Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1107-methylguanosine-containing mRNA cap1

GO - Molecular functioni

  • poly(A) RNA binding Source: UniProtKB
  • RNA cap binding Source: ProtInc
  • translation factor activity, RNA binding Source: ProtInc
  • translation initiation factor activity Source: UniProtKB-KW
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • in utero embryonic development Source: Ensembl
  • 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

BioCyciZFISH:ENSG00000135930-MONOMER.
ReactomeiR-HSA-1169408. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:3293. EIF4E2.

Subcellular locationi

GO - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi63W → A: Unable to bind capped mRNA. 1 Publication1
Mutagenesisi95W → A: Ability to bind capped mRNA reduced to 40% of wild-type. 1 Publication1
Mutagenesisi121K → R: Does not affect ubiquitination by ARIH1; when associated with R-130; R-134 and R-222. 1 Publication1
Mutagenesisi124 – 126WED → FAA: Unable to bind capped mRNA. 1 Publication3
Mutagenesisi124W → A: Ability to bind capped mRNA reduced to less than 10% of wild-type. 1 Publication1
Mutagenesisi124W → F: Ability to bind capped mRNA reduced to 13% of wild-type. 1 Publication1
Mutagenesisi125E → A: Ability to bind capped mRNA reduced to less than 10% of wild-type. 1 Publication1
Mutagenesisi126D → A: Slight reduction in ability to bind capped mRNA. 1 Publication1
Mutagenesisi130K → R: Does not affect ubiquitination by ARIH1; when associated with R-121; R-134 and R-222. 1 Publication1
Mutagenesisi134K → R: Does not affect ubiquitination by ARIH1; when associated with R-121; R-130 and R-222. 1 Publication1
Mutagenesisi135W → A: Unable to bind capped mRNA. 1 Publication1
Mutagenesisi148W → A: Unable to bind capped mRNA. 1 Publication1
Mutagenesisi183W → A: Ability to bind capped mRNA reduced to less than 10% of wild-type. 1 Publication1
Mutagenesisi183W → F: Unable to bind capped mRNA. 1 Publication1
Mutagenesisi222K → R: Does not affect ubiquitination by ARIH1; when associated with R-121; R-130 and R-134. 1 Publication1

Organism-specific databases

DisGeNETi9470.
OpenTargetsiENSG00000135930.
PharmGKBiPA27720.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001936641 – 245Eukaryotic translation initiation factor 4E type 2Add BLAST245

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13PhosphoserineCombined sources1
Modified residuei134N6-acetyllysine; alternateCombined sources1
Cross-linki134Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); alternate1 Publication
Cross-linki222Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)1 Publication

Post-translational modificationi

Ubiquitinated by ARIH1 (PubMed:14623119, PubMed:25624349). The consequences of ubiquitination are however unclear: according to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest (PubMed:25624349). According to another report ubiquitination leads to its subsequent degradation (PubMed:14623119).2 Publications
ISGylation enhances its cap structure-binding activity and translation-inhibition activity.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO60573.
PaxDbiO60573.
PeptideAtlasiO60573.
PRIDEiO60573.

PTM databases

iPTMnetiO60573.
PhosphoSitePlusiO60573.

Expressioni

Gene expression databases

BgeeiENSG00000135930.
CleanExiHS_EIF4E2.
ExpressionAtlasiO60573. baseline and differential.
GenevisibleiO60573. HS.

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
ADAMTSL4Q6UY14-33EBI-398610,EBI-10173507
AESQ081173EBI-398610,EBI-717810
AMOTL2Q9Y2J4-43EBI-398610,EBI-10187270
CARD9Q9H2573EBI-398610,EBI-751319
CDR2Q018503EBI-398610,EBI-1181367
EIF4ENIF1Q9NRA83EBI-398610,EBI-301024
HOMEZQ8IX15-33EBI-398610,EBI-10172004
KRT13A1A4E93EBI-398610,EBI-10171552
KRT19P087273EBI-398610,EBI-742756
KRT31Q153233EBI-398610,EBI-948001
KRT40Q6A1623EBI-398610,EBI-10171697
KRTAP10-5P603703EBI-398610,EBI-10172150
KRTAP10-8P604103EBI-398610,EBI-10171774
KRTAP10-9P604113EBI-398610,EBI-10172052
LZTS2Q9BRK43EBI-398610,EBI-741037
MAGED1Q9Y5V33EBI-398610,EBI-716006
MAPRE3Q9UPY83EBI-398610,EBI-726739
MIPOL1Q8TD103EBI-398610,EBI-2548751
MYOGP151733EBI-398610,EBI-3906629
NECAB2H3BTW23EBI-398610,EBI-10172876
NOTCH2NLQ7Z3S93EBI-398610,EBI-945833
PRDM14Q9GZV83EBI-398610,EBI-3957793
RELQ048643EBI-398610,EBI-307352
SPAG5Q96R063EBI-398610,EBI-413317
SPERTQ8NA613EBI-398610,EBI-741724
SPRY2O435973EBI-398610,EBI-742487
TADA2AO754783EBI-398610,EBI-742268
TCF4P158843EBI-398610,EBI-533224
TMCC2Q7Z6C63EBI-398610,EBI-10177480
TRIM27P143733EBI-398610,EBI-719493
TRIM54Q9BYV23EBI-398610,EBI-2130429
UBXN11Q5T1243EBI-398610,EBI-746004
USHBP1Q8N6Y03EBI-398610,EBI-739895
USP54Q70EL13EBI-398610,EBI-946185
ZBTB9Q96C003EBI-398610,EBI-395708

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114856. 77 interactors.
DIPiDIP-32578N.
IntActiO60573. 51 interactors.
MINTiMINT-1440115.
STRINGi9606.ENSP00000258416.

Structurei

Secondary structure

1245
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi55 – 67Combined sources13
Helixi75 – 81Combined sources7
Beta strandi82 – 90Combined sources9
Helixi91 – 98Combined sources8
Helixi104 – 106Combined sources3
Beta strandi109 – 117Combined sources9
Turni127 – 131Combined sources5
Beta strandi133 – 139Combined sources7
Helixi144 – 156Combined sources13
Beta strandi166 – 173Combined sources8
Beta strandi178 – 185Combined sources8
Helixi190 – 203Combined sources14
Beta strandi212 – 216Combined sources5
Helixi217 – 222Combined sources6

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiO60573.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni54 – 57EIF4EBP1/2/3 binding4
Regioni78 – 797-methylguanosine-containing mRNA cap bindingBy similarity2
Regioni95 – 99EIF4EBP1/2/3 binding5
Regioni124 – 1257-methylguanosine-containing mRNA cap binding2
Regioni150 – 157EIF4EBP1/2/3 binding8
Regioni174 – 1797-methylguanosine-containing mRNA cap binding6
Regioni222 – 2247-methylguanosine-containing mRNA cap bindingBy similarity3

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1669. Eukaryota.
COG5053. LUCA.
GeneTreeiENSGT00520000055549.
HOGENOMiHOG000186751.
HOVERGENiHBG107087.
InParanoidiO60573.
KOiK03259.
OMAiLLFHNLW.
OrthoDBiEOG091G0IEX.
PhylomeDBiO60573.
TreeFamiTF101529.

Family and domain databases

Gene3Di3.30.760.10. 1 hit.
InterProiIPR023398. TIF_eIF4e-like.
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:August 1, 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)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 27MNNKF…STQKD → MMTVGTMIRMKKTAHRKI in AAC39871 (PubMed:9653160).CuratedAdd BLAST27

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054783223 – 234MPGRL…QRLLF → DNSSFRNTKITL in isoform 2. CuratedAdd BLAST12
Alternative sequenceiVSP_054784235 – 245Missing in isoform 2. CuratedAdd BLAST11

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.
UCSCiuc002vtb.3. human. [O60573-1]

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JGBX-ray1.70A45-234[»]
2JGCX-ray2.40A45-234[»]
ProteinModelPortaliO60573.
SMRiO60573.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114856. 77 interactors.
DIPiDIP-32578N.
IntActiO60573. 51 interactors.
MINTiMINT-1440115.
STRINGi9606.ENSP00000258416.

PTM databases

iPTMnetiO60573.
PhosphoSitePlusiO60573.

Proteomic databases

EPDiO60573.
PaxDbiO60573.
PeptideAtlasiO60573.
PRIDEiO60573.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000258416; ENSP00000258416; ENSG00000135930. [O60573-1]
ENST00000409098; ENSP00000386996; ENSG00000135930. [O60573-2]
GeneIDi9470.
KEGGihsa:9470.
UCSCiuc002vtb.3. human. [O60573-1]

Organism-specific databases

CTDi9470.
DisGeNETi9470.
GeneCardsiEIF4E2.
HGNCiHGNC:3293. EIF4E2.
HPAiHPA019253.
MIMi605895. gene.
neXtProtiNX_O60573.
OpenTargetsiENSG00000135930.
PharmGKBiPA27720.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1669. Eukaryota.
COG5053. LUCA.
GeneTreeiENSGT00520000055549.
HOGENOMiHOG000186751.
HOVERGENiHBG107087.
InParanoidiO60573.
KOiK03259.
OMAiLLFHNLW.
OrthoDBiEOG091G0IEX.
PhylomeDBiO60573.
TreeFamiTF101529.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135930-MONOMER.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000135930.
CleanExiHS_EIF4E2.
ExpressionAtlasiO60573. baseline and differential.
GenevisibleiO60573. HS.

Family and domain databases

Gene3Di3.30.760.10. 1 hit.
InterProiIPR023398. TIF_eIF4e-like.
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...

Entry informationi

Entry nameiIF4E2_HUMAN
AccessioniPrimary (citable) accession number: O60573
Secondary accession number(s): B8ZZJ9, O75349
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 11, 2003
Last sequence update: August 1, 1998
Last modified: November 2, 2016
This is version 148 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

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 one 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.