GenomeNet

Database: UniProt
Entry: P06730
LinkDB: P06730
Original site: P06730 
ID   IF4E_HUMAN              Reviewed;         217 AA.
AC   P06730; B7Z6V1; D6RCQ6; Q96E95;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 2.
DT   07-OCT-2020, entry version 224.
DE   RecName: Full=Eukaryotic translation initiation factor 4E {ECO:0000303|PubMed:1993647};
DE            Short=eIF-4E;
DE            Short=eIF4E;
DE   AltName: Full=eIF-4F 25 kDa subunit;
DE   AltName: Full=mRNA cap-binding protein {ECO:0000303|PubMed:3469651};
GN   Name=EIF4E {ECO:0000312|HGNC:HGNC:3287}; Synonyms=EIF4EL1, EIF4F;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Placenta;
RX   PubMed=3469651; DOI=10.1073/pnas.84.4.945;
RA   Rychlik W., Domier L.L., Gardner P.R., Hellmann G.M., Rhoads R.E.;
RT   "Amino acid sequence of the mRNA cap-binding protein from human tissues.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:945-949(1987).
RN   [2]
RP   ERRATUM OF PUBMED:3469651, AND SEQUENCE REVISION TO 108 AND 189.
RX   PubMed=1736299; DOI=10.1073/pnas.89.3.1148a;
RA   Rychlik W., Domier L.L., Gardner P.R., Hellmann G.M., Rhoads R.E.;
RL   Proc. Natl. Acad. Sci. U.S.A. 89:1148-1148(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Small intestine;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain, and Testis;
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   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-214 (ISOFORM 2).
RC   TISSUE=Myeloma;
RX   PubMed=16341674; DOI=10.1007/s00335-005-0075-2;
RA   Oh J.H., Yang J.O., Hahn Y., Kim M.R., Byun S.S., Jeon Y.J., Kim J.M.,
RA   Song K.S., Noh S.M., Kim S., Yoo H.S., Kim Y.S., Kim N.S.;
RT   "Transcriptome analysis of human gastric cancer.";
RL   Mamm. Genome 16:942-954(2005).
RN   [7]
RP   PARTIAL PROTEIN SEQUENCE.
RX   PubMed=1993647;
RA   Marino M.W., Feld L.J., Jaffe E.A., Pfeffer L.M., Han Y.-M., Donner D.B.;
RT   "Phosphorylation of the proto-oncogene product eukaryotic initiation factor
RT   4E is a common cellular response to tumor necrosis factor.";
RL   J. Biol. Chem. 266:2685-2688(1991).
RN   [8]
RP   MUTAGENESIS OF TRP-102; GLU-103; ASP-104 AND GLU-105.
RX   PubMed=1672854; DOI=10.1016/0014-5793(91)80294-d;
RA   Ueda H., Iyo H., Doi M., Inoue M., Ishida T., Morioka H., Tanaka T.,
RA   Nishikawa S., Uesugi S.;
RT   "Combination of Trp and Glu residues for recognition of mRNA cap structure.
RT   Analysis of m7G base recognition site of human cap binding protein (IF-4E)
RT   by site-directed mutagenesis.";
RL   FEBS Lett. 280:207-210(1991).
RN   [9]
RP   PHOSPHORYLATION.
RX   PubMed=3112145;
RA   Rychlik W., Russ M.A., Rhoads R.E.;
RT   "Phosphorylation site of eukaryotic initiation factor 4E.";
RL   J. Biol. Chem. 262:10434-10437(1987).
RN   [10]
RP   PHOSPHORYLATION, AND MUTAGENESIS OF SER-53.
RX   PubMed=8505316;
RA   Kaufman R.J., Murtha-Riel P., Pittman D.D., Davies M.V.;
RT   "Characterization of wild-type and Ser53 mutant eukaryotic initiation
RT   factor 4E overexpression in mammalian cells.";
RL   J. Biol. Chem. 268:11902-11909(1993).
RN   [11]
RP   PHOSPHORYLATION, AND MUTAGENESIS OF SER-53.
RX   PubMed=7590282; DOI=10.1016/0378-1119(95)00302-m;
RA   Zhang Y., Klein H.L., Schneider R.J.;
RT   "Role of Ser-53 phosphorylation in the activity of human translation
RT   initiation factor eIF-4E in mammalian and yeast cells.";
RL   Gene 163:283-288(1995).
RN   [12]
RP   PHOSPHORYLATION AT SER-209.
RX   PubMed=7782323; DOI=10.1074/jbc.270.24.14597;
RA   Joshi B., Cai A.L., Keiper B.D., Minich W.B., Mendez R., Beach C.M.,
RA   Stepinski J., Stolarski R., Darzynkiewicz E., Rhoads R.E.;
RT   "Phosphorylation of eukaryotic protein synthesis initiation factor 4E at
RT   Ser-209.";
RL   J. Biol. Chem. 270:14597-14603(1995).
RN   [13]
RP   PHOSPHORYLATION AT SER-209.
RX   PubMed=7665584; DOI=10.1074/jbc.270.37.21684;
RA   Flynn A., Proud C.G.;
RT   "Serine 209, not serine 53, is the major site of phosphorylation in
RT   initiation factor eIF-4E in serum-treated Chinese hamster ovary cells.";
RL   J. Biol. Chem. 270:21684-21688(1995).
RN   [14]
RP   INTERACTION WITH EIF4G AND EIF4EBP1.
RX   PubMed=8521827; DOI=10.1002/j.1460-2075.1995.tb00257.x;
RA   Haghighat A., Mader S., Pause A., Sonenberg N.;
RT   "Repression of cap-dependent translation by 4E-binding protein 1:
RT   competition with p220 for binding to eukaryotic initiation factor-4E.";
RL   EMBO J. 14:5701-5709(1995).
RN   [15]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH EIF4ENIF1.
RC   TISSUE=Fetal brain, and Placenta;
RX   PubMed=10856257; DOI=10.1093/emboj/19.12.3142;
RA   Dostie J., Ferraiuolo M., Pause A., Adam S.A., Sonenberg N.;
RT   "A novel shuttling protein, 4E-T, mediates the nuclear import of the mRNA
RT   5' cap-binding protein, eIF4E.";
RL   EMBO J. 19:3142-3156(2000).
RN   [16]
RP   PHOSPHORYLATION BY MKNK1.
RX   PubMed=9878069; DOI=10.1093/emboj/18.1.270;
RA   Pyronnet S., Imataka H., Gingras A.-C., Fukunaga R., Hunter T.,
RA   Sonenberg N.;
RT   "Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to
RT   phosphorylate eIF4E.";
RL   EMBO J. 18:270-279(1999).
RN   [17]
RP   INTERACTION WITH EIF4A1 AND EIF4A2.
RX   PubMed=11408474; DOI=10.1074/jbc.c100284200;
RA   Li W., Belsham G.J., Proud C.G.;
RT   "Eukaryotic initiation factors 4A (eIF4A) and 4G (eIF4G) mutually interact
RT   in a 1:1 ratio in vivo.";
RL   J. Biol. Chem. 276:29111-29115(2001).
RN   [18]
RP   PHOSPHORYLATION AT SER-209 BY MKNK2.
RX   PubMed=11154262; DOI=10.1128/mcb.21.3.743-754.2001;
RA   Scheper G.C., Morrice N.A., Kleijn M., Proud C.G.;
RT   "The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a
RT   eukaryotic initiation factor 4E kinase with high levels of basal activity
RT   in mammalian cells.";
RL   Mol. Cell. Biol. 21:743-754(2001).
RN   [19]
RP   INTERACTION WITH MKNK2.
RX   PubMed=12897141; DOI=10.1128/mcb.23.16.5692-5705.2003;
RA   Scheper G.C., Parra J.L., Wilson M., Van Kollenburg B., Vertegaal A.C.O.,
RA   Han Z.-G., Proud C.G.;
RT   "The N and C termini of the splice variants of the human mitogen-activated
RT   protein kinase-interacting kinase Mnk2 determine activity and
RT   localization.";
RL   Mol. Cell. Biol. 23:5692-5705(2003).
RN   [20]
RP   INTERACTION WITH APOBEC3G.
RX   PubMed=16699599; DOI=10.1371/journal.ppat.0020041;
RA   Wichroski M.J., Robb G.B., Rana T.M.;
RT   "Human retroviral host restriction factors APOBEC3G and APOBEC3F localize
RT   to mRNA processing bodies.";
RL   PLoS Pathog. 2:E41-E41(2006).
RN   [21]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH EIF4ENIF1.
RX   PubMed=16157702; DOI=10.1083/jcb.200504039;
RA   Ferraiuolo M.A., Basak S., Dostie J., Murray E.L., Schoenberg D.R.,
RA   Sonenberg N.;
RT   "A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA
RT   decay.";
RL   J. Cell Biol. 170:913-924(2005).
RN   [22]
RP   INTERACTION WITH DDX3X, AND MUTAGENESIS OF TRP-73.
RX   PubMed=17667941; DOI=10.1038/sj.onc.1210687;
RA   Shih J.W., Tsai T.Y., Chao C.H., Wu Lee Y.H.;
RT   "Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-
RT   dependent translation by acting as an eIF4E inhibitory protein.";
RL   Oncogene 27:700-714(2008).
RN   [23]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [24]
RP   INVOLVEMENT IN AUTS19, AND CHROMOSOMAL TRANSLOCATION.
RX   PubMed=19556253; DOI=10.1136/jmg.2009.066852;
RA   Neves-Pereira M., Mueller B., Massie D., Williams J.H., O'Brien P.C.,
RA   Hughes A., Shen S.B., Clair D.S., Miedzybrodzka Z.;
RT   "Deregulation of EIF4E: a novel mechanism for autism.";
RL   J. Med. Genet. 46:759-765(2009).
RN   [25]
RP   INTERACTION WITH LARP1.
RX   PubMed=20430826; DOI=10.1093/nar/gkq294;
RA   Burrows C., Abd Latip N., Lam S.J., Carpenter L., Sawicka K., Tzolovsky G.,
RA   Gabra H., Bushell M., Glover D.M., Willis A.E., Blagden S.P.;
RT   "The RNA binding protein Larp1 regulates cell division, apoptosis and cell
RT   migration.";
RL   Nucleic Acids Res. 38:5542-5553(2010).
RN   [26]
RP   INTERACTION WITH LASSA VIRUS PROTEIN Z (MICROBIAL INFECTION).
RX   PubMed=20212144; DOI=10.1073/pnas.0909877107;
RA   Volpon L., Osborne M.J., Capul A.A., de la Torre J.C., Borden K.L.;
RT   "Structural characterization of the Z RING-eIF4E complex reveals a distinct
RT   mode of control for eIF4E.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:5441-5446(2010).
RN   [27]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH LIMD1; WTIP AND AJUBA.
RX   PubMed=20616046; DOI=10.1073/pnas.0914987107;
RA   James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M.,
RA   Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J.,
RA   Longmore G.D., Bushell M., Sharp T.V.;
RT   "LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-
RT   mediated gene silencing.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010).
RN   [28]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [29]
RP   INTERACTION WITH DDX3X, AND SUBCELLULAR LOCATION.
RX   PubMed=21883093; DOI=10.1042/bj20110739;
RA   Shih J.W., Wang W.T., Tsai T.Y., Kuo C.Y., Li H.K., Wu Lee Y.H.;
RT   "Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1
RT   in stress granule assembly and stress response.";
RL   Biochem. J. 441:119-129(2012).
RN   [30]
RP   FUNCTION, AND MUTAGENESIS OF TRP-73.
RX   PubMed=22578813; DOI=10.1016/j.molcel.2012.04.004;
RA   Yanagiya A., Suyama E., Adachi H., Svitkin Y.V., Aza-Blanc P., Imataka H.,
RA   Mikami S., Martineau Y., Ronai Z.A., Sonenberg N.;
RT   "Translational homeostasis via the mRNA cap-binding protein, eIF4E.";
RL   Mol. Cell 46:847-858(2012).
RN   [31]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-22, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [32]
RP   INTERACTION WITH EIF4ENIF1.
RX   PubMed=23991149; DOI=10.1371/journal.pone.0072761;
RA   Kubacka D., Kamenska A., Broomhead H., Minshall N., Darzynkiewicz E.,
RA   Standart N.;
RT   "Investigating the consequences of eIF4E2 (4EHP) interaction with 4E-
RT   transporter on its cellular distribution in HeLa cells.";
RL   PLoS ONE 8:e72761-e72761(2013).
RN   [33]
RP   INTERACTION WITH EIF4EBP2.
RX   PubMed=24207126; DOI=10.1016/j.str.2013.08.030;
RA   Lukhele S., Bah A., Lin H., Sonenberg N., Forman-Kay J.D.;
RT   "Interaction of the eukaryotic initiation factor 4E with 4E-BP2 at a
RT   dynamic bipartite interface.";
RL   Structure 21:2186-2196(2013).
RN   [34]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EIF4ENIF1.
RX   PubMed=24335285; DOI=10.1093/nar/gkt1265;
RA   Kamenska A., Lu W.T., Kubacka D., Broomhead H., Minshall N., Bushell M.,
RA   Standart N.;
RT   "Human 4E-T represses translation of bound mRNAs and enhances microRNA-
RT   mediated silencing.";
RL   Nucleic Acids Res. 42:3298-3313(2014).
RN   [35]
RP   INTERACTION WITH EIF4EBP2.
RX   PubMed=25533957; DOI=10.1038/nature13999;
RA   Bah A., Vernon R.M., Siddiqui Z., Krzeminski M., Muhandiram R., Zhao C.,
RA   Sonenberg N., Kay L.E., Forman-Kay J.D.;
RT   "Folding of an intrinsically disordered protein by phosphorylation as a
RT   regulatory switch.";
RL   Nature 519:106-109(2015).
RN   [36]
RP   SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-209, INTERACTION WITH
RP   EIF4ENIF1, AND MUTAGENESIS OF SER-209.
RX   PubMed=25923732; DOI=10.1371/journal.pone.0123352;
RA   Martinez A., Sese M., Losa J.H., Robichaud N., Sonenberg N., Aasen T.,
RA   Ramon Y Cajal S.;
RT   "Phosphorylation of eIF4E confers resistance to cellular stress and DNA-
RT   damaging agents through an interaction with 4E-T: a rationale for novel
RT   therapeutic approaches.";
RL   PLoS ONE 10:e0123352-e0123352(2015).
RN   [37]
RP   INTERACTION WITH METTL3.
RX   PubMed=27117702; DOI=10.1016/j.molcel.2016.03.021;
RA   Lin S., Choe J., Du P., Triboulet R., Gregory R.I.;
RT   "The m(6)A methyltransferase METTL3 promotes translation in human cancer
RT   cells.";
RL   Mol. Cell 62:335-345(2016).
RN   [38]
RP   INTERACTION WITH DDX3X.
RX   PubMed=28733330; DOI=10.1042/bcj20170354;
RA   Copsey A.C., Cooper S., Parker R., Lineham E., Lapworth C., Jallad D.,
RA   Sweet S., Morley S.J.;
RT   "The helicase, DDX3X, interacts with poly(A)-binding protein 1 (PABP1) and
RT   caprin-1 at the leading edge of migrating fibroblasts and is required for
RT   efficient cell spreading.";
RL   Biochem. J. 474:3109-3120(2017).
RN   [39]
RP   INTERACTION WITH EIF4ENIF1.
RX   PubMed=28487484; DOI=10.1073/pnas.1701488114;
RA   Chapat C., Jafarnejad S.M., Matta-Camacho E., Hesketh G.G., Gelbart I.A.,
RA   Attig J., Gkogkas C.G., Alain T., Stern-Ginossar N., Fabian M.R.,
RA   Gingras A.C., Duchaine T.F., Sonenberg N.;
RT   "Cap-binding protein 4EHP effects translation silencing by microRNAs.";
RL   Proc. Natl. Acad. Sci. U.S.A. 114:5425-5430(2017).
RN   [40]
RP   INTERACTION WITH RBM24.
RX   PubMed=29358667; DOI=10.1038/s41418-017-0029-8;
RA   Zhang M., Zhang Y., Xu E., Mohibi S., de Anda D.M., Jiang Y., Zhang J.,
RA   Chen X.;
RT   "Rbm24, a target of p53, is necessary for proper expression of p53 and
RT   heart development.";
RL   Cell Death Differ. 25:1118-1130(2018).
RN   [41]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH MRNA CAP ANALOGS.
RX   PubMed=11879179; DOI=10.1042/0264-6021:3620539;
RA   Tomoo K., Shen X., Okabe K., Nozoe Y., Fukuhara S., Morino S., Ishida T.,
RA   Taniguchi T., Hasegawa H., Terashima A., Sasaki M., Katsuya Y.,
RA   Kitamura K., Miyoshi H., Ishikawa M., Miura K.;
RT   "Crystal structures of 7-methylguanosine 5'-triphosphate (m(7)GTP)- and
RT   P(1)-7-methylguanosine-P(3)-adenosine-5',5'-triphosphate (m(7)GpppA)-bound
RT   human full-length eukaryotic initiation factor 4E: biological importance of
RT   the C-terminal flexible region.";
RL   Biochem. J. 362:539-544(2002).
RN   [42]
RP   STRUCTURE BY NMR IN COMPLEX WITH EIF4G3 AND MRNA CAP ANALOGS.
RX   PubMed=12975586; DOI=10.1023/a:1025442322316;
RA   Miura T., Shiratori Y., Shimma N.;
RT   "Backbone resonance assignment of human eukaryotic translation initiation
RT   factor 4E (eIF4E) in complex with 7-methylguanosine diphosphate (m7GDP) and
RT   a 17-amino acid peptide derived from human eIF4GII.";
RL   J. Biomol. NMR 27:279-280(2003).
RN   [43]
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 27-217 IN COMPLEX WITH MRNA CAP
RP   ANALOG AND EIF4EBP1, FUNCTION, AND INTERACTION WITH EIF4EBP1; EIF4EBP2 AND
RP   EIF4EBP3.
RX   PubMed=16271312; DOI=10.1016/j.bbapap.2005.07.023;
RA   Tomoo K., Matsushita Y., Fujisaki H., Abiko F., Shen X., Taniguchi T.,
RA   Miyagawa H., Kitamura K., Miura K., Ishida T.;
RT   "Structural basis for mRNA cap-binding regulation of eukaryotic initiation
RT   factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal
RT   structural, and molecular dynamics simulation methods.";
RL   Biochim. Biophys. Acta 1753:191-208(2005).
RN   [44]
RP   STRUCTURE BY NMR, CLEAVAGE OF INITIATOR METHIONINE, MASS SPECTROMETRY, AND
RP   MUTAGENESIS OF LYS-119.
RX   PubMed=17036047; DOI=10.1038/sj.emboj.7601380;
RA   Volpon L., Osborne M.J., Topisirovic I., Siddiqui N., Borden K.L.B.;
RT   "Cap-free structure of eIF4E suggests a basis for conformational regulation
RT   by its ligands.";
RL   EMBO J. 25:5138-5149(2006).
RN   [45]
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH MRNA CAP ANALOGS,
RP   AND MASS SPECTROMETRY.
RX   PubMed=17631896; DOI=10.1016/j.jmb.2007.06.033;
RA   Brown C.J., McNae I., Fischer P.M., Walkinshaw M.D.;
RT   "Crystallographic and mass spectrometric characterisation of eIF4E with N7-
RT   alkylated cap derivatives.";
RL   J. Mol. Biol. 372:7-15(2007).
RN   [46]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 27-217 IN COMPLEX WITH EIF4EBP2,
RP   AND INTERACTION WITH EIF4EBP2.
RX   PubMed=21661078; DOI=10.1002/psc.1384;
RA   Fukuyo A., In Y., Ishida T., Tomoo K.;
RT   "Structural scaffold for eIF4E binding selectivity of 4E-BP isoforms:
RT   crystal structure of eIF4E binding region of 4E-BP2 and its comparison with
RT   that of 4E-BP1.";
RL   J. Pept. Sci. 17:650-657(2011).
RN   [47] {ECO:0000244|PDB:4UED}
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 36-217 IN COMPLEX WITH EIF4EBP1,
RP   AND INTERACTION WITH EIF4EBP1.
RX   PubMed=25702871; DOI=10.1016/j.molcel.2015.01.017;
RA   Peter D., Igreja C., Weber R., Wohlbold L., Weiler C., Ebertsch L.,
RA   Weichenrieder O., Izaurralde E.;
RT   "Molecular architecture of 4E-BP translational inhibitors bound to eIF4E.";
RL   Mol. Cell 57:1074-1087(2015).
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 (PubMed:16271312, PubMed:22578813). In addition to
CC       its role in translation initiation, also acts as a regulator of
CC       translation and stability in the cytoplasm (PubMed:24335285). Component
CC       of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and
CC       mediates translational repression: in the complex, EIF4E mediates the
CC       binding to the mRNA cap (By similarity). Component of a multiprotein
CC       complex that sequesters and represses translation of proneurogenic
CC       factors during neurogenesis (By similarity). In P-bodies, component of
CC       a complex that mediates the storage of translationally inactive mRNAs
CC       in the cytoplasm and prevents their degradation (PubMed:24335285). May
CC       play an important role in spermatogenesis through translational
CC       regulation of stage-specific mRNAs during germ cell development (By
CC       similarity). {ECO:0000250|UniProtKB:P63073,
CC       ECO:0000250|UniProtKB:P63074, ECO:0000269|PubMed:16271312,
CC       ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:24335285}.
CC   -!- SUBUNIT: eIF4F is a multi-subunit complex, the composition of which
CC       varies with external and internal environmental conditions
CC       (PubMed:11408474, PubMed:11879179, PubMed:16271312, PubMed:17631896).
CC       It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3
CC       (PubMed:8521827, PubMed:11408474, PubMed:11879179, PubMed:12975586).
CC       EIF4E is also known to interact with other partners (PubMed:8521827,
CC       PubMed:11408474, PubMed:11879179, PubMed:12975586). Interacts with
CC       EIF4ENIF1/4E-T; promotes recruitment to P-bodies and import into the
CC       nucleus (PubMed:10856257, PubMed:16157702, PubMed:23991149,
CC       PubMed:24335285, PubMed:28487484). 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 (PubMed:8521827,
CC       PubMed:16271312, PubMed:21661078, PubMed:24207126, PubMed:25533957,
CC       PubMed:25702871). Interacts mutually exclusive with EIF4A1 or EIF4A2
CC       (PubMed:11408474). Interacts with NGDN and PIWIL2 (By similarity).
CC       Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and
CC       FMR1 (By similarity). Interacts directly with CYFIP1 (By similarity).
CC       Interacts with CLOCK (By similarity). Binds to MKNK2 in nucleus
CC       (PubMed:12897141). Interacts with LIMD1, WTIP and AJUBA
CC       (PubMed:20616046). Interacts with APOBEC3G in an RNA-dependent manner
CC       (PubMed:16699599). Interacts with LARP1 (PubMed:20430826). Interacts
CC       with METTL3 (PubMed:27117702). Interacts with RBM24; this interaction
CC       prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly
CC       of translation initiation complex (PubMed:29358667). Interacts with
CC       DDX3X; interaction is direct and in an RNA-independent manner; this
CC       interaction enhances EIF4E cap-binding ability and is required for the
CC       repression of cap-dependent translation and the increase of IRES-
CC       mediated translation (PubMed:17667941, PubMed:21883093,
CC       PubMed:28733330). DDX3X competes with EIF4G1 for interaction with EIF4E
CC       (PubMed:17667941, PubMed:21883093). {ECO:0000250|UniProtKB:P63073,
CC       ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:11408474,
CC       ECO:0000269|PubMed:11879179, ECO:0000269|PubMed:12897141,
CC       ECO:0000269|PubMed:12975586, ECO:0000269|PubMed:16157702,
CC       ECO:0000269|PubMed:16271312, ECO:0000269|PubMed:16699599,
CC       ECO:0000269|PubMed:17631896, ECO:0000269|PubMed:17667941,
CC       ECO:0000269|PubMed:20430826, ECO:0000269|PubMed:20616046,
CC       ECO:0000269|PubMed:21661078, ECO:0000269|PubMed:21883093,
CC       ECO:0000269|PubMed:23991149, ECO:0000269|PubMed:24207126,
CC       ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:25533957,
CC       ECO:0000269|PubMed:25702871, ECO:0000269|PubMed:27117702,
CC       ECO:0000269|PubMed:28487484, ECO:0000269|PubMed:28733330,
CC       ECO:0000269|PubMed:29358667, ECO:0000269|PubMed:8521827}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with Lassa virus Z protein.
CC       {ECO:0000269|PubMed:20212144}.
CC   -!- INTERACTION:
CC       P06730; Q13541: EIF4EBP1; NbExp=27; IntAct=EBI-73440, EBI-74090;
CC       P06730; Q13542: EIF4EBP2; NbExp=12; IntAct=EBI-73440, EBI-935137;
CC       P06730; O60516: EIF4EBP3; NbExp=9; IntAct=EBI-73440, EBI-746950;
CC       P06730; Q9NRA8: EIF4ENIF1; NbExp=10; IntAct=EBI-73440, EBI-301024;
CC       P06730; Q04637: EIF4G1; NbExp=9; IntAct=EBI-73440, EBI-73711;
CC       P06730; O43432-1: EIF4G3; NbExp=2; IntAct=EBI-73440, EBI-15841003;
CC       P06730; Q04743: EMX2; NbExp=4; IntAct=EBI-73440, EBI-399831;
CC       P06730; Q8TEQ6: GEMIN5; NbExp=3; IntAct=EBI-73440, EBI-443630;
CC       P06730; Q63ZY3: KANK2; NbExp=7; IntAct=EBI-73440, EBI-2556193;
CC       P06730; P42704: LRPPRC; NbExp=6; IntAct=EBI-73440, EBI-1050853;
CC       P06730; P11940: PABPC1; NbExp=5; IntAct=EBI-73440, EBI-81531;
CC       P06730; P67775: PPP2CA; NbExp=2; IntAct=EBI-73440, EBI-712311;
CC       P06730; P63165: SUMO1; NbExp=5; IntAct=EBI-73440, EBI-80140;
CC       P06730; P48775: TDO2; NbExp=4; IntAct=EBI-73440, EBI-743494;
CC       P06730; P14373: TRIM27; NbExp=5; IntAct=EBI-73440, EBI-719493;
CC       P06730; Q5T124: UBXN11; NbExp=3; IntAct=EBI-73440, EBI-746004;
CC       P06730; O70552: Btg4; Xeno; NbExp=4; IntAct=EBI-73440, EBI-16204405;
CC       P06730; Q60809: Cnot7; Xeno; NbExp=2; IntAct=EBI-73440, EBI-2104739;
CC       P06730; O73557: Z; Xeno; NbExp=3; IntAct=EBI-73440, EBI-15840965;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:16157702,
CC       ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:24335285,
CC       ECO:0000269|PubMed:25923732}. Cytoplasm {ECO:0000269|PubMed:10856257,
CC       ECO:0000269|PubMed:21883093}. Cytoplasm, Stress granule
CC       {ECO:0000269|PubMed:21883093}. Nucleus {ECO:0000269|PubMed:10856257}.
CC       Note=Interaction with EIF4ENIF1/4E-T is required for localization to
CC       processing bodies (P-bodies) (PubMed:16157702, PubMed:24335285,
CC       PubMed:25923732). Imported in the nucleus via interaction with
CC       EIF4ENIF1/4E-T via a piggy-back mechanism (PubMed:10856257).
CC       {ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:16157702,
CC       ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:25923732}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P06730-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P06730-2; Sequence=VSP_042014;
CC       Name=3;
CC         IsoId=P06730-3; Sequence=VSP_043591;
CC   -!- PTM: Phosphorylation increases the ability of the protein to bind to
CC       mRNA caps and to form the eIF4F complex. {ECO:0000269|PubMed:11154262,
CC       ECO:0000269|PubMed:3112145, ECO:0000269|PubMed:7590282,
CC       ECO:0000269|PubMed:7665584, ECO:0000269|PubMed:7782323,
CC       ECO:0000269|PubMed:8505316, ECO:0000269|PubMed:9878069}.
CC   -!- MASS SPECTROMETRY: Mass=24964.3; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:17036047};
CC   -!- MASS SPECTROMETRY: Mass=24960; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:17631896};
CC   -!- DISEASE: Autism 19 (AUTS19) [MIM:615091]: A complex multifactorial,
CC       pervasive developmental disorder characterized by impairments in
CC       reciprocal social interaction and communication, restricted and
CC       stereotyped patterns of interests and activities, and the presence of
CC       developmental abnormalities by 3 years of age. Most individuals with
CC       autism also manifest moderate mental retardation.
CC       {ECO:0000269|PubMed:19556253}. Note=Disease susceptibility is
CC       associated with variations affecting the gene represented in this
CC       entry. A heterozygous single-nucleotide insertion has been found in
CC       families affected by autism. The variant results in increased promoter
CC       activity and is involved in disease pathogenesis through EIF4E
CC       deregulation (PubMed:19556253). {ECO:0000269|PubMed:19556253}.
CC   -!- DISEASE: Note=A chromosomal aberration involving EIF4E has been found
CC       in a patient with classic autism. Translocation t(45)(q23q31.3). The
CC       breakpoint on chromosome 4 is located 56 kb downstream of EIF4E
CC       (PubMed:19556253). {ECO:0000269|PubMed:19556253}.
CC   -!- SIMILARITY: Belongs to the eukaryotic initiation factor 4E family.
CC       {ECO:0000305}.
CC   -!- CAUTION: Was originally thought to be phosphorylated on Ser-53
CC       (PubMed:3112145); this was later shown to be wrong (PubMed:7665584).
CC       {ECO:0000305|PubMed:3112145, ECO:0000305|PubMed:7665584}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/EIF4EID40431ch4q23.html";
DR   EMBL; M15353; AAC13647.1; -; mRNA.
DR   EMBL; AK300982; BAH13387.1; -; mRNA.
DR   EMBL; AC019131; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC093836; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC012611; AAH12611.1; -; mRNA.
DR   EMBL; BC035166; AAH35166.1; -; mRNA.
DR   EMBL; BC043226; AAH43226.1; -; mRNA.
DR   EMBL; BM849222; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS34031.1; -. [P06730-1]
DR   CCDS; CCDS47109.1; -. [P06730-3]
DR   CCDS; CCDS54779.1; -. [P06730-2]
DR   PIR; A26411; A26411.
DR   RefSeq; NP_001124150.1; NM_001130678.2. [P06730-3]
DR   RefSeq; NP_001124151.1; NM_001130679.2. [P06730-2]
DR   RefSeq; NP_001317946.1; NM_001331017.1.
DR   RefSeq; NP_001959.1; NM_001968.4. [P06730-1]
DR   PDB; 1IPB; X-ray; 2.00 A; A=1-217.
DR   PDB; 1IPC; X-ray; 2.00 A; A=1-217.
DR   PDB; 1WKW; X-ray; 2.10 A; A=27-217.
DR   PDB; 2GPQ; NMR; -; A=1-217.
DR   PDB; 2V8W; X-ray; 2.30 A; A/E=1-217.
DR   PDB; 2V8X; X-ray; 2.30 A; A/E=1-217.
DR   PDB; 2V8Y; X-ray; 2.10 A; A/E=1-217.
DR   PDB; 2W97; X-ray; 2.29 A; A/B=1-217.
DR   PDB; 3AM7; X-ray; 2.20 A; A=27-217.
DR   PDB; 3TF2; X-ray; 2.10 A; A/B/C/D=1-217.
DR   PDB; 3U7X; X-ray; 2.10 A; A/B=1-217.
DR   PDB; 4AZA; X-ray; 2.16 A; A/C=1-217.
DR   PDB; 4BEA; X-ray; 2.57 A; A=1-217.
DR   PDB; 4DT6; X-ray; 2.60 A; A=1-217.
DR   PDB; 4DUM; X-ray; 2.95 A; A=1-217.
DR   PDB; 4TPW; X-ray; 1.50 A; A/B=28-217.
DR   PDB; 4TQB; X-ray; 1.59 A; A/B=28-217.
DR   PDB; 4TQC; X-ray; 1.80 A; A/B=28-217.
DR   PDB; 4UED; X-ray; 1.75 A; A=36-217.
DR   PDB; 5EHC; X-ray; 2.40 A; A=1-217.
DR   PDB; 5EI3; X-ray; 1.71 A; A=1-217.
DR   PDB; 5EIR; X-ray; 2.69 A; A=1-217.
DR   PDB; 5EKV; X-ray; 3.61 A; A/C=1-217.
DR   PDB; 5GW6; X-ray; 1.97 A; A=23-217.
DR   PDB; 5T46; X-ray; 1.53 A; A/C=1-217.
DR   PDB; 5ZJY; X-ray; 1.59 A; A=28-217.
DR   PDB; 5ZJZ; X-ray; 1.67 A; A=28-217.
DR   PDB; 5ZK5; X-ray; 2.25 A; A=28-217.
DR   PDB; 5ZK7; X-ray; 2.12 A; A/B=28-217.
DR   PDB; 5ZK9; X-ray; 1.76 A; A=28-217.
DR   PDB; 5ZML; X-ray; 1.80 A; A=27-217.
DR   PDBsum; 1IPB; -.
DR   PDBsum; 1IPC; -.
DR   PDBsum; 1WKW; -.
DR   PDBsum; 2GPQ; -.
DR   PDBsum; 2V8W; -.
DR   PDBsum; 2V8X; -.
DR   PDBsum; 2V8Y; -.
DR   PDBsum; 2W97; -.
DR   PDBsum; 3AM7; -.
DR   PDBsum; 3TF2; -.
DR   PDBsum; 3U7X; -.
DR   PDBsum; 4AZA; -.
DR   PDBsum; 4BEA; -.
DR   PDBsum; 4DT6; -.
DR   PDBsum; 4DUM; -.
DR   PDBsum; 4TPW; -.
DR   PDBsum; 4TQB; -.
DR   PDBsum; 4TQC; -.
DR   PDBsum; 4UED; -.
DR   PDBsum; 5EHC; -.
DR   PDBsum; 5EI3; -.
DR   PDBsum; 5EIR; -.
DR   PDBsum; 5EKV; -.
DR   PDBsum; 5GW6; -.
DR   PDBsum; 5T46; -.
DR   PDBsum; 5ZJY; -.
DR   PDBsum; 5ZJZ; -.
DR   PDBsum; 5ZK5; -.
DR   PDBsum; 5ZK7; -.
DR   PDBsum; 5ZK9; -.
DR   PDBsum; 5ZML; -.
DR   BMRB; P06730; -.
DR   SMR; P06730; -.
DR   BioGRID; 108292; 72.
DR   CORUM; P06730; -.
DR   DIP; DIP-22N; -.
DR   ELM; P06730; -.
DR   IntAct; P06730; 50.
DR   MINT; P06730; -.
DR   BindingDB; P06730; -.
DR   ChEMBL; CHEMBL4848; -.
DR   DrugBank; DB01960; 7-methyl-7,8-dihydroguanosine-5'-diphosphate.
DR   DrugBank; DB01649; 7-methyl-GpppA.
DR   DrugBank; DB02716; 7-methyl-guanosine-5'-triphosphate.
DR   DrugBank; DB05165; LY2275796.
DR   DrugBank; DB08217; S-[(1-Hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl] methanesulfonothioate.
DR   DrugCentral; P06730; -.
DR   iPTMnet; P06730; -.
DR   MetOSite; P06730; -.
DR   PhosphoSitePlus; P06730; -.
DR   SwissPalm; P06730; -.
DR   BioMuta; EIF4E; -.
DR   DMDM; 1352435; -.
DR   OGP; P06730; -.
DR   REPRODUCTION-2DPAGE; IPI00027485; -.
DR   EPD; P06730; -.
DR   jPOST; P06730; -.
DR   MassIVE; P06730; -.
DR   MaxQB; P06730; -.
DR   PeptideAtlas; P06730; -.
DR   PRIDE; P06730; -.
DR   ProteomicsDB; 51914; -. [P06730-1]
DR   ProteomicsDB; 51915; -. [P06730-2]
DR   ProteomicsDB; 51916; -. [P06730-3]
DR   TopDownProteomics; P06730-1; -. [P06730-1]
DR   Antibodypedia; 3421; 937 antibodies.
DR   DNASU; 1977; -.
DR   Ensembl; ENST00000280892; ENSP00000280892; ENSG00000151247. [P06730-3]
DR   Ensembl; ENST00000450253; ENSP00000389624; ENSG00000151247. [P06730-1]
DR   Ensembl; ENST00000505992; ENSP00000425561; ENSG00000151247. [P06730-2]
DR   GeneID; 1977; -.
DR   KEGG; hsa:1977; -.
DR   UCSC; uc003hue.3; human. [P06730-1]
DR   CTD; 1977; -.
DR   DisGeNET; 1977; -.
DR   EuPathDB; HostDB:ENSG00000151247.12; -.
DR   GeneCards; EIF4E; -.
DR   HGNC; HGNC:3287; EIF4E.
DR   HPA; ENSG00000151247; Low tissue specificity.
DR   MalaCards; EIF4E; -.
DR   MIM; 133440; gene.
DR   MIM; 615091; phenotype.
DR   neXtProt; NX_P06730; -.
DR   OpenTargets; ENSG00000151247; -.
DR   Orphanet; 106; NON RARE IN EUROPE: Autism.
DR   PharmGKB; PA27714; -.
DR   GeneTree; ENSGT00940000154194; -.
DR   HOGENOM; CLU_043552_1_1_1; -.
DR   InParanoid; P06730; -.
DR   KO; K03259; -.
DR   OMA; NDIRPEW; -.
DR   OrthoDB; 1394271at2759; -.
DR   PhylomeDB; P06730; -.
DR   TreeFam; TF101526; -.
DR   PathwayCommons; P06730; -.
DR   Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR   Reactome; R-HSA-156827; L13a-mediated translational silencing of Ceruloplasmin expression.
DR   Reactome; R-HSA-159227; Transport of the SLBP independent Mature mRNA.
DR   Reactome; R-HSA-159230; Transport of the SLBP Dependant Mature mRNA.
DR   Reactome; R-HSA-159231; Transport of Mature mRNA Derived from an Intronless Transcript.
DR   Reactome; R-HSA-166208; mTORC1-mediated signalling.
DR   Reactome; R-HSA-429947; Deadenylation of mRNA.
DR   Reactome; R-HSA-72649; Translation initiation complex formation.
DR   Reactome; R-HSA-72662; Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S.
DR   Reactome; R-HSA-72702; Ribosomal scanning and start codon recognition.
DR   Reactome; R-HSA-72706; GTP hydrolysis and joining of the 60S ribosomal subunit.
DR   SignaLink; P06730; -.
DR   SIGNOR; P06730; -.
DR   BioGRID-ORCS; 1977; 716 hits in 881 CRISPR screens.
DR   ChiTaRS; EIF4E; human.
DR   EvolutionaryTrace; P06730; -.
DR   GeneWiki; EIF4E; -.
DR   GenomeRNAi; 1977; -.
DR   Pharos; P06730; Tchem.
DR   PRO; PR:P06730; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; P06730; protein.
DR   Bgee; ENSG00000151247; Expressed in calcaneal tendon and 236 other tissues.
DR   ExpressionAtlas; P06730; baseline and differential.
DR   Genevisible; P06730; HS.
DR   GO; GO:0033391; C:chromatoid body; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IDA:AgBase.
DR   GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR   GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0016281; C:eukaryotic translation initiation factor 4F complex; IDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0005845; C:mRNA cap binding complex; IDA:UniProtKB.
DR   GO; GO:0000932; C:P-body; IDA:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:AgBase.
DR   GO; GO:0099524; C:postsynaptic cytosol; IEA:Ensembl.
DR   GO; GO:0016442; C:RISC complex; IDA:MGI.
DR   GO; GO:0019899; F:enzyme binding; IDA:AgBase.
DR   GO; GO:0031370; F:eukaryotic initiation factor 4G binding; IDA:AgBase.
DR   GO; GO:0070491; F:repressing transcription factor binding; IDA:AgBase.
DR   GO; GO:0000340; F:RNA 7-methylguanosine cap binding; IDA:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0000339; F:RNA cap binding; TAS:ProtInc.
DR   GO; GO:0003743; F:translation initiation factor activity; IDA:UniProtKB.
DR   GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR   GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR   GO; GO:0030324; P:lung development; IEA:Ensembl.
DR   GO; GO:0006406; P:mRNA export from nucleus; TAS:Reactome.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR   GO; GO:0017148; P:negative regulation of translation; IEA:Ensembl.
DR   GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR   GO; GO:0006417; P:regulation of translation; IDA:UniProtKB.
DR   GO; GO:0006405; P:RNA export from nucleus; TAS:Reactome.
DR   GO; GO:0019827; P:stem cell population maintenance; IEA:Ensembl.
DR   GO; GO:0006413; P:translational initiation; TAS:Reactome.
DR   GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.760.10; -; 1.
DR   IDEAL; IID00341; -.
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; Alternative splicing; Autism;
KW   Autism spectrum disorder; Chromosomal rearrangement; Cytoplasm;
KW   Direct protein sequencing; Host-virus interaction; Initiation factor;
KW   Nucleus; Phosphoprotein; Protein biosynthesis; Reference proteome;
KW   RNA-binding; Translation regulation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000244|PubMed:19413330,
FT                   ECO:0000269|PubMed:17036047"
FT   CHAIN           2..217
FT                   /note="Eukaryotic translation initiation factor 4E"
FT                   /id="PRO_0000193634"
FT   REGION          37..40
FT                   /note="EIF4EBP1/2/3 binding"
FT                   /evidence="ECO:0000269|PubMed:16271312"
FT   REGION          56..57
FT                   /note="7-methylguanosine-containing mRNA cap binding"
FT                   /evidence="ECO:0000269|PubMed:11879179,
FT                   ECO:0000269|PubMed:12975586, ECO:0000269|PubMed:16271312"
FT   REGION          73..77
FT                   /note="EIF4EBP1/2/3 binding"
FT                   /evidence="ECO:0000269|PubMed:16271312"
FT   REGION          102..103
FT                   /note="7-methylguanosine-containing mRNA cap binding"
FT                   /evidence="ECO:0000269|PubMed:11879179,
FT                   ECO:0000269|PubMed:12975586, ECO:0000269|PubMed:16271312"
FT   REGION          132..139
FT                   /note="EIF4EBP1/2/3 binding"
FT                   /evidence="ECO:0000269|PubMed:16271312"
FT   REGION          157..162
FT                   /note="7-methylguanosine-containing mRNA cap binding"
FT                   /evidence="ECO:0000269|PubMed:11879179,
FT                   ECO:0000269|PubMed:12975586, ECO:0000269|PubMed:16271312"
FT   REGION          205..207
FT                   /note="7-methylguanosine-containing mRNA cap binding"
FT                   /evidence="ECO:0000269|PubMed:11879179,
FT                   ECO:0000269|PubMed:12975586, ECO:0000269|PubMed:16271312"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000244|PubMed:19413330"
FT   MOD_RES         22
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         209
FT                   /note="Phosphoserine; by PKC and MKNK2"
FT                   /evidence="ECO:0000269|PubMed:11154262,
FT                   ECO:0000269|PubMed:25923732, ECO:0000269|PubMed:7665584,
FT                   ECO:0000269|PubMed:7782323"
FT   VAR_SEQ         1..6
FT                   /note="MATVEP -> MLDLTSRGQVGTSRRMAEAACSAHFL (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_043591"
FT   VAR_SEQ         133
FT                   /note="T -> TRWDLAMLPRLVSNFWPQVILPLQPPKVLELQ (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:16341674"
FT                   /id="VSP_042014"
FT   MUTAGEN         53
FT                   /note="S->A,D: No effect on phosphorylation level nor
FT                   incorporation into eIF4F complex."
FT                   /evidence="ECO:0000269|PubMed:7590282,
FT                   ECO:0000269|PubMed:8505316"
FT   MUTAGEN         73
FT                   /note="W->A: Abolishes binding to EIF4EBP1. Impairs
FT                   interaction with DDX3X."
FT                   /evidence="ECO:0000269|PubMed:17667941,
FT                   ECO:0000269|PubMed:22578813"
FT   MUTAGEN         102
FT                   /note="W->L: Decrease in mRNA cap binding; when associated
FT                   with A-105."
FT                   /evidence="ECO:0000269|PubMed:1672854"
FT   MUTAGEN         103
FT                   /note="E->A: No effect."
FT                   /evidence="ECO:0000269|PubMed:1672854"
FT   MUTAGEN         104
FT                   /note="D->A: No effect."
FT                   /evidence="ECO:0000269|PubMed:1672854"
FT   MUTAGEN         105
FT                   /note="E->A: Decrease in mRNA cap binding; when associated
FT                   with L-102."
FT                   /evidence="ECO:0000269|PubMed:1672854"
FT   MUTAGEN         119
FT                   /note="K->A: Higher affinity for EIF4G1."
FT                   /evidence="ECO:0000269|PubMed:17036047"
FT   MUTAGEN         209
FT                   /note="S->A: Abolished resistance to cellular stress and
FT                   DNA-damaging agents."
FT                   /evidence="ECO:0000269|PubMed:25923732"
FT   MUTAGEN         209
FT                   /note="S->D: Phosphomimetic mutant; confers resistance to
FT                   cellular stress and DNA-damaging agents."
FT                   /evidence="ECO:0000269|PubMed:25923732"
FT   CONFLICT        127
FT                   /note="D -> N (in Ref. 5; AAH12611)"
FT                   /evidence="ECO:0000305"
FT   HELIX           31..33
FT                   /evidence="ECO:0000244|PDB:5EI3"
FT   STRAND          38..49
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   STRAND          50..52
FT                   /evidence="ECO:0000244|PDB:5ZJZ"
FT   HELIX           56..59
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   STRAND          60..68
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   HELIX           69..82
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   STRAND          89..95
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   STRAND          100..103
FT                   /evidence="ECO:0000244|PDB:2GPQ"
FT   TURN            105..109
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   STRAND          111..116
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   HELIX           119..122
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   TURN            123..125
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   HELIX           126..138
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   TURN            139..142
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   HELIX           143..148
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   STRAND          149..155
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   STRAND          162..168
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   HELIX           173..187
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   STRAND          191..193
FT                   /evidence="ECO:0000244|PDB:4TQC"
FT   STRAND          196..199
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   HELIX           200..204
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   STRAND          205..207
FT                   /evidence="ECO:0000244|PDB:3AM7"
FT   TURN            208..210
FT                   /evidence="ECO:0000244|PDB:4TPW"
FT   STRAND          214..216
FT                   /evidence="ECO:0000244|PDB:4TPW"
SQ   SEQUENCE   217 AA;  25097 MW;  B869B8DE615E699D CRC64;
     MATVEPETTP TPNPPTTEEE KTESNQEVAN PEHYIKHPLQ NRWALWFFKN DKSKTWQANL
     RLISKFDTVE DFWALYNHIQ LSSNLMPGCD YSLFKDGIEP MWEDEKNKRG GRWLITLNKQ
     QRRSDLDRFW LETLLCLIGE SFDDYSDDVC GAVVNVRAKG DKIAIWTTEC ENREAVTHIG
     RVYKERLGLP PKIVIGYQSH ADTATKSGST TKNRFVV
//
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