

H-InvDB

HIX0039231.

HGNC

HGNC:3287. EIF4E.

HPA

CAB004077.
CAB016316.

MIM

133440. gene.

neXtProt

NX_P06730.

Orphanet

106. Autism.

PharmGKB

PA27714.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5053.

HOGENOM

HOG000186751.

HOVERGEN

HBG006130.

KO

K03259.

OMA

FWLETRW.

OrthoDB

EOG48GW45.

PhylomeDB

P06730.

Enzyme and pathway databases

Pathway_Interaction_DB

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

Reactome

REACT_111102. Signal Transduction.
REACT_1675. mRNA Processing.
REACT_17015. Metabolism of proteins.
REACT_1762. 3' -UTR-mediated translational regulation.
REACT_21257. Metabolism of RNA.
REACT_6900. Immune System.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P06730.

Bgee

P06730.

CleanEx

HS_EIF4E.

Genevestigator

P06730.

GermOnline

ENSG00000151247. Homo sapiens.

Family and domain databases

Gene3D

3.30.760.10. 1 hit.

InterPro

IPR023398. TIF_eIF4e-like_dom.
IPR001040. TIF_eIF_4E.
IPR019770. TIF_eIF_4E_CS.
[Graphical view]

PANTHER

PTHR11960. PTHR11960. 1 hit.

Pfam

PF01652. IF4E. 1 hit.
[Graphical view]

SUPFAM

SSF55418. TIF_eIF_4E. 1 hit.

PROSITE

PS00813. IF4E. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P06730.

ChEMBL

CHEMBL4848.

ChiTaRS

EIF4E. human.

EvolutionaryTrace

P06730.

GenomeRNAi

1977.

NextBio

7999.

SOURCE

Search...

Entry information

Entry name

IF4E_HUMAN

Accession

Primary (citable) accession number: P06730
Secondary accession number(s): B7Z6V1, D6RCQ6, Q96E95

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 154 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.