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Database: UniProt
Entry: Q13541
LinkDB: Q13541
Original site: Q13541 
ID   4EBP1_HUMAN             Reviewed;         118 AA.
AC   Q13541; B2R502; D3DSW8; Q6IBN3;
DT   19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   07-OCT-2020, entry version 192.
DE   RecName: Full=Eukaryotic translation initiation factor 4E-binding protein 1;
DE            Short=4E-BP1;
DE            Short=eIF4E-binding protein 1;
DE   AltName: Full=Phosphorylated heat- and acid-stable protein regulated by insulin 1;
DE            Short=PHAS-I;
GN   Name=EIF4EBP1;
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 {ECO:0000312|EMBL:BAB18650.1};
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH EIF4E, AND
RP   PHOSPHORYLATION.
RC   TISSUE=Placenta;
RX   PubMed=7935836; DOI=10.1038/371762a0;
RA   Pause A., Belsham G.J., Gingras A.-C., Donze O., Lin T.-A.,
RA   Lawrence J.C. Jr., Sonenberg N.;
RT   "Insulin-dependent stimulation of protein synthesis by phosphorylation of a
RT   regulator of 5'-cap function.";
RL   Nature 371:762-767(1994).
RN   [2] {ECO:0000312|EMBL:BAB18650.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Ito M., Shichijo S., Tsuda N., Ochi M., Harashima N., Saito N., Itoh K.;
RT   "Identification of multiple genes and immunogenic epitopes of pancreatic
RT   cancer cells.";
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0000312|EMBL:BAB18650.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4] {ECO:0000312|EMBL:BAB18650.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [6] {ECO:0000312|EMBL:BAB18650.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Colon, and Lung {ECO:0000269|PubMed:15489334};
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   [8]
RP   PROTEIN SEQUENCE OF 2-13, AND ACETYLATION AT SER-2.
RC   TISSUE=Platelet;
RX   PubMed=12665801; DOI=10.1038/nbt810;
RA   Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA   Vandekerckhove J.;
RT   "Exploring proteomes and analyzing protein processing by mass spectrometric
RT   identification of sorted N-terminal peptides.";
RL   Nat. Biotechnol. 21:566-569(2003).
RN   [9]
RP   INTERACTION WITH EIF4E AND EIF4G.
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   [10]
RP   PHOSPHORYLATION BY MTOR.
RX   PubMed=9465032; DOI=10.1073/pnas.95.4.1432;
RA   Burnett P.E., Barrow R.K., Cohen N.A., Snyder S.H., Sabatini D.M.;
RT   "RAFT1 phosphorylation of the translational regulators p70 S6 kinase and
RT   4E-BP1.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:1432-1437(1998).
RN   [11]
RP   INTERACTION WITH RPTOR.
RX   PubMed=12150926; DOI=10.1016/s0092-8674(02)00833-4;
RA   Hara K., Maruki Y., Long X., Yoshino K., Oshiro N., Hidayat S.,
RA   Tokunaga C., Avruch J., Yonezawa K.;
RT   "Raptor, a binding partner of target of rapamycin (TOR), mediates TOR
RT   action.";
RL   Cell 110:177-189(2002).
RN   [12]
RP   INTERACTION WITH RPTOR, AND PHOSPHORYLATION AT THR-37; THR-46; SER-65 AND
RP   THR-70 BY MTOR.
RX   PubMed=12747827; DOI=10.1016/s0960-9822(03)00329-4;
RA   Schalm S.S., Fingar D.C., Sabatini D.M., Blenis J.;
RT   "TOS motif-mediated raptor binding regulates 4E-BP1 multisite
RT   phosphorylation and function.";
RL   Curr. Biol. 13:797-806(2003).
RN   [13]
RP   PHOSPHORYLATION AT SER-65; SER-101 AND SER-112, PROTEIN SEQUENCE, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=12588975; DOI=10.1128/mcb.23.5.1546-1557.2003;
RA   Wang X., Li W., Parra J.L., Beugnet A., Proud C.G.;
RT   "The C terminus of initiation factor 4E-binding protein 1 contains multiple
RT   regulatory features that influence its function and phosphorylation.";
RL   Mol. Cell. Biol. 23:1546-1557(2003).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT   networks.";
RL   Cell 127:635-648(2006).
RN   [15]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Prostate cancer;
RX   PubMed=17487921; DOI=10.1002/elps.200600782;
RA   Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT   "Toward a global characterization of the phosphoproteome in prostate cancer
RT   cells: identification of phosphoproteins in the LNCaP cell line.";
RL   Electrophoresis 28:2027-2034(2007).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic kidney;
RX   PubMed=17525332; DOI=10.1126/science.1140321;
RA   Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA   Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA   Gygi S.P., Elledge S.J.;
RT   "ATM and ATR substrate analysis reveals extensive protein networks
RT   responsive to DNA damage.";
RL   Science 316:1160-1166(2007).
RN   [17]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-50; THR-70 AND SER-101, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18220336; DOI=10.1021/pr0705441;
RA   Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT   phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [18]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37; THR-41; THR-46; THR-50;
RP   TYR-54; SER-65; THR-70 AND SER-83, AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [19]
RP   IDENTIFICATION BY MASS SPECTROMETRY [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   [20]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37 AND THR-46, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [21]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37 AND THR-70, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [22]
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   [23]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-70 AND SER-112, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [24]
RP   FUNCTION, INTERACTION WITH EIF4E, UBIQUITINATION AT LYS-57, PHOSPHORYLATION
RP   AT THR-37; THR-46; SER-65 AND THR-70, AND MUTAGENESIS OF THR-37; THR-46;
RP   LYS-57; 59-LEU-MET-60; SER-65; LYS-69; THR-70 AND LYS-105.
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   [25]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [26]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37; THR-41; SER-65; THR-70;
RP   SER-101 AND SER-112, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma, and 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   [27]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; THR-70 AND THR-77, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [28]
RP   PHOSPHORYLATION AT THR-37; THR-46; SER-65 AND THR-70.
RX   PubMed=29750193; DOI=10.1126/sciadv.aao5838;
RA   Nguyen J.T., Ray C., Fox A.L., Mendonca D.B., Kim J.K., Krebsbach P.H.;
RT   "Mammalian EAK-7 activates alternative mTOR signaling to regulate cell
RT   proliferation and migration.";
RL   Sci. Adv. 4:EAAO5838-EAAO5838(2018).
RN   [29]
RP   STRUCTURE BY NMR OF 4-118.
RX   PubMed=9684899; DOI=10.1002/pro.5560070720;
RA   Fletcher C.M., Wagner G.;
RT   "The interaction of eIF4E with 4E-BP1 is an induced fit to a completely
RT   disordered protein.";
RL   Protein Sci. 7:1639-1642(1998).
RN   [30]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 36-70 IN COMPLEX WITH EIF4E AND
RP   MRNA CAP ANALOG.
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   [31]
RP   X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 51-67 IN COMPLEX WITH EIF4E2 AND
RP   MRNA CAP ANALOG.
RX   PubMed=17368478; DOI=10.1016/j.jmb.2007.02.019;
RA   Rosettani P., Knapp S., Vismara M.-G., Rusconi L., Cameron A.D.;
RT   "Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP-
RT   bound and unliganded forms.";
RL   J. Mol. Biol. 368:691-705(2007).
RN   [32]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 51-64 IN COMPLEX WITH EIF4E AND
RP   MRNA CAP ANALOG.
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   [33] {ECO:0000244|PDB:4UED}
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 50-83 IN COMPLEX WITH EIF4E,
RP   INTERACTION WITH EIF4E, AND PHOSPHORYLATION AT SER-65 AND THR-70.
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: Repressor of translation initiation that regulates EIF4E
CC       activity by preventing its assembly into the eIF4F complex:
CC       hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds
CC       to EIF4E, leading to repress translation. In contrast,
CC       hyperphosphorylated form dissociates from EIF4E, allowing interaction
CC       between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation.
CC       Mediates the regulation of protein translation by hormones, growth
CC       factors and other stimuli that signal through the MAP kinase and mTORC1
CC       pathways. {ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:7935836}.
CC   -!- SUBUNIT: Hypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to
CC       interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or
CC       mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex
CC       allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation
CC       (PubMed:12150926, PubMed:16271312, PubMed:17368478, PubMed:17631896,
CC       PubMed:22578813, PubMed:7935836, PubMed:8521827, PubMed:25702871).
CC       Interacts (via TOS motif) with RPTOR; promoting phosphorylation by
CC       mTORC1 (PubMed:12747827). {ECO:0000269|PubMed:12150926,
CC       ECO:0000269|PubMed:12747827, ECO:0000269|PubMed:16271312,
CC       ECO:0000269|PubMed:17368478, ECO:0000269|PubMed:17631896,
CC       ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:25702871,
CC       ECO:0000269|PubMed:7935836, ECO:0000269|PubMed:8521827}.
CC   -!- INTERACTION:
CC       Q13541; Q9UKV8: AGO2; NbExp=2; IntAct=EBI-74090, EBI-528269;
CC       Q13541; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-74090, EBI-742054;
CC       Q13541; P06730: EIF4E; NbExp=27; IntAct=EBI-74090, EBI-73440;
CC       Q13541; A6NMX2: EIF4E1B; NbExp=3; IntAct=EBI-74090, EBI-18394358;
CC       Q13541; P25791-3: LMO2; NbExp=3; IntAct=EBI-74090, EBI-11959475;
CC       Q13541; P50221: MEOX1; NbExp=3; IntAct=EBI-74090, EBI-2864512;
CC       Q13541; P42345: MTOR; NbExp=2; IntAct=EBI-74090, EBI-359260;
CC       Q13541; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-74090, EBI-79165;
CC       Q13541; P78424: POU6F2; NbExp=3; IntAct=EBI-74090, EBI-12029004;
CC       Q13541; Q04864: REL; NbExp=3; IntAct=EBI-74090, EBI-307352;
CC       Q13541; Q04864-2: REL; NbExp=3; IntAct=EBI-74090, EBI-10829018;
CC       Q13541; Q8N122: RPTOR; NbExp=5; IntAct=EBI-74090, EBI-1567928;
CC       Q13541; P15884: TCF4; NbExp=3; IntAct=EBI-74090, EBI-533224;
CC       Q13541; Q8N720: ZNF655; NbExp=3; IntAct=EBI-74090, EBI-625509;
CC       Q13541; Q9JLN9: Mtor; Xeno; NbExp=2; IntAct=EBI-74090, EBI-1571628;
CC   -!- DOMAIN: The TOS motif mediates interaction with RPTOR, leading to
CC       promote phosphorylation by mTORC1 complex.
CC       {ECO:0000269|PubMed:12747827}.
CC   -!- PTM: Phosphorylated on serine and threonine residues in response to
CC       insulin, EGF and PDGF. Phosphorylation at Thr-37, Thr-46, Ser-65 and
CC       Thr-70, corresponding to the hyperphosphorylated form, is regulated by
CC       mTORC1 and abolishes binding to EIF4E. {ECO:0000269|PubMed:12588975,
CC       ECO:0000269|PubMed:12747827, ECO:0000269|PubMed:22578813,
CC       ECO:0000269|PubMed:7935836, ECO:0000269|PubMed:9465032}.
CC   -!- PTM: Ubiquitinated: when eIF4E levels are low, hypophosphorylated form
CC       is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation
CC       and serving as a homeostatic mechanism to maintain translation and
CC       prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated
CC       when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or
CC       associated with eIF4E. {ECO:0000269|PubMed:22578813}.
CC   -!- SIMILARITY: Belongs to the eIF4E-binding protein family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/EIF4EBP1ID40432ch8p12.html";
DR   EMBL; L36055; AAA62269.1; -; mRNA.
DR   EMBL; AB044548; BAB18650.1; -; mRNA.
DR   EMBL; BT007162; AAP35826.1; -; mRNA.
DR   EMBL; CR456769; CAG33050.1; -; mRNA.
DR   EMBL; AK312011; BAG34949.1; -; mRNA.
DR   EMBL; CH471080; EAW63341.1; -; Genomic_DNA.
DR   EMBL; CH471080; EAW63342.1; -; Genomic_DNA.
DR   EMBL; BC004459; AAH04459.1; -; mRNA.
DR   EMBL; BC058073; AAH58073.1; -; mRNA.
DR   CCDS; CCDS6100.1; -.
DR   PIR; S50866; S50866.
DR   RefSeq; NP_004086.1; NM_004095.3.
DR   PDB; 1EJ4; X-ray; 2.25 A; B=51-64.
DR   PDB; 1EJH; X-ray; 2.20 A; E/F/G/H=54-66.
DR   PDB; 1WKW; X-ray; 2.10 A; B=47-66.
DR   PDB; 2JGB; X-ray; 1.70 A; B=51-67.
DR   PDB; 2JGC; X-ray; 2.40 A; B=51-67.
DR   PDB; 2V8W; X-ray; 2.30 A; B/F=51-64.
DR   PDB; 2V8X; X-ray; 2.30 A; B/F=51-64.
DR   PDB; 2V8Y; X-ray; 2.10 A; B/F=51-64.
DR   PDB; 3HXG; X-ray; 2.10 A; C=51-67.
DR   PDB; 3HXI; X-ray; 1.80 A; C=51-67.
DR   PDB; 3M93; X-ray; 2.90 A; C=51-67.
DR   PDB; 3M94; X-ray; 2.05 A; C=51-67.
DR   PDB; 3U7X; X-ray; 2.10 A; C/D=47-66.
DR   PDB; 4UED; X-ray; 1.75 A; B=50-83.
DR   PDB; 5BXV; X-ray; 2.10 A; B/D=43-84.
DR   PDB; 5EKV; X-ray; 3.61 A; B/D=51-64.
DR   PDB; 5NVN; X-ray; 1.90 A; B/D=50-83.
DR   PDB; 5WBJ; X-ray; 3.00 A; T=99-118.
DR   PDB; 6BCU; EM; 3.43 A; X/Z=1-118.
DR   PDB; 6BCX; EM; 3.00 A; X/Z=1-118.
DR   PDBsum; 1EJ4; -.
DR   PDBsum; 1EJH; -.
DR   PDBsum; 1WKW; -.
DR   PDBsum; 2JGB; -.
DR   PDBsum; 2JGC; -.
DR   PDBsum; 2V8W; -.
DR   PDBsum; 2V8X; -.
DR   PDBsum; 2V8Y; -.
DR   PDBsum; 3HXG; -.
DR   PDBsum; 3HXI; -.
DR   PDBsum; 3M93; -.
DR   PDBsum; 3M94; -.
DR   PDBsum; 3U7X; -.
DR   PDBsum; 4UED; -.
DR   PDBsum; 5BXV; -.
DR   PDBsum; 5EKV; -.
DR   PDBsum; 5NVN; -.
DR   PDBsum; 5WBJ; -.
DR   PDBsum; 6BCU; -.
DR   PDBsum; 6BCX; -.
DR   BMRB; Q13541; -.
DR   SMR; Q13541; -.
DR   BioGRID; 108293; 54.
DR   DIP; DIP-30944N; -.
DR   ELM; Q13541; -.
DR   IntAct; Q13541; 26.
DR   MINT; Q13541; -.
DR   STRING; 9606.ENSP00000340691; -.
DR   ChEMBL; CHEMBL3351214; -.
DR   iPTMnet; Q13541; -.
DR   MetOSite; Q13541; -.
DR   PhosphoSitePlus; Q13541; -.
DR   BioMuta; EIF4EBP1; -.
DR   DMDM; 34921508; -.
DR   EPD; Q13541; -.
DR   jPOST; Q13541; -.
DR   MassIVE; Q13541; -.
DR   MaxQB; Q13541; -.
DR   PaxDb; Q13541; -.
DR   PeptideAtlas; Q13541; -.
DR   PRIDE; Q13541; -.
DR   ProteomicsDB; 59525; -.
DR   TopDownProteomics; Q13541; -.
DR   Antibodypedia; 3558; 1943 antibodies.
DR   DNASU; 1978; -.
DR   Ensembl; ENST00000338825; ENSP00000340691; ENSG00000187840.
DR   GeneID; 1978; -.
DR   KEGG; hsa:1978; -.
DR   UCSC; uc003xks.4; human.
DR   CTD; 1978; -.
DR   DisGeNET; 1978; -.
DR   EuPathDB; HostDB:ENSG00000187840.4; -.
DR   GeneCards; EIF4EBP1; -.
DR   HGNC; HGNC:3288; EIF4EBP1.
DR   HPA; ENSG00000187840; Tissue enhanced (pancreas, salivary gland).
DR   MIM; 602223; gene.
DR   neXtProt; NX_Q13541; -.
DR   OpenTargets; ENSG00000187840; -.
DR   PharmGKB; PA27715; -.
DR   eggNOG; ENOG502S4SY; Eukaryota.
DR   GeneTree; ENSGT00940000159932; -.
DR   HOGENOM; CLU_111706_0_0_1; -.
DR   InParanoid; Q13541; -.
DR   KO; K07205; -.
DR   OMA; MSGRCCH; -.
DR   OrthoDB; 1597535at2759; -.
DR   PhylomeDB; Q13541; -.
DR   TreeFam; TF101530; -.
DR   PathwayCommons; Q13541; -.
DR   Reactome; R-HSA-166208; mTORC1-mediated signalling.
DR   Reactome; R-HSA-72662; Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S.
DR   SignaLink; Q13541; -.
DR   SIGNOR; Q13541; -.
DR   BioGRID-ORCS; 1978; 23 hits in 871 CRISPR screens.
DR   ChiTaRS; EIF4EBP1; human.
DR   EvolutionaryTrace; Q13541; -.
DR   GeneWiki; EIF4EBP1; -.
DR   GenomeRNAi; 1978; -.
DR   Pharos; Q13541; Tbio.
DR   PRO; PR:Q13541; -.
DR   Proteomes; UP000005640; Unplaced.
DR   RNAct; Q13541; protein.
DR   Bgee; ENSG00000187840; Expressed in body of pancreas and 222 other tissues.
DR   Genevisible; Q13541; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:AgBase.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR   GO; GO:0099524; C:postsynaptic cytosol; IEA:Ensembl.
DR   GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR   GO; GO:0008190; F:eukaryotic initiation factor 4E binding; IDA:AgBase.
DR   GO; GO:0051721; F:protein phosphatase 2A binding; IEA:Ensembl.
DR   GO; GO:0030371; F:translation repressor activity; IDA:UniProtKB.
DR   GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR   GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR   GO; GO:0008286; P:insulin receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0002192; P:IRES-dependent translational initiation of linear mRNA; IEA:Ensembl.
DR   GO; GO:0030324; P:lung development; IEA:Ensembl.
DR   GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IEA:Ensembl.
DR   GO; GO:0045947; P:negative regulation of translational initiation; IDA:UniProtKB.
DR   GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR   GO; GO:1990928; P:response to amino acid starvation; IEA:Ensembl.
DR   GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR   GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR   GO; GO:0031929; P:TOR signaling; IDA:UniProtKB.
DR   DisProt; DP00028; -.
DR   IDEAL; IID00170; -.
DR   InterPro; IPR008606; EIF4EBP.
DR   InterPro; IPR037582; EIF4EBP1.
DR   PANTHER; PTHR12669:SF14; PTHR12669:SF14; 1.
DR   Pfam; PF05456; eIF_4EBP; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Direct protein sequencing; Isopeptide bond;
KW   Phosphoprotein; Protein synthesis inhibitor; Reference proteome;
KW   Translation regulation; Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000244|PubMed:22814378,
FT                   ECO:0000269|PubMed:12665801"
FT   CHAIN           2..118
FT                   /note="Eukaryotic translation initiation factor 4E-binding
FT                   protein 1"
FT                   /id="PRO_0000190513"
FT   MOTIF           54..60
FT                   /note="YXXXXLphi motif"
FT                   /evidence="ECO:0000250|UniProtKB:P70445"
FT   MOTIF           114..118
FT                   /note="TOS motif"
FT                   /evidence="ECO:0000269|PubMed:12747827"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000244|PubMed:22814378,
FT                   ECO:0000269|PubMed:12665801"
FT   MOD_RES         37
FT                   /note="Phosphothreonine; by MTOR"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:19690332, ECO:0000244|PubMed:20068231,
FT                   ECO:0000244|PubMed:23186163, ECO:0000269|PubMed:12747827,
FT                   ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:29750193"
FT   MOD_RES         41
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:23186163"
FT   MOD_RES         44
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q60876"
FT   MOD_RES         46
FT                   /note="Phosphothreonine; by MTOR"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:19690332, ECO:0000269|PubMed:12747827,
FT                   ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:29750193"
FT   MOD_RES         50
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:18220336,
FT                   ECO:0000244|PubMed:18669648"
FT   MOD_RES         54
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000244|PubMed:18669648"
FT   MOD_RES         65
FT                   /note="Phosphoserine; by DYRK2, MAPK1, MAPK3 and MTOR"
FT                   /evidence="ECO:0000244|PubMed:17081983,
FT                   ECO:0000244|PubMed:18669648, ECO:0000244|PubMed:23186163,
FT                   ECO:0000244|PubMed:24275569, ECO:0000269|PubMed:12588975,
FT                   ECO:0000269|PubMed:12747827, ECO:0000269|PubMed:22578813,
FT                   ECO:0000269|PubMed:25702871, ECO:0000269|PubMed:29750193"
FT   MOD_RES         70
FT                   /note="Phosphothreonine; by MTOR"
FT                   /evidence="ECO:0000244|PubMed:18220336,
FT                   ECO:0000244|PubMed:18669648, ECO:0000244|PubMed:20068231,
FT                   ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:23186163,
FT                   ECO:0000244|PubMed:24275569, ECO:0000269|PubMed:12747827,
FT                   ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:25702871,
FT                   ECO:0000269|PubMed:29750193"
FT   MOD_RES         77
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:24275569"
FT   MOD_RES         83
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648"
FT   MOD_RES         96
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q60876"
FT   MOD_RES         101
FT                   /note="Phosphoserine; by DYRK2"
FT                   /evidence="ECO:0000244|PubMed:18220336,
FT                   ECO:0000244|PubMed:23186163, ECO:0000269|PubMed:12588975"
FT   MOD_RES         112
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:17525332,
FT                   ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:23186163,
FT                   ECO:0000269|PubMed:12588975"
FT   CROSSLNK        57
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000305|PubMed:22578813"
FT   MUTAGEN         37
FT                   /note="T->A: Abolishes phosphorylation by MTOR and
FT                   increased ubiquitination by the BCR(KLHL25) complex; when
FT                   associated with A-46; A-65 and A-70."
FT                   /evidence="ECO:0000269|PubMed:22578813"
FT   MUTAGEN         46
FT                   /note="T->A: Abolishes phosphorylation by MTOR and
FT                   increased ubiquitination by the BCR(KLHL25) complex; when
FT                   associated with A-37; A-65 and A-70."
FT                   /evidence="ECO:0000269|PubMed:22578813"
FT   MUTAGEN         57
FT                   /note="K->R: Impaired ubiquitination by the BCR(KLHL25)
FT                   complex."
FT                   /evidence="ECO:0000269|PubMed:22578813"
FT   MUTAGEN         59..60
FT                   /note="LM->AA: Abolishes eIF4E-binding. Increased
FT                   ubiquitination by the BCR(KLHL25) complex."
FT                   /evidence="ECO:0000269|PubMed:22578813"
FT   MUTAGEN         65
FT                   /note="S->A: Abolishes phosphorylation by MTOR and
FT                   increased ubiquitination by the BCR(KLHL25) complex; when
FT                   associated with A-37; A-46 and A-70."
FT                   /evidence="ECO:0000269|PubMed:22578813"
FT   MUTAGEN         69
FT                   /note="K->R: Does not affect ubiquitination by the
FT                   BCR(KLHL25) complex."
FT                   /evidence="ECO:0000269|PubMed:22578813"
FT   MUTAGEN         70
FT                   /note="T->A: Abolishes phosphorylation by MTOR and
FT                   increased ubiquitination by the BCR(KLHL25) complex; when
FT                   associated with A-37; A-46 and A-65."
FT                   /evidence="ECO:0000269|PubMed:22578813"
FT   MUTAGEN         105
FT                   /note="K->R: Does not affect ubiquitination by the
FT                   BCR(KLHL25) complex."
FT                   /evidence="ECO:0000269|PubMed:22578813"
FT   HELIX           56..61
FT                   /evidence="ECO:0000244|PDB:2JGB"
FT   HELIX           62..64
FT                   /evidence="ECO:0000244|PDB:2JGB"
FT   HELIX           66..69
FT                   /evidence="ECO:0000244|PDB:4UED"
FT   TURN            79..82
FT                   /evidence="ECO:0000244|PDB:4UED"
SQ   SEQUENCE   118 AA;  12580 MW;  1682A6BA74132966 CRC64;
     MSGGSSCSQT PSRAIPATRR VVLGDGVQLP PGDYSTTPGG TLFSTTPGGT RIIYDRKFLM
     ECRNSPVTKT PPRDLPTIPG VTSPSSDEPP MEASQSHLRN SPEDKRAGGE ESQFEMDI
//
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