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Database: UniProt
Entry: P63073
LinkDB: P63073
Original site: P63073 
ID   IF4E_MOUSE              Reviewed;         217 AA.
AC   P63073; P20415;
DT   13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT   13-SEP-2004, sequence version 1.
DT   11-DEC-2019, entry version 148.
DE   RecName: Full=Eukaryotic translation initiation factor 4E;
DE            Short=eIF-4E;
DE            Short=eIF4E;
DE            Short=mRNA cap-binding protein;
DE   AltName: Full=eIF-4F 25 kDa subunit;
GN   Name=Eif4e;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2663851;
RA   Altmann M., Mueller P.P., Pelletier J., Sonenberg N., Trachsel H.;
RT   "A mammalian translation initiation factor can substitute for its yeast
RT   homologue in vivo.";
RL   J. Biol. Chem. 264:12145-12147(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2037592;
RA   Jaramillo M., Pelletier J., Edery I., Nielsen P.J., Sonenberg N.;
RT   "Multiple mRNAs encode the murine translation initiation factor eIF-4E.";
RL   J. Biol. Chem. 266:10446-10451(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Colon, and Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   INTERACTION WITH NGDN.
RX   PubMed=16705177; DOI=10.1128/mcb.02470-05;
RA   Jung M.-Y., Lorenz L., Richter J.D.;
RT   "Translational control by neuroguidin, a eukaryotic initiation factor 4E
RT   and CPEB binding protein.";
RL   Mol. Cell. Biol. 26:4277-4287(2006).
RN   [5]
RP   PHOSPHORYLATION AT SER-209 BY MKNK2.
RX   PubMed=17689282; DOI=10.1016/j.biocel.2007.05.001;
RA   Shenberger J.S., Zhang L., Hughlock M.K., Ueda T., Watanabe-Fukunaga R.,
RA   Fukunaga R.;
RT   "Roles of mitogen-activated protein kinase signal-integrating kinases 1 and
RT   2 in oxidant-mediated eIF4E phosphorylation.";
RL   Int. J. Biochem. Cell Biol. 39:1828-1842(2007).
RN   [6]
RP   FUNCTION, INTERACTION WITH CYFIP1 AND FMR1, AND MUTAGENESIS OF TRP-73.
RX   PubMed=18805096; DOI=10.1016/j.cell.2008.07.031;
RA   Napoli I., Mercaldo V., Boyl P.P., Eleuteri B., Zalfa F., De Rubeis S.,
RA   Di Marino D., Mohr E., Massimi M., Falconi M., Witke W., Costa-Mattioli M.,
RA   Sonenberg N., Achsel T., Bagni C.;
RT   "The fragile X syndrome protein represses activity-dependent translation
RT   through CYFIP1, a new 4E-BP.";
RL   Cell 134:1042-1054(2008).
RN   [7]
RP   INTERACTION WITH PIWIL2.
RX   PubMed=19114715; DOI=10.1074/jbc.m809104200;
RA   Unhavaithaya Y., Hao Y., Beyret E., Yin H., Kuramochi-Miyagawa S.,
RA   Nakano T., Lin H.;
RT   "MILI, a PIWI-interacting RNA-binding protein, is required for germ Line
RT   stem cell self-renewal and appears to positively regulate translation.";
RL   J. Biol. Chem. 284:6507-6519(2009).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [9]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH CLOCK.
RX   PubMed=22900038; DOI=10.1371/journal.pone.0042695;
RA   Peruquetti R.L., de Mateo S., Sassone-Corsi P.;
RT   "Circadian proteins CLOCK and BMAL1 in the chromatoid body, a RNA
RT   processing granule of male germ cells.";
RL   PLoS ONE 7:E42695-E42695(2012).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 28-217 IN COMPLEX WITH MRNA CAP
RP   ANALOG.
RX   PubMed=9200613; DOI=10.1016/s0092-8674(00)80280-9;
RA   Marcotrigiano J., Gingras A.-C., Sonenberg N., Burley S.K.;
RT   "Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E)
RT   bound to 7-methyl-GDP.";
RL   Cell 89:951-961(1997).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 28-217 IN COMPLEX WITH MRNA CAP
RP   ANALOG AND EIF4EBP1.
RX   PubMed=10394359; DOI=10.1016/s1097-2765(01)80003-4;
RA   Marcotrigiano J., Gingras A.-C., Sonenberg N., Burley S.K.;
RT   "Cap-dependent translation initiation in eukaryotes is regulated by a
RT   molecular mimic of eIF4G.";
RL   Mol. Cell 3:707-716(1999).
CC   -!- FUNCTION: Recognizes and binds the 7-methylguanosine-containing mRNA
CC       cap during an early step in the initiation of protein synthesis and
CC       facilitates ribosome binding by inducing the unwinding of the mRNAs
CC       secondary structures. May play an important role in spermatogenesis
CC       through translational regulation of stage-specific mRNAs during germ
CC       cell development (By similarity). Its translation stimulation activity
CC       is repressed by binding to the complex CYFIP1-FMR1. Component of the
CC       CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates
CC       translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit
CC       mediates the binding to the mRNA cap. {ECO:0000250,
CC       ECO:0000269|PubMed:18805096}.
CC   -!- SUBUNIT: eIF4F is a multi-subunit complex, the composition of which
CC       varies with external and internal environmental conditions. It is
CC       composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. EIF4E is also
CC       known to interact with other partners. The interaction with EIF4ENIF1
CC       mediates the import into the nucleus. Hypophosphorylated EIF4EBP1,
CC       EIF4EBP2 and EIF4EBP3 compete with EIF4G1/EIF4G3 to interact with
CC       EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation
CC       of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3
CC       to bind and consequent initiation of translation. Rapamycin can
CC       attenuate insulin stimulation, mediated by FKBPs. Interacts mutually
CC       exclusive with EIF4A1 or EIF4A2. Binds to MKNK2 in nucleus (By
CC       similarity). Interacts with NGDN and PIWIL2. Component of the CYFIP1-
CC       EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1. Interacts
CC       directly with CYFIP1. Interacts with LIMD1, WTIP and AJUBA (By
CC       similarity). Interacts with APOBEC3G in an RNA-dependent manner.
CC       Interacts with LARP1 (By similarity). Interacts with CLOCK. Interacts
CC       with METTL3 (By similarity). Interacts with RBM24; this interaction
CC       prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly
CC       of translation initiation complex (By similarity).
CC       {ECO:0000250|UniProtKB:P06730, ECO:0000269|PubMed:10394359,
CC       ECO:0000269|PubMed:16705177, ECO:0000269|PubMed:18805096,
CC       ECO:0000269|PubMed:19114715, ECO:0000269|PubMed:22900038,
CC       ECO:0000269|PubMed:9200613}.
CC   -!- INTERACTION:
CC       Q7L576:CYFIP1 (xeno); NbExp=2; IntAct=EBI-2000006, EBI-1048143;
CC       Q7TMB8:Cyfip1; NbExp=5; IntAct=EBI-2000006, EBI-772928;
CC       Q60876:Eif4ebp1; NbExp=3; IntAct=EBI-2000006, EBI-398674;
CC       Q6NZJ6:Eif4g1; NbExp=7; IntAct=EBI-2000006, EBI-8175606;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000250}. Cytoplasm
CC       {ECO:0000269|PubMed:22900038}.
CC   -!- PTM: Phosphorylation increases the ability of the protein to bind to
CC       mRNA caps and to form the eIF4F complex. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the eukaryotic initiation factor 4E family.
CC       {ECO:0000305}.
DR   EMBL; M61731; AAA37545.1; -; mRNA.
DR   EMBL; BC010759; AAH10759.1; -; mRNA.
DR   EMBL; BC085087; AAH85087.1; -; mRNA.
DR   CCDS; CCDS38654.1; -.
DR   PIR; A34295; A34295.
DR   PIR; I49644; I49644.
DR   RefSeq; NP_031943.3; NM_007917.4.
DR   PDB; 1EJ1; X-ray; 2.20 A; A/B=28-217.
DR   PDB; 1EJ4; X-ray; 2.25 A; A=28-217.
DR   PDB; 1EJH; X-ray; 2.20 A; A/B/C/D=28-217.
DR   PDB; 1L8B; X-ray; 1.80 A; A/B=28-217.
DR   PDB; 5BXV; X-ray; 2.10 A; A/C=27-217.
DR   PDB; 5J5O; X-ray; 1.87 A; A/B/C/D=28-217.
DR   PDB; 5J5Y; X-ray; 1.75 A; A/B/C/D=28-217.
DR   PDB; 5M7V; X-ray; 1.74 A; A/B/C/D=28-217.
DR   PDB; 5M7W; X-ray; 1.97 A; A/B/C/D=28-217.
DR   PDB; 5M7X; X-ray; 1.68 A; A/B/C/D=28-217.
DR   PDB; 5M7Z; X-ray; 1.69 A; A/B/C/D=28-217.
DR   PDB; 5M80; X-ray; 2.12 A; A/B/C/D=28-217.
DR   PDB; 5M81; X-ray; 1.90 A; A/B/C/D=28-217.
DR   PDB; 5M83; X-ray; 1.86 A; A/B=28-217.
DR   PDB; 5M84; X-ray; 1.85 A; A/B=28-217.
DR   PDB; 5OSX; X-ray; 1.92 A; A/B/C/D=28-217.
DR   PDB; 6GKJ; X-ray; 2.07 A; A/B/C/D=28-217.
DR   PDB; 6GKK; X-ray; 1.86 A; A/B/C/D=28-217.
DR   PDB; 6GKL; X-ray; 2.20 A; A/B/C/D=28-217.
DR   PDBsum; 1EJ1; -.
DR   PDBsum; 1EJ4; -.
DR   PDBsum; 1EJH; -.
DR   PDBsum; 1L8B; -.
DR   PDBsum; 5BXV; -.
DR   PDBsum; 5J5O; -.
DR   PDBsum; 5J5Y; -.
DR   PDBsum; 5M7V; -.
DR   PDBsum; 5M7W; -.
DR   PDBsum; 5M7X; -.
DR   PDBsum; 5M7Z; -.
DR   PDBsum; 5M80; -.
DR   PDBsum; 5M81; -.
DR   PDBsum; 5M83; -.
DR   PDBsum; 5M84; -.
DR   PDBsum; 5OSX; -.
DR   PDBsum; 6GKJ; -.
DR   PDBsum; 6GKK; -.
DR   PDBsum; 6GKL; -.
DR   SMR; P63073; -.
DR   BioGrid; 199420; 12.
DR   DIP; DIP-42768N; -.
DR   IntAct; P63073; 12.
DR   MINT; P63073; -.
DR   STRING; 10090.ENSMUSP00000029803; -.
DR   BindingDB; P63073; -.
DR   ChEMBL; CHEMBL6148; -.
DR   iPTMnet; P63073; -.
DR   PhosphoSitePlus; P63073; -.
DR   REPRODUCTION-2DPAGE; P63073; -.
DR   EPD; P63073; -.
DR   jPOST; P63073; -.
DR   PaxDb; P63073; -.
DR   PeptideAtlas; P63073; -.
DR   PRIDE; P63073; -.
DR   Ensembl; ENSMUST00000029803; ENSMUSP00000029803; ENSMUSG00000028156.
DR   GeneID; 13684; -.
DR   KEGG; mmu:13684; -.
DR   UCSC; uc008rnn.1; mouse.
DR   CTD; 1977; -.
DR   MGI; MGI:95305; Eif4e.
DR   eggNOG; KOG1670; Eukaryota.
DR   eggNOG; COG5053; LUCA.
DR   GeneTree; ENSGT00940000154194; -.
DR   HOGENOM; HOG000186751; -.
DR   InParanoid; P63073; -.
DR   KO; K03259; -.
DR   OMA; NDIRPEW; -.
DR   PhylomeDB; P63073; -.
DR   TreeFam; TF101526; -.
DR   Reactome; R-MMU-1169408; ISG15 antiviral mechanism.
DR   Reactome; R-MMU-156827; L13a-mediated translational silencing of Ceruloplasmin expression.
DR   Reactome; R-MMU-159227; Transport of the SLBP independent Mature mRNA.
DR   Reactome; R-MMU-159230; Transport of the SLBP Dependant Mature mRNA.
DR   Reactome; R-MMU-159231; Transport of Mature mRNA Derived from an Intronless Transcript.
DR   Reactome; R-MMU-166208; mTORC1-mediated signalling.
DR   Reactome; R-MMU-429947; Deadenylation of mRNA.
DR   Reactome; R-MMU-72649; Translation initiation complex formation.
DR   Reactome; R-MMU-72662; Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S.
DR   Reactome; R-MMU-72702; Ribosomal scanning and start codon recognition.
DR   Reactome; R-MMU-72706; GTP hydrolysis and joining of the 60S ribosomal subunit.
DR   ChiTaRS; Eif4e; mouse.
DR   EvolutionaryTrace; P63073; -.
DR   PRO; PR:P63073; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; P63073; protein.
DR   Bgee; ENSMUSG00000028156; Expressed in 280 organ(s), highest expression level in testis.
DR   ExpressionAtlas; P63073; baseline and differential.
DR   Genevisible; P63073; MM.
DR   GO; GO:0033391; C:chromatoid body; IDA:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR   GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0016281; C:eukaryotic translation initiation factor 4F complex; ISS:UniProtKB.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0005845; C:mRNA cap binding complex; IDA:UniProtKB.
DR   GO; GO:0000932; C:P-body; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:AgBase.
DR   GO; GO:0098794; C:postsynapse; ISO:MGI.
DR   GO; GO:0099524; C:postsynaptic cytosol; ISO:MGI.
DR   GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR   GO; GO:0016442; C:RISC complex; ISO:MGI.
DR   GO; GO:0019899; F:enzyme binding; ISS:AgBase.
DR   GO; GO:0031370; F:eukaryotic initiation factor 4G binding; ISS:AgBase.
DR   GO; GO:0070491; F:repressing transcription factor binding; ISS:AgBase.
DR   GO; GO:0000340; F:RNA 7-methylguanosine cap binding; ISS:UniProtKB.
DR   GO; GO:0003743; F:translation initiation factor activity; IDA:UniProtKB.
DR   GO; GO:0045182; F:translation regulator activity; IDA:SynGO.
DR   GO; GO:0001662; P:behavioral fear response; IGI:MGI.
DR   GO; GO:0071549; P:cellular response to dexamethasone stimulus; IDA:MGI.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:MGI.
DR   GO; GO:0030324; P:lung development; IEA:Ensembl.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:MGI.
DR   GO; GO:0017148; P:negative regulation of translation; IMP:MGI.
DR   GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:MGI.
DR   GO; GO:0006417; P:regulation of translation; ISS:UniProtKB.
DR   GO; GO:0099578; P:regulation of translation at postsynapse, modulating synaptic transmission; IDA:SynGO.
DR   GO; GO:0019827; P:stem cell population maintenance; IMP:MGI.
DR   Gene3D; 3.30.760.10; -; 1.
DR   InterPro; IPR023398; TIF_eIF4e-like.
DR   InterPro; IPR001040; TIF_eIF_4E.
DR   InterPro; IPR019770; TIF_eIF_4E_CS.
DR   PANTHER; PTHR11960; PTHR11960; 1.
DR   Pfam; PF01652; IF4E; 1.
DR   SUPFAM; SSF55418; SSF55418; 1.
DR   PROSITE; PS00813; IF4E; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cytoplasm; Initiation factor; Phosphoprotein;
KW   Protein biosynthesis; Reference proteome; RNA-binding;
KW   Translation regulation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P06730"
FT   CHAIN           2..217
FT                   /note="Eukaryotic translation initiation factor 4E"
FT                   /id="PRO_0000193635"
FT   REGION          37..40
FT                   /note="EIF4EBP1/2/3 binding"
FT   REGION          56..57
FT                   /note="7-methylguanosine-containing mRNA cap binding"
FT   REGION          73..77
FT                   /note="EIF4EBP1/2/3 binding"
FT   REGION          102..103
FT                   /note="7-methylguanosine-containing mRNA cap binding"
FT   REGION          132..139
FT                   /note="EIF4EBP1/2/3 binding"
FT   REGION          157..162
FT                   /note="7-methylguanosine-containing mRNA cap binding"
FT   REGION          205..207
FT                   /note="7-methylguanosine-containing mRNA cap binding"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P06730"
FT   MOD_RES         22
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P06730"
FT   MOD_RES         209
FT                   /note="Phosphoserine; by PKC and MKNK2"
FT                   /evidence="ECO:0000269|PubMed:17689282"
FT   MUTAGEN         73
FT                   /note="W->A: Binding to CYFIP1 reduced by 70%."
FT                   /evidence="ECO:0000269|PubMed:18805096"
FT   CONFLICT        70
FT                   /note="E -> L (in Ref. 1; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   HELIX           31..33
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   STRAND          38..48
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   STRAND          52..54
FT                   /evidence="ECO:0000244|PDB:1L8B"
FT   HELIX           57..59
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   STRAND          60..68
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   HELIX           69..78
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   HELIX           82..84
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   STRAND          90..95
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   TURN            105..109
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   STRAND          111..116
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   HELIX           121..124
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   HELIX           126..138
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   TURN            139..142
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   HELIX           143..148
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   STRAND          149..155
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   STRAND          162..168
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   HELIX           173..187
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   TURN            191..193
FT                   /evidence="ECO:0000244|PDB:1EJH"
FT   STRAND          195..199
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   HELIX           200..203
FT                   /evidence="ECO:0000244|PDB:5M7X"
FT   STRAND          208..210
FT                   /evidence="ECO:0000244|PDB:1EJ1"
FT   STRAND          214..217
FT                   /evidence="ECO:0000244|PDB:5M7X"
SQ   SEQUENCE   217 AA;  25053 MW;  FC61D0FB337BCD8F CRC64;
     MATVEPETTP TTNPPPAEEE KTESNQEVAN PEHYIKHPLQ NRWALWFFKN DKSKTWQANL
     RLISKFDTVE DFWALYNHIQ LSSNLMPGCD YSLFKDGIEP MWEDEKNKRG GRWLITLNKQ
     QRRSDLDRFW LETLLCLIGE SFDDYSDDVC GAVVNVRAKG DKIAIWTTEC ENRDAVTHIG
     RVYKERLGLP PKIVIGYQSH ADTATKSGST TKNRFVV
//
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