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O60573 (IF4E2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Eukaryotic translation initiation factor 4E type 2

Short name=eIF-4E type 2
Short name=eIF4E type 2
Alternative name(s):
Eukaryotic translation initiation factor 4E homologous protein
Eukaryotic translation initiation factor 4E-like 3
eIF4E-like protein 4E-LP
mRNA cap-binding protein 4EHP
mRNA cap-binding protein type 3
Gene names
Name:EIF4E2
Synonyms:EIF4EL3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length245 AA.
Sequence statusComplete.
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 eIF4G. eIF4E is also known to interact with other partners By similarity. EIF4E2 interacts with EIF4EBP1, EIF4EBP2 and EIF4EBP3 but not with eIF4G. Ref.2

Post-translational modification

Ubiquitinated by ARIH1, leading to its degradation by the proteasome. Ref.7

ISGylation enhances its cap structure-binding activity and translation-inhibition activity. Ref.8

Sequence similarities

Belongs to the eukaryotic initiation factor 4E family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

EIF4ENIF1Q9NRA83EBI-398610,EBI-301024

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60573-1)

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: O60573-2)

The sequence of this isoform differs from the canonical sequence as follows:
     223-234: MPGRLGPQRLLF → DNSSFRNTKITL
     235-245: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 245245Eukaryotic translation initiation factor 4E type 2
PRO_0000193664

Regions

Region54 – 574EIF4EBP1/2/3 binding
Region78 – 7927-methylguanosine-containing mRNA cap binding By similarity
Region95 – 995EIF4EBP1/2/3 binding
Region124 – 12527-methylguanosine-containing mRNA cap binding
Region150 – 1578EIF4EBP1/2/3 binding
Region174 – 17967-methylguanosine-containing mRNA cap binding
Region222 – 22437-methylguanosine-containing mRNA cap binding By similarity

Sites

Binding site11017-methylguanosine-containing mRNA cap

Amino acid modifications

Modified residue1341N6-acetyllysine; alternate Ref.9
Cross-link134Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); alternate Ref.8
Cross-link222Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.8

Natural variations

Alternative sequence223 – 23412MPGRL…QRLLF → DNSSFRNTKITL in isoform 2.
VSP_054783
Alternative sequence235 – 24511Missing in isoform 2.
VSP_054784

Experimental info

Mutagenesis631W → A: Unable to bind capped mRNA.
Mutagenesis951W → A: Ability to bind capped mRNA reduced to 40% of wild-type.
Mutagenesis124 – 1263WED → FAA: Unable to bind capped mRNA.
Mutagenesis1241W → A: Ability to bind capped mRNA reduced to less than 10% of wild-type.
Mutagenesis1241W → F: Ability to bind capped mRNA reduced to 13% of wild-type.
Mutagenesis1251E → A: Ability to bind capped mRNA reduced to less than 10% of wild-type.
Mutagenesis1261D → A: Slight reduction in ability to bind capped mRNA.
Mutagenesis1351W → A: Unable to bind capped mRNA.
Mutagenesis1481W → A: Unable to bind capped mRNA.
Mutagenesis1831W → A: Ability to bind capped mRNA reduced to less than 10% of wild-type.
Mutagenesis1831W → F: Unable to bind capped mRNA.
Sequence conflict1 – 2727MNNKF…STQKD → MMTVGTMIRMKKTAHRKI in AAC39871. Ref.3

Secondary structure

.......................... 245
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 3D3075BFA48B3C12

FASTA24528,362
        10         20         30         40         50         60 
MNNKFDALKD DDSGDHDQNE ENSTQKDGEK EKTERDKNQS SSKRKAVVPG PAEHPLQYNY 

        70         80         90        100        110        120 
TFWYSRRTPG RPTSSQSYEQ NIKQIGTFAS VEQFWRFYSH MVRPGDLTGH SDFHLFKEGI 

       130        140        150        160        170        180 
KPMWEDDANK NGGKWIIRLR KGLASRCWEN LILAMLGEQF MVGEEICGAV VSVRFQEDII 

       190        200        210        220        230        240 
SIWNKTASDQ ATTARIRDTL RRVLNLPPNT IMEYKTHTDS IKMPGRLGPQ RLLFQNLWKP 


RLNVP 

« Hide

Isoform 2 [UniParc].

Checksum: C63065135BA86C68
Show »

FASTA23427,026

References

« Hide 'large scale' references
[1]"Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap-binding protein."
Rom E., Kim H.C., Gingras A.-C., Marcotrigiano J., Favre D., Olsen H., Burley S.K., Sonenberg N.
J. Biol. Chem. 273:13104-13109(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, 3D-STRUCTURE MODELING, MUTAGENESIS.
Tissue: Follicular cell.
[2]"Characterization of mammalian eIF4E-family members."
Joshi B., Cameron A., Jagus R.
Eur. J. Biochem. 271:2189-2203(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH EIF4EBP1; EIF4EBP2 AND EIF4EBP3.
Tissue: Mammary gland.
[3]"Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning."
Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H., He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H., Wang Y.-X., Chen S.-J., Chen Z.
Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Umbilical cord blood.
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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: Muscle, Urinary bladder and Uterus.
[7]"Human homologue of ariadne promotes the ubiquitylation of translation initiation factor 4E homologous protein, 4EHP."
Tan N.G., Ardley H.C., Scott G.B., Rose S.A., Markham A.F., Robinson P.A.
FEBS Lett. 554:501-504(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY ARIH1.
[8]"ISG15 modification of the eIF4E cognate 4EHP enhances cap structure-binding activity of 4EHP."
Okumura F., Zou W., Zhang D.E.
Genes Dev. 21:255-260(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION AT LYS-134 AND LYS-222.
[9]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-134, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"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].
[11]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP-bound and unliganded forms."
Rosettani P., Knapp S., Vismara M.-G., Rusconi L., Cameron A.D.
J. Mol. Biol. 368:691-705(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 45-234 IN COMPLEX WITH MRNA CAP ANALOGS AND EIF4EBP1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF047695 mRNA. Translation: AAC18565.1.
AF068117 mRNA. Translation: AAC19374.1.
AF038957 mRNA. Translation: AAC39871.1.
AC073254 Genomic DNA. No translation available.
AC092165 Genomic DNA. No translation available.
AC093383 Genomic DNA. No translation available.
CH471063 Genomic DNA. Translation: EAW71008.1.
BC005392 mRNA. Translation: AAH05392.1.
BC005874 mRNA. Translation: AAH05874.1.
BC021226 mRNA. Translation: AAH21226.1.
BC021690 mRNA. Translation: AAH21690.1.
CCDSCCDS2496.1.
RefSeqNP_001263265.1. NM_001276336.1. [O60573-2]
NP_004837.1. NM_004846.3. [O60573-1]
UniGeneHs.292026.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JGBX-ray1.70A45-234[»]
2JGCX-ray2.40A45-234[»]
ProteinModelPortalO60573.
SMRO60573. Positions 45-234.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114856. 21 interactions.
DIPDIP-32578N.
IntActO60573. 15 interactions.
MINTMINT-1440115.
STRING9606.ENSP00000258416.

PTM databases

PhosphoSiteO60573.

Proteomic databases

MaxQBO60573.
PaxDbO60573.
PRIDEO60573.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000258416; ENSP00000258416; ENSG00000135930.
ENST00000409098; ENSP00000386996; ENSG00000135930.
GeneID9470.
KEGGhsa:9470.
UCSCuc002vta.3. human. [O60573-1]

Organism-specific databases

CTD9470.
GeneCardsGC02P233414.
HGNCHGNC:3293. EIF4E2.
HPAHPA019253.
MIM605895. gene.
neXtProtNX_O60573.
PharmGKBPA27720.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5053.
HOGENOMHOG000186751.
HOVERGENHBG107087.
InParanoidO60573.
KOK03259.
OMADSIKAWE.
OrthoDBEOG7GQXWN.
PhylomeDBO60573.
TreeFamTF101529.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressO60573.
BgeeO60573.
CleanExHS_EIF4E2.
GenevestigatorO60573.

Family and domain databases

Gene3D3.30.760.10. 1 hit.
InterProIPR023398. TIF_eIF4e-like_dom.
IPR001040. TIF_eIF_4E.
IPR019770. TIF_eIF_4E_CS.
[Graphical view]
PANTHERPTHR11960. PTHR11960. 1 hit.
PfamPF01652. IF4E. 1 hit.
[Graphical view]
SUPFAMSSF55418. SSF55418. 1 hit.
PROSITEPS00813. IF4E. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSEIF4E2. human.
EvolutionaryTraceO60573.
GeneWikiEIF4E2.
GenomeRNAi9470.
NextBio35481795.
PROO60573.
SOURCESearch...

Entry information

Entry nameIF4E2_HUMAN
AccessionPrimary (citable) accession number: O60573
Secondary accession number(s): B8ZZJ9, O75349
Entry history
Integrated into UniProtKB/Swiss-Prot: April 11, 2003
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM