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O60573

- IF4E2_HUMAN

UniProt

O60573 - IF4E2_HUMAN

Protein

Eukaryotic translation initiation factor 4E type 2

Gene

EIF4E2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 129 (01 Oct 2014)
      Sequence version 1 (01 Aug 1998)
      Previous versions | rss
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    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. protein binding Source: UniProtKB
    3. RNA cap binding Source: ProtInc
    4. translation factor activity, nucleic acid binding Source: ProtInc
    5. translation initiation factor activity Source: UniProtKB-KW
    6. 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

    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: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:3293. EIF4E2.

    Subcellular locationi

    GO - Cellular componenti

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

    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

    ArrayExpressiO60573.
    BgeeiO60573.
    CleanExiHS_EIF4E2.
    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. 21 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 – 6713
    Helixi75 – 817
    Beta strandi82 – 909
    Helixi91 – 988
    Helixi104 – 1063
    Beta strandi109 – 1179
    Turni127 – 1315
    Beta strandi133 – 1397
    Helixi144 – 15613
    Beta strandi166 – 1738
    Beta strandi178 – 1858
    Helixi190 – 20314
    Beta strandi212 – 2165
    Helixi217 – 2226

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    HOGENOMiHOG000186751.
    HOVERGENiHBG107087.
    InParanoidiO60573.
    KOiK03259.
    OMAiDSIKAWE.
    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. Align

    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

    MNNKFDALKD DDSGDHDQNE ENSTQKDGEK EKTERDKNQS SSKRKAVVPG    50
    PAEHPLQYNY TFWYSRRTPG RPTSSQSYEQ NIKQIGTFAS VEQFWRFYSH 100
    MVRPGDLTGH SDFHLFKEGI KPMWEDDANK NGGKWIIRLR KGLASRCWEN 150
    LILAMLGEQF MVGEEICGAV VSVRFQEDII SIWNKTASDQ ATTARIRDTL 200
    RRVLNLPPNT IMEYKTHTDS IKMPGRLGPQ RLLFQNLWKP RLNVP 245
    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)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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS2496.1. [O60573-1 ]
    CCDS63159.1. [O60573-2 ]
    RefSeqi NP_001263265.1. NM_001276336.1. [O60573-2 ]
    NP_004837.1. NM_004846.3. [O60573-1 ]
    UniGenei Hs.292026.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2JGB X-ray 1.70 A 45-234 [» ]
    2JGC X-ray 2.40 A 45-234 [» ]
    ProteinModelPortali O60573.
    SMRi O60573. Positions 45-234.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114856. 21 interactions.
    DIPi DIP-32578N.
    IntActi O60573. 15 interactions.
    MINTi MINT-1440115.
    STRINGi 9606.ENSP00000258416.

    PTM databases

    PhosphoSitei O60573.

    Proteomic databases

    MaxQBi O60573.
    PaxDbi O60573.
    PRIDEi O60573.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000258416 ; ENSP00000258416 ; ENSG00000135930 . [O60573-1 ]
    ENST00000409098 ; ENSP00000386996 ; ENSG00000135930 . [O60573-2 ]
    GeneIDi 9470.
    KEGGi hsa:9470.
    UCSCi uc002vta.3. human. [O60573-1 ]
    uc002vtb.1. human.

    Organism-specific databases

    CTDi 9470.
    GeneCardsi GC02P233414.
    HGNCi HGNC:3293. EIF4E2.
    HPAi HPA019253.
    MIMi 605895. gene.
    neXtProti NX_O60573.
    PharmGKBi PA27720.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5053.
    HOGENOMi HOG000186751.
    HOVERGENi HBG107087.
    InParanoidi O60573.
    KOi K03259.
    OMAi DSIKAWE.
    OrthoDBi EOG7GQXWN.
    PhylomeDBi O60573.
    TreeFami TF101529.

    Enzyme and pathway databases

    Reactomei REACT_115831. ISG15 antiviral mechanism.

    Miscellaneous databases

    ChiTaRSi EIF4E2. human.
    EvolutionaryTracei O60573.
    GeneWikii EIF4E2.
    GenomeRNAii 9470.
    NextBioi 35481795.
    PROi O60573.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O60573.
    Bgeei O60573.
    CleanExi HS_EIF4E2.
    Genevestigatori O60573.

    Family and domain databases

    Gene3Di 3.30.760.10. 1 hit.
    InterProi IPR023398. TIF_eIF4e-like_dom.
    IPR001040. TIF_eIF_4E.
    IPR019770. TIF_eIF_4E_CS.
    [Graphical view ]
    PANTHERi PTHR11960. PTHR11960. 1 hit.
    Pfami PF01652. IF4E. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55418. SSF55418. 1 hit.
    PROSITEi PS00813. IF4E. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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(1998) [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(2004) [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(1998) [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(2005) [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(2004) [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(2003) [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(2007) [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(2009) [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(2007) [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 11, 2003
    Last sequence update: August 1, 1998
    Last modified: October 1, 2014
    This is version 129 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