IF4E_HUMAN
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 03-AUG-2022, entry version 232.
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; DOI=10.1016/s0021-9258(18)49896-1;
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; DOI=10.1016/s0021-9258(18)60978-0;
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; DOI=10.1016/s0021-9258(19)50285-x;
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 INTERACTION WITH POTATO VIRUS Y VPG (MICROBIA INFECTION).
RX PubMed=31712417; DOI=10.1073/pnas.1904752116;
RA Coutinho de Oliveira L., Volpon L., Rahardjo A.K., Osborne M.J.,
RA Culjkovic-Kraljacic B., Trahan C., Oeffinger M., Kwok B.H., Borden K.L.B.;
RT "Structural studies of the eIF4E-VPg complex reveal a direct competition
RT for capped RNA: Implications for translation.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:24056-24065(2019).
RN [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48] {ECO:0007744|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). Interacts with BTG4 and CNOT7 (By
CC similarity). {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 -!- SUBUNIT: (Microbial infection) Interacts (via cap-binding region) with
CC potato virus Y VPg; this interaction mediates the translation of the
CC VPg-viral RNA conjugates and interferes with the cellular EIF4E-
CC dependent mRNA export and translation. {ECO:0000269|PubMed:31712417}.
CC -!- INTERACTION:
CC P06730; Q13541: EIF4EBP1; NbExp=29; IntAct=EBI-73440, EBI-74090;
CC P06730; Q13542: EIF4EBP2; NbExp=13; IntAct=EBI-73440, EBI-935137;
CC P06730; O60516: EIF4EBP3; NbExp=9; IntAct=EBI-73440, EBI-746950;
CC P06730; Q9NRA8: EIF4ENIF1; NbExp=12; IntAct=EBI-73440, EBI-301024;
CC P06730; Q04637: EIF4G1; NbExp=10; IntAct=EBI-73440, EBI-73711;
CC P06730; O43432: EIF4G3; NbExp=3; IntAct=EBI-73440, EBI-464766;
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 intellectual disability.
CC {ECO:0000269|PubMed:19556253}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC A heterozygous single-nucleotide insertion has been found in families
CC affected by autism. The variant results in increased promoter activity
CC and is involved in disease pathogenesis through EIF4E deregulation
CC (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";
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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 PDB; 7D6Y; X-ray; 1.67 A; A=1-217.
DR PDB; 7D8B; X-ray; 2.46 A; A/C=1-217.
DR PDB; 7MEU; X-ray; 1.91 A; A/B=26-217.
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 PDBsum; 7D6Y; -.
DR PDBsum; 7D8B; -.
DR PDBsum; 7MEU; -.
DR AlphaFoldDB; P06730; -.
DR BMRB; P06730; -.
DR SMR; P06730; -.
DR BioGRID; 108292; 96.
DR ComplexPortal; CPX-2666; Eukaryotic translation initiation factor 4F, EIF4A1 and EIF4G1 variant.
DR ComplexPortal; CPX-5634; Eukaryotic translation initiation factor 4F, EIF4A2 and EIF4G1 variant.
DR ComplexPortal; CPX-5635; Eukaryotic translation initiation factor 4F, EIF4A1 and EIF4G3 variant.
DR ComplexPortal; CPX-5636; Eukaryotic translation initiation factor 4F, EIF4A2 and EIF4G3 variant.
DR CORUM; P06730; -.
DR DIP; DIP-22N; -.
DR ELM; P06730; -.
DR IntAct; P06730; 72.
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 GlyGen; P06730; 2 sites, 1 O-linked glycan (2 sites).
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; 1000 antibodies from 45 providers.
DR DNASU; 1977; -.
DR Ensembl; ENST00000280892.10; ENSP00000280892.6; ENSG00000151247.13. [P06730-3]
DR Ensembl; ENST00000450253.7; ENSP00000389624.2; ENSG00000151247.13. [P06730-1]
DR Ensembl; ENST00000505992.1; ENSP00000425561.1; ENSG00000151247.13. [P06730-2]
DR GeneID; 1977; -.
DR KEGG; hsa:1977; -.
DR MANE-Select; ENST00000450253.7; ENSP00000389624.2; NM_001968.5; NP_001959.1.
DR UCSC; uc003hue.3; human. [P06730-1]
DR CTD; 1977; -.
DR DisGeNET; 1977; -.
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 VEuPathDB; HostDB:ENSG00000151247; -.
DR GeneTree; ENSGT00940000154194; -.
DR HOGENOM; CLU_043552_1_1_1; -.
DR InParanoid; P06730; -.
DR OMA; XLYNHIQ; -.
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; 738 hits in 1056 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 sperm and 198 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:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
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:0140297; F:DNA-binding transcription factor binding; IDA:AgBase.
DR GO; GO:0019899; F:enzyme binding; IDA:AgBase.
DR GO; GO:0031370; F:eukaryotic initiation factor 4G 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:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0017148; P:negative regulation of translation; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; 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:0099578; P:regulation of translation at postsynapse, modulating synaptic transmission; IEA:Ensembl.
DR GO; GO:0019827; P:stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0006413; P:translational initiation; IC:ComplexPortal.
DR DisProt; DP02399; -.
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:0000269|PubMed:17036047,
FT ECO:0007744|PubMed:19413330"
FT CHAIN 2..217
FT /note="Eukaryotic translation initiation factor 4E"
FT /id="PRO_0000193634"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 37..40
FT /note="EIF4EBP1/2/3 binding"
FT /evidence="ECO:0000269|PubMed:16271312"
FT REGION 73..77
FT /note="EIF4EBP1/2/3 binding"
FT /evidence="ECO:0000269|PubMed:16271312"
FT REGION 132..139
FT /note="EIF4EBP1/2/3 binding"
FT /evidence="ECO:0000269|PubMed:16271312"
FT BINDING 56..57
FT /ligand="mRNA"
FT /ligand_id="ChEBI:CHEBI:33699"
FT /ligand_part="N(7)-methylguanosine 5'-triphosphate group"
FT /ligand_part_id="ChEBI:CHEBI:74429"
FT /ligand_part_note="m7GTP residue in mRNA cap"
FT /evidence="ECO:0000269|PubMed:11879179,
FT ECO:0000269|PubMed:12975586, ECO:0000269|PubMed:16271312"
FT BINDING 102..103
FT /ligand="mRNA"
FT /ligand_id="ChEBI:CHEBI:33699"
FT /ligand_part="N(7)-methylguanosine 5'-triphosphate group"
FT /ligand_part_id="ChEBI:CHEBI:74429"
FT /ligand_part_note="m7GTP residue in mRNA cap"
FT /evidence="ECO:0000269|PubMed:11879179,
FT ECO:0000269|PubMed:12975586, ECO:0000269|PubMed:16271312"
FT BINDING 157..162
FT /ligand="mRNA"
FT /ligand_id="ChEBI:CHEBI:33699"
FT /ligand_part="N(7)-methylguanosine 5'-triphosphate group"
FT /ligand_part_id="ChEBI:CHEBI:74429"
FT /ligand_part_note="m7GTP residue in mRNA cap"
FT /evidence="ECO:0000269|PubMed:11879179,
FT ECO:0000269|PubMed:12975586, ECO:0000269|PubMed:16271312"
FT BINDING 205..207
FT /ligand="mRNA"
FT /ligand_id="ChEBI:CHEBI:33699"
FT /ligand_part="N(7)-methylguanosine 5'-triphosphate group"
FT /ligand_part_id="ChEBI:CHEBI:74429"
FT /ligand_part_note="m7GTP residue in mRNA cap"
FT /evidence="ECO:0000269|PubMed:11879179,
FT ECO:0000269|PubMed:12975586, ECO:0000269|PubMed:16271312"
FT SITE 159
FT /note="(Microbial infection) Interaction with potato virus
FT Y VPg"
FT /evidence="ECO:0000269|PubMed:31712417"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 22
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|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:0007829|PDB:5EI3"
FT STRAND 38..49
FT /evidence="ECO:0007829|PDB:4TPW"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:5ZJZ"
FT HELIX 56..59
FT /evidence="ECO:0007829|PDB:4TPW"
FT STRAND 60..68
FT /evidence="ECO:0007829|PDB:4TPW"
FT HELIX 69..82
FT /evidence="ECO:0007829|PDB:4TPW"
FT STRAND 89..95
FT /evidence="ECO:0007829|PDB:4TPW"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:2GPQ"
FT TURN 105..109
FT /evidence="ECO:0007829|PDB:4TPW"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:4TPW"
FT HELIX 119..122
FT /evidence="ECO:0007829|PDB:4TPW"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:4TPW"
FT HELIX 126..138
FT /evidence="ECO:0007829|PDB:4TPW"
FT TURN 139..142
FT /evidence="ECO:0007829|PDB:4TPW"
FT HELIX 143..148
FT /evidence="ECO:0007829|PDB:4TPW"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:4TPW"
FT STRAND 162..168
FT /evidence="ECO:0007829|PDB:4TPW"
FT HELIX 173..187
FT /evidence="ECO:0007829|PDB:4TPW"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:4TQC"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:4TPW"
FT HELIX 200..204
FT /evidence="ECO:0007829|PDB:4TPW"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:3AM7"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:4TPW"
FT STRAND 214..216
FT /evidence="ECO:0007829|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
