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Protein

Eukaryotic translation initiation factor 4E type 2

Gene

EIF4E2

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei110 – 11017-methylguanosine-containing mRNA cap

GO - Molecular functioni

  1. poly(A) RNA binding Source: UniProtKB
  2. RNA cap binding Source: ProtInc
  3. translation factor activity, nucleic acid binding Source: ProtInc
  4. translation initiation factor activity Source: UniProtKB-KW
  5. ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  1. cytokine-mediated signaling pathway Source: Reactome
  2. in utero embryonic development Source: Ensembl
  3. negative regulation of translation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Initiation factor

Keywords - Biological processi

Protein biosynthesis, Translation regulation

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

ReactomeiREACT_115831. ISG15 antiviral mechanism.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:EIF4E2
Synonyms:EIF4EL3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:3293. EIF4E2.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. mRNA cap binding complex Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi63 – 631W → A: Unable to bind capped mRNA. 1 Publication
Mutagenesisi95 – 951W → A: Ability to bind capped mRNA reduced to 40% of wild-type. 1 Publication
Mutagenesisi124 – 1263WED → FAA: Unable to bind capped mRNA. 1 Publication
Mutagenesisi124 – 1241W → A: Ability to bind capped mRNA reduced to less than 10% of wild-type. 1 Publication
Mutagenesisi124 – 1241W → F: Ability to bind capped mRNA reduced to 13% of wild-type. 1 Publication
Mutagenesisi125 – 1251E → A: Ability to bind capped mRNA reduced to less than 10% of wild-type. 1 Publication
Mutagenesisi126 – 1261D → A: Slight reduction in ability to bind capped mRNA. 1 Publication
Mutagenesisi135 – 1351W → A: Unable to bind capped mRNA. 1 Publication
Mutagenesisi148 – 1481W → A: Unable to bind capped mRNA. 1 Publication
Mutagenesisi183 – 1831W → A: Ability to bind capped mRNA reduced to less than 10% of wild-type. 1 Publication
Mutagenesisi183 – 1831W → F: Unable to bind capped mRNA. 1 Publication

Organism-specific databases

PharmGKBiPA27720.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 245245Eukaryotic translation initiation factor 4E type 2PRO_0000193664Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei134 – 1341N6-acetyllysine; alternate1 Publication
Cross-linki134 – 134Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); alternate
Cross-linki222 – 222Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)

Post-translational modificationi

Ubiquitinated by ARIH1, leading to its degradation by the proteasome.1 Publication
ISGylation enhances its cap structure-binding activity and translation-inhibition activity.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

MaxQBiO60573.
PaxDbiO60573.
PRIDEiO60573.

PTM databases

PhosphoSiteiO60573.

Expressioni

Gene expression databases

BgeeiO60573.
CleanExiHS_EIF4E2.
ExpressionAtlasiO60573. baseline and differential.
GenevestigatoriO60573.

Organism-specific databases

HPAiHPA019253.

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 eIF4G. eIF4E is also known to interact with other partners (By similarity). EIF4E2 interacts with EIF4EBP1, EIF4EBP2 and EIF4EBP3 but not with eIF4G.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EIF4ENIF1Q9NRA83EBI-398610,EBI-301024

Protein-protein interaction databases

BioGridi114856. 59 interactions.
DIPiDIP-32578N.
IntActiO60573. 15 interactions.
MINTiMINT-1440115.
STRINGi9606.ENSP00000258416.

Structurei

Secondary structure

1
245
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi55 – 6713Combined sources
Helixi75 – 817Combined sources
Beta strandi82 – 909Combined sources
Helixi91 – 988Combined sources
Helixi104 – 1063Combined sources
Beta strandi109 – 1179Combined sources
Turni127 – 1315Combined sources
Beta strandi133 – 1397Combined sources
Helixi144 – 15613Combined sources
Beta strandi166 – 1738Combined sources
Beta strandi178 – 1858Combined sources
Helixi190 – 20314Combined sources
Beta strandi212 – 2165Combined sources
Helixi217 – 2226Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JGBX-ray1.70A45-234[»]
2JGCX-ray2.40A45-234[»]
ProteinModelPortaliO60573.
SMRiO60573. Positions 45-234.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60573.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni54 – 574EIF4EBP1/2/3 binding
Regioni78 – 7927-methylguanosine-containing mRNA cap bindingBy similarity
Regioni95 – 995EIF4EBP1/2/3 binding
Regioni124 – 12527-methylguanosine-containing mRNA cap binding
Regioni150 – 1578EIF4EBP1/2/3 binding
Regioni174 – 17967-methylguanosine-containing mRNA cap binding
Regioni222 – 22437-methylguanosine-containing mRNA cap bindingBy similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG5053.
GeneTreeiENSGT00520000055549.
HOGENOMiHOG000186751.
HOVERGENiHBG107087.
InParanoidiO60573.
KOiK03259.
OMAiRNTDVFM.
OrthoDBiEOG7GQXWN.
PhylomeDBiO60573.
TreeFamiTF101529.

Family and domain databases

Gene3Di3.30.760.10. 1 hit.
InterProiIPR023398. TIF_eIF4e-like_dom.
IPR001040. TIF_eIF_4E.
IPR019770. TIF_eIF_4E_CS.
[Graphical view]
PANTHERiPTHR11960. PTHR11960. 1 hit.
PfamiPF01652. IF4E. 1 hit.
[Graphical view]
SUPFAMiSSF55418. SSF55418. 1 hit.
PROSITEiPS00813. IF4E. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60573-1) [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
MNNKFDALKD DDSGDHDQNE ENSTQKDGEK EKTERDKNQS SSKRKAVVPG
60 70 80 90 100
PAEHPLQYNY TFWYSRRTPG RPTSSQSYEQ NIKQIGTFAS VEQFWRFYSH
110 120 130 140 150
MVRPGDLTGH SDFHLFKEGI KPMWEDDANK NGGKWIIRLR KGLASRCWEN
160 170 180 190 200
LILAMLGEQF MVGEEICGAV VSVRFQEDII SIWNKTASDQ ATTARIRDTL
210 220 230 240
RRVLNLPPNT IMEYKTHTDS IKMPGRLGPQ RLLFQNLWKP RLNVP
Length:245
Mass (Da):28,362
Last modified:July 31, 1998 - v1
Checksum:i3D3075BFA48B3C12
GO
Isoform 2 (identifier: O60573-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     223-234: MPGRLGPQRLLF → DNSSFRNTKITL
     235-245: Missing.

Note: No experimental confirmation available.

Show »
Length:234
Mass (Da):27,026
Checksum:iC63065135BA86C68
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1 – 2727MNNKF…STQKD → MMTVGTMIRMKKTAHRKI in AAC39871 (PubMed:9653160).CuratedAdd
BLAST

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei223 – 23412MPGRL…QRLLF → DNSSFRNTKITL in isoform 2. CuratedVSP_054783Add
BLAST
Alternative sequencei235 – 24511Missing in isoform 2. CuratedVSP_054784Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2496.1. [O60573-1]
CCDS63159.1. [O60573-2]
RefSeqiNP_001263265.1. NM_001276336.1. [O60573-2]
NP_004837.1. NM_004846.3. [O60573-1]
UniGeneiHs.292026.

Genome annotation databases

EnsembliENST00000258416; ENSP00000258416; ENSG00000135930. [O60573-1]
ENST00000409098; ENSP00000386996; ENSG00000135930. [O60573-2]
GeneIDi9470.
KEGGihsa:9470.
UCSCiuc002vta.3. human. [O60573-1]
uc002vtb.1. human.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2496.1. [O60573-1]
CCDS63159.1. [O60573-2]
RefSeqiNP_001263265.1. NM_001276336.1. [O60573-2]
NP_004837.1. NM_004846.3. [O60573-1]
UniGeneiHs.292026.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JGBX-ray1.70A45-234[»]
2JGCX-ray2.40A45-234[»]
ProteinModelPortaliO60573.
SMRiO60573. Positions 45-234.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114856. 59 interactions.
DIPiDIP-32578N.
IntActiO60573. 15 interactions.
MINTiMINT-1440115.
STRINGi9606.ENSP00000258416.

PTM databases

PhosphoSiteiO60573.

Proteomic databases

MaxQBiO60573.
PaxDbiO60573.
PRIDEiO60573.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000258416; ENSP00000258416; ENSG00000135930. [O60573-1]
ENST00000409098; ENSP00000386996; ENSG00000135930. [O60573-2]
GeneIDi9470.
KEGGihsa:9470.
UCSCiuc002vta.3. human. [O60573-1]
uc002vtb.1. human.

Organism-specific databases

CTDi9470.
GeneCardsiGC02P233414.
HGNCiHGNC:3293. EIF4E2.
HPAiHPA019253.
MIMi605895. gene.
neXtProtiNX_O60573.
PharmGKBiPA27720.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5053.
GeneTreeiENSGT00520000055549.
HOGENOMiHOG000186751.
HOVERGENiHBG107087.
InParanoidiO60573.
KOiK03259.
OMAiRNTDVFM.
OrthoDBiEOG7GQXWN.
PhylomeDBiO60573.
TreeFamiTF101529.

Enzyme and pathway databases

ReactomeiREACT_115831. ISG15 antiviral mechanism.

Miscellaneous databases

ChiTaRSiEIF4E2. human.
EvolutionaryTraceiO60573.
GeneWikiiEIF4E2.
GenomeRNAii9470.
NextBioi35481795.
PROiO60573.
SOURCEiSearch...

Gene expression databases

BgeeiO60573.
CleanExiHS_EIF4E2.
ExpressionAtlasiO60573. baseline and differential.
GenevestigatoriO60573.

Family and domain databases

Gene3Di3.30.760.10. 1 hit.
InterProiIPR023398. TIF_eIF4e-like_dom.
IPR001040. TIF_eIF_4E.
IPR019770. TIF_eIF_4E_CS.
[Graphical view]
PANTHERiPTHR11960. PTHR11960. 1 hit.
PfamiPF01652. IF4E. 1 hit.
[Graphical view]
SUPFAMiSSF55418. SSF55418. 1 hit.
PROSITEiPS00813. IF4E. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1997) [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(2003) [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(1997) [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.
    , 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(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. 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(2003) [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(2002) [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(2006) [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(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-134, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. 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(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 45-234 IN COMPLEX WITH MRNA CAP ANALOGS AND EIF4EBP1.

Entry informationi

Entry nameiIF4E2_HUMAN
AccessioniPrimary (citable) accession number: O60573
Secondary accession number(s): B8ZZJ9, O75349
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 10, 2003
Last sequence update: July 31, 1998
Last modified: February 3, 2015
This is version 133 of the entry and version 1 of the sequence. [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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

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 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.