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UniProtKB - P06730 (IF4E_HUMAN)

Entry version 227 (07 Apr 2021)
Sequence version 2 (01 Feb 1996)
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Protein

Eukaryotic translation initiation factor 4E

Gene

EIF4E

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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 (PubMed:16271312, PubMed:22578813). In addition to its role in translation initiation, also acts as a regulator of translation and stability in the cytoplasm (PubMed:24335285). Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression: in the complex, EIF4E mediates the binding to the mRNA cap (By similarity). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). In P-bodies, component of a complex that mediates the storage of translationally inactive mRNAs in the cytoplasm and prevents their degradation (PubMed:24335285). May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development (By similarity).By similarity3 Publications

Caution

Was originally thought to be phosphorylated on Ser-53 (PubMed:3112145); this was later shown to be wrong (PubMed:7665584).2 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionInitiation factor, RNA-binding
Biological processHost-virus interaction, Protein biosynthesis, Translation regulation

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P06730

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1169408, ISG15 antiviral mechanism
R-HSA-156827, L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-159227, Transport of the SLBP independent Mature mRNA
R-HSA-159230, Transport of the SLBP Dependant Mature mRNA
R-HSA-159231, Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-166208, mTORC1-mediated signalling
R-HSA-429947, Deadenylation of mRNA
R-HSA-72649, Translation initiation complex formation
R-HSA-72662, Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
R-HSA-72702, Ribosomal scanning and start codon recognition
R-HSA-72706, GTP hydrolysis and joining of the 60S ribosomal subunit

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P06730

SIGNOR Signaling Network Open Resource

More...SIGNORi		P06730

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Eukaryotic translation initiation factor 4E1 Publication
Short name:
eIF-4E
Short name:
eIF4E
Alternative name(s):
eIF-4F 25 kDa subunit
mRNA cap-binding protein1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:EIF4EImported
Synonyms:EIF4EL1, EIF4F
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 4

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:3287, EIF4E

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		133440, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P06730

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000151247.12

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Autism 19 (AUTS19)1 Publication
Disease susceptibility is associated with variants affecting the gene represented in this entry. A heterozygous single-nucleotide insertion has been found in families affected by autism. The variant results in increased promoter activity and is involved in disease pathogenesis through EIF4E deregulation (PubMed:19556253).1 Publication
Disease descriptionA complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation.
Related information in OMIM
A chromosomal aberration involving EIF4E has been found in a patient with classic autism. Translocation t(45)(q23q31.3). The breakpoint on chromosome 4 is located 56 kb downstream of EIF4E (PubMed:19556253).1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi53S → A or D: No effect on phosphorylation level nor incorporation into eIF4F complex. 2 Publications1
Mutagenesisi73W → A: Abolishes binding to EIF4EBP1. Impairs interaction with DDX3X. 2 Publications1
Mutagenesisi102W → L: Decrease in mRNA cap binding; when associated with A-105. 1 Publication1
Mutagenesisi103E → A: No effect. 1 Publication1
Mutagenesisi104D → A: No effect. 1 Publication1
Mutagenesisi105E → A: Decrease in mRNA cap binding; when associated with L-102. 1 Publication1
Mutagenesisi119K → A: Higher affinity for EIF4G1. 1 Publication1
Mutagenesisi209S → A: Abolished resistance to cellular stress and DNA-damaging agents. 1 Publication1
Mutagenesisi209S → D: Phosphomimetic mutant; confers resistance to cellular stress and DNA-damaging agents. 1 Publication1

Keywords - Diseasei

Autism, Autism spectrum disorder

Organism-specific databases

DisGeNET

More...DisGeNETi		1977

MalaCards human disease database

More...MalaCardsi		EIF4E
MIMi615091, phenotype

Open Targets

More...OpenTargetsi		ENSG00000151247

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		106, NON RARE IN EUROPE: Autism

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA27714

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P06730, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL4848

Drug and drug target database

More...DrugBanki		DB01960, 7-methyl-7,8-dihydroguanosine-5'-diphosphate
DB01649, 7-methyl-GpppA
DB02716, 7-methyl-guanosine-5'-triphosphate
DB05165, LY2275796
DB08217, S-[(1-Hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl] methanesulfonothioate

DrugCentral

More...DrugCentrali		P06730

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		EIF4E

Domain mapping of disease mutations (DMDM)

More...DMDMi		1352435

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedCombined sources1 Publication
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001936342 – 217Eukaryotic translation initiation factor 4EAdd BLAST216

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylalanineCombined sources1
Modified residuei22PhosphothreonineCombined sources1
Modified residuei209Phosphoserine; by PKC and MKNK24 Publications1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex.7 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P06730

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P06730

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P06730

MaxQB - The MaxQuant DataBase

More...MaxQBi		P06730

PeptideAtlas

More...PeptideAtlasi		P06730

PRoteomics IDEntifications database

More...PRIDEi		P06730

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		51914 [P06730-1]
51915 [P06730-2]
51916 [P06730-3]

Consortium for Top Down Proteomics

More...TopDownProteomicsi		P06730-1 [P06730-1]

2D gel databases

USC-OGP 2-DE database

More...OGPi		P06730

REPRODUCTION-2DPAGE

More...REPRODUCTION-2DPAGEi		IPI00027485

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P06730

MetOSite database of methionine sulfoxide sites

More...MetOSitei		P06730

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P06730

SwissPalm database of S-palmitoylation events

More...SwissPalmi		P06730

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000151247, Expressed in calcaneal tendon and 236 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P06730, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P06730, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000151247, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions (PubMed:11408474, PubMed:11879179, PubMed:16271312, PubMed:17631896). It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3 (PubMed:8521827, PubMed:11408474, PubMed:11879179, PubMed:12975586). EIF4E is also known to interact with other partners (PubMed:8521827, PubMed:11408474, PubMed:11879179, PubMed:12975586).

Interacts with EIF4ENIF1/4E-T; promotes recruitment to P-bodies and import into the nucleus (PubMed:10856257, PubMed:16157702, PubMed:23991149, PubMed:24335285, PubMed:28487484). Hypophosphorylated 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 (PubMed:8521827, PubMed:16271312, PubMed:21661078, PubMed:24207126, PubMed:25533957, PubMed:25702871).

Interacts mutually exclusive with EIF4A1 or EIF4A2 (PubMed:11408474).

Interacts with NGDN and PIWIL2 (By similarity).

Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1 (By similarity).

Interacts directly with CYFIP1 (By similarity).

Interacts with CLOCK (By similarity). Binds to MKNK2 in nucleus (PubMed:12897141).

Interacts with LIMD1, WTIP and AJUBA (PubMed:20616046).

Interacts with APOBEC3G in an RNA-dependent manner (PubMed:16699599).

Interacts with LARP1 (PubMed:20430826).

Interacts with METTL3 (PubMed:27117702).

Interacts with RBM24; this interaction prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly of translation initiation complex (PubMed:29358667).

Interacts with DDX3X; interaction is direct and in an RNA-independent manner; this interaction enhances EIF4E cap-binding ability and is required for the repression of cap-dependent translation and the increase of IRES-mediated translation (PubMed:17667941, PubMed:21883093, PubMed:28733330). DDX3X competes with EIF4G1 for interaction with EIF4E (PubMed:17667941, PubMed:21883093).

By similarity24 Publications

(Microbial infection) Interacts with Lassa virus Z protein.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		108292, 81 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...ComplexPortali		CPX-2666, Eukaryotic translation initiation factor 4F, EIF4A1 and EIF4G1 variant
CPX-5634, Eukaryotic translation initiation factor 4F, EIF4A2 and EIF4G1 variant
CPX-5635, Eukaryotic translation initiation factor 4F, EIF4A1 and EIF4G3 variant
CPX-5636, Eukaryotic translation initiation factor 4F, EIF4A2 and EIF4G3 variant

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		P06730

Database of interacting proteins

More...DIPi		DIP-22N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		P06730

Protein interaction database and analysis system

More...IntActi		P06730, 64 interactors

Molecular INTeraction database

More...MINTi		P06730

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P06730

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P06730, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1217
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Biological Magnetic Resonance Data Bank

More...BMRBi		P06730

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P06730

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P06730

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni37 – 40EIF4EBP1/2/3 binding1 Publication4
Regioni56 – 577-methylguanosine-containing mRNA cap binding3 Publications2
Regioni73 – 77EIF4EBP1/2/3 binding1 Publication5
Regioni102 – 1037-methylguanosine-containing mRNA cap binding3 Publications2
Regioni132 – 139EIF4EBP1/2/3 binding1 Publication8
Regioni157 – 1627-methylguanosine-containing mRNA cap binding3 Publications6
Regioni205 – 2077-methylguanosine-containing mRNA cap binding3 Publications3

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the eukaryotic initiation factor 4E family.Curated

Phylogenomic databases

Ensembl GeneTree

More...GeneTreei		ENSGT00940000154194

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_043552_1_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P06730

Identification of Orthologs from Complete Genome Data

More...OMAi		NDIRPEW

Database of Orthologous Groups

More...OrthoDBi		1394271at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P06730

TreeFam database of animal gene trees

More...TreeFami		TF101526

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.30.760.10, 1 hit

Intrinsically Disordered proteins with Extensive Annotations and Literature

More...IDEALi		IID00341

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR023398, TIF_eIF4e-like
IPR001040, TIF_eIF_4E
IPR019770, TIF_eIF_4E_CS

The PANTHER Classification System

More...PANTHERi		PTHR11960, PTHR11960, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF01652, IF4E, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF55418, SSF55418, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00813, IF4E, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P06730-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
MATVEPETTP TPNPPTTEEE KTESNQEVAN PEHYIKHPLQ NRWALWFFKN 
        60         70         80         90        100
DKSKTWQANL RLISKFDTVE DFWALYNHIQ LSSNLMPGCD YSLFKDGIEP 
       110        120        130        140        150
MWEDEKNKRG GRWLITLNKQ QRRSDLDRFW LETLLCLIGE SFDDYSDDVC 
       160        170        180        190        200
GAVVNVRAKG DKIAIWTTEC ENREAVTHIG RVYKERLGLP PKIVIGYQSH 
       210 
ADTATKSGST TKNRFVV
Length:217
Mass (Da):25,097
Last modified:February 1, 1996 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iB869B8DE615E699D
GO
Isoform 2 (identifier: P06730-2) [UniParc]FASTAAdd to basket

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

Show »
Length:248
Mass (Da):28,778
Checksum:i3869E3249A241190
GO
Isoform 3 (identifier: P06730-3) [UniParc]FASTAAdd to basket

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

Show »
Length:237
Mass (Da):27,260
Checksum:iD4925235C678DE08
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RBW1D6RBW1_HUMAN
Eukaryotic translation initiation f...
EIF4E
245Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0Y8J7H0Y8J7_HUMAN
Eukaryotic translation initiation f...
EIF4E
155Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
D6RFJ3D6RFJ3_HUMAN
Eukaryotic translation initiation f...
EIF4E
42Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti127D → N in AAH12611 (PubMed:15489334).Curated1

<p>This subsection of the 'Sequence' section reports information derived from mass spectrometry experiments done on the entire protein or on biologically active derived peptide(s).<p><a href='/help/mass_spectrometry' target='_top'>More...</a></p>Mass spectrometryi

Molecular mass is 24964.3 Da. Determined by ESI. 1 Publication
Molecular mass is 24960 Da. Determined by ESI. 1 Publication

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0435911 – 6MATVEP → MLDLTSRGQVGTSRRMAEAA CSAHFL in isoform 3. 1 Publication6
Alternative sequenceiVSP_042014133T → TRWDLAMLPRLVSNFWPQVI LPLQPPKVLELQ in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
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.

The Consensus CDS (CCDS) project

More...CCDSi		CCDS34031.1 [P06730-1]
CCDS47109.1 [P06730-3]
CCDS54779.1 [P06730-2]

Protein sequence database of the Protein Information Resource

More...PIRi		A26411

NCBI Reference Sequences

More...RefSeqi		NP_001124150.1, NM_001130678.2 [P06730-3]
NP_001124151.1, NM_001130679.2 [P06730-2]
NP_001317946.1, NM_001331017.1
NP_001959.1, NM_001968.4 [P06730-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000280892; ENSP00000280892; ENSG00000151247 [P06730-3]
ENST00000450253; ENSP00000389624; ENSG00000151247 [P06730-1]
ENST00000505992; ENSP00000425561; ENSG00000151247 [P06730-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		1977

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:1977

UCSC genome browser

More...UCSCi		uc003hue.3, human [P06730-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34031.1 [P06730-1]
CCDS47109.1 [P06730-3]
CCDS54779.1 [P06730-2]
PIRiA26411
RefSeqiNP_001124150.1, NM_001130678.2 [P06730-3]
NP_001124151.1, NM_001130679.2 [P06730-2]
NP_001317946.1, NM_001331017.1
NP_001959.1, NM_001968.4 [P06730-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IPBX-ray2.00A1-217[»]
1IPCX-ray2.00A1-217[»]
1WKWX-ray2.10A27-217[»]
2GPQNMR-A1-217[»]
2V8WX-ray2.30A/E1-217[»]
2V8XX-ray2.30A/E1-217[»]
2V8YX-ray2.10A/E1-217[»]
2W97X-ray2.29A/B1-217[»]
3AM7X-ray2.20A27-217[»]
3TF2X-ray2.10A/B/C/D1-217[»]
3U7XX-ray2.10A/B1-217[»]
4AZAX-ray2.16A/C1-217[»]
4BEAX-ray2.57A1-217[»]
4DT6X-ray2.60A1-217[»]
4DUMX-ray2.95A1-217[»]
4TPWX-ray1.50A/B28-217[»]
4TQBX-ray1.59A/B28-217[»]
4TQCX-ray1.80A/B28-217[»]
4UEDX-ray1.75A36-217[»]
5EHCX-ray2.40A1-217[»]
5EI3X-ray1.71A1-217[»]
5EIRX-ray2.69A1-217[»]
5EKVX-ray3.61A/C1-217[»]
5GW6X-ray1.97A23-217[»]
5T46X-ray1.53A/C1-217[»]
5ZJYX-ray1.59A28-217[»]
5ZJZX-ray1.67A28-217[»]
5ZK5X-ray2.25A28-217[»]
5ZK7X-ray2.12A/B28-217[»]
5ZK9X-ray1.76A28-217[»]
5ZMLX-ray1.80A27-217[»]
BMRBiP06730
SMRiP06730
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi108292, 81 interactors
ComplexPortaliCPX-2666, Eukaryotic translation initiation factor 4F, EIF4A1 and EIF4G1 variant
CPX-5634, Eukaryotic translation initiation factor 4F, EIF4A2 and EIF4G1 variant
CPX-5635, Eukaryotic translation initiation factor 4F, EIF4A1 and EIF4G3 variant
CPX-5636, Eukaryotic translation initiation factor 4F, EIF4A2 and EIF4G3 variant
CORUMiP06730
DIPiDIP-22N
ELMiP06730
IntActiP06730, 64 interactors
MINTiP06730

Chemistry databases

BindingDBiP06730
ChEMBLiCHEMBL4848
DrugBankiDB01960, 7-methyl-7,8-dihydroguanosine-5'-diphosphate
DB01649, 7-methyl-GpppA
DB02716, 7-methyl-guanosine-5'-triphosphate
DB05165, LY2275796
DB08217, S-[(1-Hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl] methanesulfonothioate
DrugCentraliP06730

PTM databases

iPTMnetiP06730
MetOSiteiP06730
PhosphoSitePlusiP06730
SwissPalmiP06730

Genetic variation databases

BioMutaiEIF4E
DMDMi1352435

2D gel databases

OGPiP06730
REPRODUCTION-2DPAGEiIPI00027485

Proteomic databases

EPDiP06730
jPOSTiP06730
MassIVEiP06730
MaxQBiP06730
PeptideAtlasiP06730
PRIDEiP06730
ProteomicsDBi51914 [P06730-1]
51915 [P06730-2]
51916 [P06730-3]
TopDownProteomicsiP06730-1 [P06730-1]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		3421, 953 antibodies

The DNASU plasmid repository

More...DNASUi		1977

Genome annotation databases

EnsembliENST00000280892; ENSP00000280892; ENSG00000151247 [P06730-3]
ENST00000450253; ENSP00000389624; ENSG00000151247 [P06730-1]
ENST00000505992; ENSP00000425561; ENSG00000151247 [P06730-2]
GeneIDi1977
KEGGihsa:1977
UCSCiuc003hue.3, human [P06730-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		1977
DisGeNETi1977

GeneCards: human genes, protein and diseases

More...GeneCardsi		EIF4E
HGNCiHGNC:3287, EIF4E
HPAiENSG00000151247, Low tissue specificity
MalaCardsiEIF4E
MIMi133440, gene
615091, phenotype
neXtProtiNX_P06730
OpenTargetsiENSG00000151247
Orphaneti106, NON RARE IN EUROPE: Autism
PharmGKBiPA27714
VEuPathDBiHostDB:ENSG00000151247.12

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

GeneTreeiENSGT00940000154194
HOGENOMiCLU_043552_1_1_1
InParanoidiP06730
OMAiNDIRPEW
OrthoDBi1394271at2759
PhylomeDBiP06730
TreeFamiTF101526

Enzyme and pathway databases

PathwayCommonsiP06730
ReactomeiR-HSA-1169408, ISG15 antiviral mechanism
R-HSA-156827, L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-159227, Transport of the SLBP independent Mature mRNA
R-HSA-159230, Transport of the SLBP Dependant Mature mRNA
R-HSA-159231, Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-166208, mTORC1-mediated signalling
R-HSA-429947, Deadenylation of mRNA
R-HSA-72649, Translation initiation complex formation
R-HSA-72662, Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
R-HSA-72702, Ribosomal scanning and start codon recognition
R-HSA-72706, GTP hydrolysis and joining of the 60S ribosomal subunit
SignaLinkiP06730
SIGNORiP06730

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		1977, 728 hits in 973 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		EIF4E, human
EvolutionaryTraceiP06730

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		EIF4E

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		1977
PharosiP06730, Tchem

Protein Ontology

More...PROi		PR:P06730
RNActiP06730, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000151247, Expressed in calcaneal tendon and 236 other tissues
ExpressionAtlasiP06730, baseline and differential
GenevisibleiP06730, HS

Family and domain databases

Gene3Di3.30.760.10, 1 hit
IDEALiIID00341
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

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiIF4E_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P06730
Secondary accession number(s): B7Z6V1, D6RCQ6, Q96E95
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: February 1, 1996
Last modified: April 7, 2021
This is version 227 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Reference proteome

Documents

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