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    EIF4E2 eukaryotic translation initiation factor 4E family member 2 [ Homo sapiens (human) ]

    Gene ID: 9470, updated on 10-Dec-2024

    Summary

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    Official Symbol
    EIF4E2provided by HGNC
    Official Full Name
    eukaryotic translation initiation factor 4E family member 2provided by HGNC
    Primary source
    HGNC:HGNC:3293
    See related
    Ensembl:ENSG00000135930 MIM:605895; AllianceGenome:HGNC:3293
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    4EHP; IF4e; 4E-LP; h4EHP; EIF4EL3
    Summary
    Enables RNA 7-methylguanosine cap binding activity; mRNA cap binding activity; and ubiquitin protein ligase binding activity. Involved in negative regulation of translational initiation; negative regulation of type I interferon-mediated signaling pathway; and rescue of stalled ribosome. Acts upstream of with a positive effect on miRNA-mediated gene silencing by inhibition of translation. Acts upstream of or within negative regulation of translation. Located in P-body. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Ubiquitous expression in kidney (RPKM 16.4), colon (RPKM 13.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See EIF4E2 in Genome Data Viewer
    Location:
    2q37.1
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (232550689..232583644)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (233037473..233070437)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (233415399..233448354)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17323 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12460 Neighboring gene cholinergic receptor nicotinic gamma subunit Neighboring gene tigger transposable element derived 1 Neighboring gene microRNA 5001 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:233432608-233433807 Neighboring gene uncharacterized LOC105373929 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:233465129-233465628 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17324 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17325 Neighboring gene EF-hand domain family member D1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12461 Neighboring gene Sharpr-MPRA regulatory region 9991 Neighboring gene RNA, 7SL, cytoplasmic 359, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:233526805-233527304 Neighboring gene small nucleolar RNA U13

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap-binding protein. Rom E, et al. J Biol Chem, 1998 May 22. PMID 9582349
    2. MicroRNAs recruit eIF4E2 to repress translation of target mRNAs. Chen S, et al. Protein Cell, 2017 Oct. PMID 28755203, Free PMC Article
    3. High EIF4E2 expression is an independent prognostic risk factor for poor overall survival and recurrence-free survival in uveal melanoma. Yang B, et al. Exp Eye Res, 2021 May. PMID 33785306
    4. Cancer cells exploit eIF4E2-directed synthesis of hypoxia response proteins to drive tumor progression. Uniacke J, et al. Cancer Res, 2014 Mar 1. PMID 24408918
    5. Weak binding affinity of human 4EHP for mRNA cap analogs. Zuberek J, et al. RNA, 2007 May. PMID 17369309, Free PMC Article

    See all (116) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. METTL16 promotes translation and lung tumorigenesis by sequestering cytoplasmic eIF4E2.
      Title: METTL16 promotes translation and lung tumorigenesis by sequestering cytoplasmic eIF4E2.
    2. Translational repression of NMD targets by GIGYF2 and EIF4E2.
      Title: Translational repression of NMD targets by GIGYF2 and EIF4E2.
    3. 4EHP and GIGYF1/2 Mediate Translation-Coupled Messenger RNA Decay.
      Title: 4EHP and GIGYF1/2 Mediate Translation-Coupled Messenger RNA Decay.
    4. High EIF4E2 expression is an independent prognostic risk factor for poor overall survival and recurrence-free survival in uveal melanoma.
      Title: High EIF4E2 expression is an independent prognostic risk factor for poor overall survival and recurrence-free survival in uveal melanoma.
    5. microRNA-induced translational control of antiviral immunity by the cap-binding protein 4EHP.
      Title: microRNA-induced translational control of antiviral immunity by the cap-binding protein 4EHP.
    6. GIGYF2 and 4EHP Inhibit Translation Initiation of Defective Messenger RNAs to Assist Ribosome-Associated Quality Control.
      Title: GIGYF2 and 4EHP Inhibit Translation Initiation of Defective Messenger RNAs to Assist Ribosome-Associated Quality Control.
    7. The authors that the Dusp6 mRNA, which encodes an ERK1/2 phosphatase, is translationally repressed by 4EHP and a specific miRNA, miR-145.
      Title: Translational control of ERK signaling through miRNA/4EHP-directed silencing.
    8. cadherin-22 is upregulated in hypoxia via mTORC1-independent translational control by the initiation factor eIF4E2 functioning as a hypoxia-specific cell-surface molecule involved in cancer cell migration, invasion and adhesion.
      Title: Hypoxia activates cadherin-22 synthesis via eIF4E2 to drive cancer cell migration, invasion and adhesion.
    9. cap-binding activity contributes to the translational silencing by miRNAs through the CCR4-NOT complex
      Title: Cap-binding protein 4EHP effects translation silencing by microRNAs.
    10. We performed bioinformatics analyses of ESTs and the 3'UTRs of the main transcript splice variants of the translational initiation factor eIF4E1 and its family members, eIF4E2 and eIF4E3. We propose to elucidate the minor splice variants of eIF4E2 and eIF4E3 in great detail because they might produce proteins with modified features that fulfill different cellular roles from their major counterparts.
      Title: Major splice variants and multiple polyadenylation site utilization in mRNAs encoding human translation initiation factors eIF4E1 and eIF4E3 regulate the translational regulators?
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association study on overall survival of advanced non-small cell lung cancer patients treated with carboplatin and paclitaxel.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ23586

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA 7-methylguanosine cap binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA 7-methylguanosine cap binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables RNA binding HDA PubMed 
    enables RNA cap binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables mRNA cap binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables translation factor activity, RNA binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables translation initiation factor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    acts_upstream_of_positive_effect miRNA-mediated gene silencing by inhibition of translation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of translation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of translational initiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of type I interferon-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in rescue of stalled ribosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in translational initiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in P-body IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    part_of eukaryotic translation initiation factor 4F complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    eukaryotic translation initiation factor 4E type 2
    Names
    eIF-4E type 2
    eIF4E-like cap-binding protein
    eIF4E-like protein 4E-LP
    eukaryotic translation initiation factor 4E homologous protein
    eukaryotic translation initiation factor 4E-like 3
    mRNA cap-binding protein type 3

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001276336.2 → NP_001263265.1  eukaryotic translation initiation factor 4E type 2 isoform C

      See identical proteins and their annotated locations for NP_001263265.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) uses an alternate 3' terminal exon and it thus differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (C) has a distinct C-terminus and is shorter than isoform A.
      Source sequence(s)
      AB209519, AK027239, DA201209, DA592245
      Consensus CDS
      CCDS63159.1
      UniProtKB/TrEMBL
      Q59FE1
      Related
      ENSP00000386996.1, ENST00000409098.5
      Conserved Domains (1) summary
      pfam01652
      Location:55 → 214
      IF4E; Eukaryotic initiation factor 4E

    2. NM_001276337.2 → NP_001263266.1  eukaryotic translation initiation factor 4E type 2 isoform D

      See identical proteins and their annotated locations for NP_001263266.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) lacks an alternate in-frame exon in the 5' coding region, and uses an alternate 3' terminal exon and thus differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (D) has a distinct C-terminus and is shorter than isoform A.
      Source sequence(s)
      AB209519, AK027239, CD684451, DA201209, DA592245, DA992544
      Consensus CDS
      CCDS74671.1
      UniProtKB/TrEMBL
      B4E1E4, B9A023
      Related
      ENSP00000386983.1, ENST00000409394.5
      Conserved Domains (1) summary
      pfam01652
      Location:46 → 169
      IF4E; Eukaryotic initiation factor 4E

    3. NM_001282958.2 → NP_001269887.1  eukaryotic translation initiation factor 4E type 2 isoform B

      See identical proteins and their annotated locations for NP_001269887.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) contains alternate 3' exon structure and it thus differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (B) has a distinct C-terminus and is shorter than isoform A.
      Source sequence(s)
      AB209519, AK027239, BG913475, DA201209, DA408433, DA592245
      Consensus CDS
      CCDS63158.1
      UniProtKB/TrEMBL
      B8ZZ50, B9A044
      Related
      ENSP00000387336.1, ENST00000409514.5
      Conserved Domains (1) summary
      pfam01652
      Location:55 → 214
      IF4E; Eukaryotic initiation factor 4E

    4. NM_001330201.2 → NP_001317130.1  eukaryotic translation initiation factor 4E type 2 isoform E

      Status: VALIDATED

      Source sequence(s)
      AC092165, AC093383
      Consensus CDS
      CCDS82579.1
      UniProtKB/TrEMBL
      B4E1E4, B8ZZL3
      Related
      ENSP00000386424.1, ENST00000409322.5
      Conserved Domains (1) summary
      pfam01652
      Location:46 → 169
      IF4E; Eukaryotic initiation factor 4E

    5. NM_001330202.2 → NP_001317131.1  eukaryotic translation initiation factor 4E type 2 isoform G

      Status: VALIDATED

      Source sequence(s)
      AC092165, AC093383
      UniProtKB/TrEMBL
      C9JEL3
      Related
      ENSP00000390904.1, ENST00000454501.1
      Conserved Domains (1) summary
      pfam01652
      Location:50 → 209
      IF4E; Eukaryotic initiation factor 4E

    6. NM_001330203.2 → NP_001317132.1  eukaryotic translation initiation factor 4E type 2 isoform F

      Status: VALIDATED

      Source sequence(s)
      AC073254, AC092165
      Consensus CDS
      CCDS92971.1
      UniProtKB/TrEMBL
      A0A8I5KSA5, B4E1E4
      Related
      ENSP00000508671.1, ENST00000687222.1
      Conserved Domains (1) summary
      pfam01652
      Location:46 → 169
      IF4E; Eukaryotic initiation factor 4E

    7. NM_004846.4 → NP_004837.1  eukaryotic translation initiation factor 4E type 2 isoform A

      See identical proteins and their annotated locations for NP_004837.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (A).
      Source sequence(s)
      BC005874
      Consensus CDS
      CCDS2496.1
      UniProtKB/Swiss-Prot
      B8ZZJ9, O60573, O75349
      UniProtKB/TrEMBL
      B9A044, Q53RG0
      Related
      ENSP00000258416.3, ENST00000258416.8
      Conserved Domains (1) summary
      pfam01652
      Location:55 → 214
      IF4E; Eukaryotic initiation factor 4E

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      232550689..232583644
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      233037473..233070437
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O60573.1 GenPept UniProtKB/Swiss-Prot:O60573

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools