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Protein

Eukaryotic translation initiation factor 4E type 2

Gene

EIF4E2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation (PubMed:9582349, PubMed:17368478, PubMed:25624349). Acts as a repressor of translation initiation (PubMed:22751931). In contrast to EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by competing with EIF4E and block assembly of eIF4F at the cap (By similarity).By similarity4 Publications

Sites

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

GO - Molecular functioni

  • 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

Keywordsi

Molecular functionInitiation factor, RNA-binding
Biological processProtein biosynthesis, Translation regulation

Enzyme and pathway databases

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
Short name:
h4EHP1 Publication
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

EuPathDBiHostDB:ENSG00000135930.13
HGNCiHGNC:3293 EIF4E2
MIMi605895 gene
neXtProtiNX_O60573

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi49475

PTM databases

iPTMnetiO60573
PhosphoSitePlusiO60573

Expressioni

Gene expression databases

BgeeiENSG00000135930
CleanExiHS_EIF4E2
ExpressionAtlasiO60573 baseline and differential
GenevisibleiO60573 HS

Organism-specific databases

HPAiHPA019253

Interactioni

Subunit structurei

Interacts with EIF4EBP1, EIF4EBP2 and EIF4EBP3 (PubMed:15153109, PubMed:17368478). Does not interact with eIF4G (EIF4G1, EIF4G2 or EIF4G3) (By similarity). Component of the 4EHP-GYF2 complex, at least composed of EIF4E2, GIGYF2 and ZNF598 (PubMed:22751931). Interacts with GIGYF2 (via the 4EHP-binding motif); the interaction is direct (PubMed:22751931).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114856, 145 interactors
DIPiDIP-32578N
IntActiO60573, 123 interactors
MINTiO60573
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

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
OMAiSHMIRPG
OrthoDBiEOG091G0IEX
PhylomeDBiO60573
TreeFamiTF101529

Family and domain databases

Gene3Di3.30.760.10, 1 hit
InterProiView protein in InterPro
IPR023398 TIF_eIF4e-like
IPR001040 TIF_eIF_4E
IPR019770 TIF_eIF_4E_CS
PANTHERiPTHR11960 PTHR11960, 1 hit
PfamiView protein in Pfam
PF01652 IF4E, 1 hit
SUPFAMiSSF55418 SSF55418, 1 hit
PROSITEiView protein in PROSITE
PS00813 IF4E, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiIF4E2_HUMAN
AccessioniPrimary (citable) accession number: O60573
Secondary accession number(s): B8ZZJ9, O75349
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 11, 2003
Last sequence update: August 1, 1998
Last modified: July 18, 2018
This is version 161 of the entry and version 1 of the sequence. See 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

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