true2003-09-192024-03-272094EBP1_HUMANInsulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function.Pause A.Belsham G.J.Gingras A.-C.Donze O.Lin T.-A.Lawrence J.C. Jr.Sonenberg N.doi:10.1038/371762a01994Nature371762-767NUCLEOTIDE SEQUENCE [MRNA]FUNCTIONINTERACTION WITH EIF4EPHOSPHORYLATIONPlacentaIdentification of multiple genes and immunogenic epitopes of pancreatic cancer cells.Ito M.Shichijo S.Tsuda N.Ochi M.Harashima N.Saito N.Itoh K.2000-06EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [MRNA]Cloning of human full-length CDSs in BD Creator(TM) system donor vector.Kalnine N.Chen X.Rolfs A.Halleck A.Hines L.Eisenstein S.Koundinya M.Raphael J.Moreira D.Kelley T.LaBaer J.Lin Y.Phelan M.Farmer A.2003-05EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).Ebert L.Schick M.Neubert P.Schatten R.Henze S.Korn B.2004-06EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]Complete sequencing and characterization of 21,243 full-length human cDNAs.Ota T.Suzuki Y.Nishikawa T.Otsuki T.Sugiyama T.Irie R.Wakamatsu A.Hayashi K.Sato H.Nagai K.Kimura K.Makita H.Sekine M.Obayashi M.Nishi T.Shibahara T.Tanaka T.Ishii S.Yamamoto J.Saito K.Kawai Y.Isono Y.Nakamura Y.Nagahari K.Murakami K.Yasuda T.Iwayanagi T.Wagatsuma M.Shiratori A.Sudo H.Hosoiri T.Kaku Y.Kodaira H.Kondo H.Sugawara M.Takahashi M.Kanda K.Yokoi T.Furuya T.Kikkawa E.Omura Y.Abe K.Kamihara K.Katsuta N.Sato K.Tanikawa M.Yamazaki M.Ninomiya K.Ishibashi T.Yamashita H.Murakawa K.Fujimori K.Tanai H.Kimata M.Watanabe M.Hiraoka S.Chiba Y.Ishida S.Ono Y.Takiguchi S.Watanabe S.Yosida M.Hotuta T.Kusano J.Kanehori K.Takahashi-Fujii A.Hara H.Tanase T.-O.Nomura Y.Togiya S.Komai F.Hara R.Takeuchi K.Arita M.Imose N.Musashino K.Yuuki H.Oshima A.Sasaki N.Aotsuka S.Yoshikawa Y.Matsunawa H.Ichihara T.Shiohata N.Sano S.Moriya S.Momiyama H.Satoh N.Takami S.Terashima Y.Suzuki O.Nakagawa S.Senoh A.Mizoguchi H.Goto Y.Shimizu F.Wakebe H.Hishigaki H.Watanabe T.Sugiyama A.Takemoto M.Kawakami B.Yamazaki M.'Watanabe K.Kumagai A.Itakura S.Fukuzumi Y.Fujimori Y.Komiyama M.Tashiro H.Tanigami A.Fujiwara T.Ono T.Yamada K.Fujii Y.Ozaki K.Hirao M.Ohmori Y.Kawabata A.Hikiji T.Kobatake N.Inagaki H.Ikema Y.Okamoto S.Okitani R.Kawakami T.Noguchi S.Itoh T.Shigeta K.Senba T.Matsumura K.Nakajima Y.Mizuno T.Morinaga M.Sasaki M.Togashi T.Oyama M.Hata H.Watanabe M.'Komatsu T.Mizushima-Sugano J.Satoh T.Shirai Y.Takahashi Y.Nakagawa K.Okumura K.Nagase T.Nomura N.Kikuchi H.Masuho Y.Yamashita R.Nakai K.Yada T.Nakamura Y.'Ohara O.Isogai T.Sugano S.doi:10.1038/ng12852004Nat. Genet.3640-45NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]BrainMural R.J.Istrail S.Sutton G.G.Florea L.Halpern A.L.Mobarry C.M.Lippert R.Walenz B.Shatkay H.Dew I.Miller J.R.Flanigan M.J.Edwards N.J.Bolanos R.Fasulo D.Halldorsson B.V.Hannenhalli S.Turner R.Yooseph S.Lu F.Nusskern D.R.Shue B.C.Zheng X.H.Zhong F.Delcher A.L.Huson D.H.Kravitz S.A.Mouchard L.Reinert K.Remington K.A.Clark A.G.Waterman M.S.Eichler E.E.Adams M.D.Hunkapiller M.W.Myers E.W.Venter J.C.2005-09EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).The MGC Project Teamdoi:10.1101/gr.25965042004Genome Res.142121-2127NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]ColonLungExploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.Gevaert K.Goethals M.Martens L.Van Damme J.Staes A.Thomas G.R.Vandekerckhove J.doi:10.1038/nbt8102003Nat. Biotechnol.21566-569PROTEIN SEQUENCE OF 2-13ACETYLATION AT SER-2PlateletRepression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E.Haghighat A.Mader S.Pause A.Sonenberg N.doi:10.1002/j.1460-2075.1995.tb00257.x1995EMBO J.145701-5709INTERACTION WITH EIF4E AND EIF4GRAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1.Burnett P.E.Barrow R.K.Cohen N.A.Snyder S.H.Sabatini D.M.doi:10.1073/pnas.95.4.14321998Proc. Natl. Acad. Sci. U.S.A.951432-1437PHOSPHORYLATION BY MTORRaptor, a binding partner of target of rapamycin (TOR), mediates TOR action.Hara K.Maruki Y.Long X.Yoshino K.Oshiro N.Hidayat S.Tokunaga C.Avruch J.Yonezawa K.doi:10.1016/s0092-8674(02)00833-42002Cell110177-189INTERACTION WITH RPTORTOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function.Schalm S.S.Fingar D.C.Sabatini D.M.Blenis J.doi:10.1016/s0960-9822(03)00329-42003Curr. Biol.13797-806INTERACTION WITH RPTORPHOSPHORYLATION AT THR-37; THR-46; SER-65 AND THR-70 BY MTORThe C terminus of initiation factor 4E-binding protein 1 contains multiple regulatory features that influence its function and phosphorylation.Wang X.Li W.Parra J.L.Beugnet A.Proud C.G.doi:10.1128/mcb.23.5.1546-1557.20032003Mol. Cell. Biol.231546-1557PHOSPHORYLATION AT SER-65; SER-101 AND SER-112PROTEIN SEQUENCEIDENTIFICATION BY MASS SPECTROMETRYGlobal, in vivo, and site-specific phosphorylation dynamics in signaling networks.Olsen J.V.Blagoev B.Gnad F.Macek B.Kumar C.Mortensen P.Mann M.doi:10.1016/j.cell.2006.09.0262006Cell127635-648PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Cervix carcinomaToward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line.Giorgianni F.Zhao Y.Desiderio D.M.Beranova-Giorgianni S.doi:10.1002/elps.2006007822007Electrophoresis282027-2034IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Prostate cancerATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.Matsuoka S.Ballif B.A.Smogorzewska A.McDonald E.R. IIIHurov K.E.Luo J.Bakalarski C.E.Zhao Z.Solimini N.Lerenthal Y.Shiloh Y.Gygi S.P.Elledge S.J.doi:10.1126/science.11403212007Science3161160-1166PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Embryonic kidneyCombining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.Cantin G.T.Yi W.Lu B.Park S.K.Xu T.Lee J.-D.Yates J.R. IIIdoi:10.1021/pr07054412008J. Proteome Res.71346-1351PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-50; THR-70 AND SER-101IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]A quantitative atlas of mitotic phosphorylation.Dephoure N.Zhou C.Villen J.Beausoleil S.A.Bakalarski C.E.Elledge S.J.Gygi S.P.doi:10.1073/pnas.08051391052008Proc. Natl. Acad. Sci. U.S.A.10510762-10767PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37; THR-41; THR-46; THR-50; TYR-54; SER-65; THR-70 AND SER-83IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.Gauci S.Helbig A.O.Slijper M.Krijgsveld J.Heck A.J.Mohammed S.doi:10.1021/ac90043092009Anal. Chem.814493-4501IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.Mayya V.Lundgren D.H.Hwang S.-I.Rezaul K.Wu L.Eng J.K.Rodionov V.Han D.K.doi:10.1126/scisignal.20000072009Sci. Signal.2RA46PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37 AND THR-46IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Leukemic T-cellQuantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.Olsen J.V.Vermeulen M.Santamaria A.Kumar C.Miller M.L.Jensen L.J.Gnad F.Cox J.Jensen T.S.Nigg E.A.Brunak S.Mann M.doi:10.1126/scisignal.20004752010Sci. Signal.3RA3PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37 AND THR-70IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Initial characterization of the human central proteome.Burkard T.R.Planyavsky M.Kaupe I.Breitwieser F.P.Buerckstuemmer T.Bennett K.L.Superti-Furga G.Colinge J.doi:10.1186/1752-0509-5-172011BMC Syst. Biol.517IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.Rigbolt K.T.Prokhorova T.A.Akimov V.Henningsen J.Johansen P.T.Kratchmarova I.Kassem M.Mann M.Olsen J.V.Blagoev B.doi:10.1126/scisignal.20015702011Sci. Signal.4RS3PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-70 AND SER-112IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]4E-BP3 regulates eIF4E-mediated nuclear mRNA export and interacts with replication protein A2.Chen C.C.Lee J.C.Chang M.C.doi:10.1016/j.febslet.2012.05.0592012FEBS Lett.5862260-2266FUNCTIONSUBCELLULAR LOCATIONTranslational homeostasis via the mRNA cap-binding protein, eIF4E.Yanagiya A.Suyama E.Adachi H.Svitkin Y.V.Aza-Blanc P.Imataka H.Mikami S.Martineau Y.Ronai Z.A.Sonenberg N.doi:10.1016/j.molcel.2012.04.0042012Mol. Cell46847-858FUNCTIONINTERACTION WITH EIF4EUBIQUITINATION AT LYS-57PHOSPHORYLATION AT THR-37; THR-46; SER-65 AND THR-70MUTAGENESIS OF THR-37; THR-46; LYS-57; 59-LEU-MET-60; SER-65; LYS-69; THR-70 AND LYS-105N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.Van Damme P.Lasa M.Polevoda B.Gazquez C.Elosegui-Artola A.Kim D.S.De Juan-Pardo E.Demeyer K.Hole K.Larrea E.Timmerman E.Prieto J.Arnesen T.Sherman F.Gevaert K.Aldabe R.doi:10.1073/pnas.12103031092012Proc. Natl. Acad. Sci. U.S.A.10912449-12454ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Toward a comprehensive characterization of a human cancer cell phosphoproteome.Zhou H.Di Palma S.Preisinger C.Peng M.Polat A.N.Heck A.J.Mohammed S.doi:10.1021/pr300630k2013J. Proteome Res.12260-271PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37; THR-41; SER-65; THR-70; SER-101 AND SER-112IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]ErythroleukemiaCharacterization of the Raptor/4E-BP1 interaction by chemical cross-linking coupled with mass spectrometry analysis.Coffman K.Yang B.Lu J.Tetlow A.L.Pelliccio E.Lu S.Guo D.C.Tang C.Dong M.Q.Tamanoi F.doi:10.1074/jbc.m113.4820672014J. Biol. Chem.2894723-4734INTERACTION WITH RPTORPHOSPHORYLATION BY MTORAn enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.Bian Y.Song C.Cheng K.Dong M.Wang F.Huang J.Sun D.Wang L.Ye M.Zou H.doi:10.1016/j.jprot.2013.11.0142014J. Proteomics96253-262PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; THR-70 AND THR-77IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]LiverMammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration.Nguyen J.T.Ray C.Fox A.L.Mendonca D.B.Kim J.K.Krebsbach P.H.doi:10.1126/sciadv.aao58382018Sci. Adv.4EAAO5838PHOSPHORYLATION AT THR-37; THR-46; SER-65 AND THR-70The interaction of eIF4E with 4E-BP1 is an induced fit to a completely disordered protein.Fletcher C.M.Wagner G.doi:10.1002/pro.55600707201998Protein Sci.71639-1642STRUCTURE BY NMR OF 4-118Structural basis for mRNA cap-binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods.Tomoo K.Matsushita Y.Fujisaki H.Abiko F.Shen X.Taniguchi T.Miyagawa H.Kitamura K.Miura K.Ishida T.doi:10.1016/j.bbapap.2005.07.0232005Biochim. Biophys. Acta1753191-208X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 36-70 IN COMPLEX WITH EIF4E AND MRNA CAP ANALOGStructures of the human eIF4E homologous protein, h4EHP, in its m7GTP-bound and unliganded forms.Rosettani P.Knapp S.Vismara M.-G.Rusconi L.Cameron A.D.doi:10.1016/j.jmb.2007.02.0192007J. Mol. Biol.368691-705X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 51-67 IN COMPLEX WITH EIF4E2 AND MRNA CAP ANALOGCrystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives.Brown C.J.McNae I.Fischer P.M.Walkinshaw M.D.doi:10.1016/j.jmb.2007.06.0332007J. Mol. Biol.3727-15X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 51-64 IN COMPLEX WITH EIF4E AND MRNA CAP ANALOGMolecular architecture of 4E-BP translational inhibitors bound to eIF4E.Peter D.Igreja C.Weber R.Wohlbold L.Weiler C.Ebertsch L.Weichenrieder O.Izaurralde E.doi:10.1016/j.molcel.2015.01.0172015Mol. Cell571074-1087X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 50-83 IN COMPLEX WITH EIF4EINTERACTION WITH EIF4EPHOSPHORYLATION AT SER-65 AND THR-70Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.Yang H.Jiang X.Li B.Yang H.J.Miller M.Yang A.Dhar A.Pavletich N.P.doi:10.1038/nature250232017Nature552368-373STRUCTURE BY ELECTRON MICROSCOPY (3.43 ANGSTROMS) IN COMPLEX WITH MLST8; MTOR; RPTOR AND RHEBPHOSPHORYLATION AT THR-37 AND THR-46INTERACTION WITH RTORMUTAGENESIS OF GLN-113Atlas of Genetics and Cytogenetics in Oncology and Haematology2.25B=51-642.20E/F/G/H=54-662.10B=47-661.70B=51-672.40B=51-672.30B/F=51-642.30B/F=51-642.10B/F=51-642.10C=51-671.80C=51-672.90C=51-672.05C=51-672.10C/D=47-661.75B=50-832.10B/D=43-843.61B/D=51-641.90B/D=50-833.00T=99-1183.43X/Z=1-1183.00X/Z=1-11887283 sites, 1 O-linked glycan (3 sites)2330 antibodies from 48 providershumanEIF4EBP1Tissue enhanced (pancreas, salivary gland)geneEukaryotamTORC1-mediated signallingActivation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S33 hits in 1153 CRISPR screenshumanTbioProteinExpressed in body of pancreas and 176 other cell types or tissuesEIF4EBPEUKARYOTIC TRANSLATION INITIATION FACTOR 4E-BINDING PROTEINEUKARYOTIC TRANSLATION INITIATION FACTOR 4E-BINDING PROTEIN 1eIF_4EBPHSEukaryotic translation initiation factor 4E-binding protein 14E-BP1eIF4E-binding protein 1Phosphorylated heat- and acid-stable protein regulated by insulin 1PHAS-IEIF4EBP1Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.Hypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:12150926, PubMed:16271312, PubMed:17368478, PubMed:17631896, PubMed:22578813, PubMed:7935836, PubMed:8521827, PubMed:25702871). Interacts (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1 (PubMed:12747827, PubMed:24403073, PubMed:29236692).Localization to the nucleus is unaffected by phosphorylation status.The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF (PubMed:12588975, PubMed:12747827, PubMed:22578813, PubMed:7935836, PubMed:9465032, PubMed:24403073, PubMed:29236692). Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E (PubMed:12588975, PubMed:12747827, PubMed:22578813, PubMed:7935836, PubMed:9465032, PubMed:24403073, PubMed:29236692).Ubiquitinated: when eIF4E levels are low, hypophosphorylated form is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation and serving as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.Belongs to the eIF4E-binding protein family.Removed1Eukaryotic translation initiation factor 4E-binding protein 1124492118Disordered20Disordered2548Disordered64YXXXXLphi motif5460TOS motif114Polar residues15Polar residues34Polar residues7997Basic and acidic residues98N-acetylserinePhosphothreonine; by MTOR37Phosphothreonine41Phosphoserine44Phosphothreonine; by MTOR46Phosphothreonine50PhosphotyrosinePhosphoserine; by DYRK2, MAPK1, MAPK3 and MTOR65Phosphothreonine; by MTOR70Phosphothreonine77Phosphoserine83Phosphoserine96Phosphoserine; by DYRK2101Phosphoserine112Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)57Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-46; A-65 and A-70.AAbolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-37; A-65 and A-70.AImpaired ubiquitination by the BCR(KLHL25) complex.RAbolishes eIF4E-binding. Increased ubiquitination by the BCR(KLHL25) complex.AA59Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-37; A-46 and A-70.ADoes not affect ubiquitination by the BCR(KLHL25) complex.R69Abolishes phosphorylation by MTOR and increased ubiquitination by the BCR(KLHL25) complex; when associated with A-37; A-46 and A-65.ADoes not affect ubiquitination by the BCR(KLHL25) complex.R105Reduced interaction with RPTOR.A1135661626682false2false3false28false3false3false6false3false3false2false3false3false3false3false5false3false3true2AGO2DDIT4LEIF4EEIF4EEIF4E1BEIF4E2LMO2MEOX1MTORPICK1POU6F2RELRELRPTORTCF4ZNF655Mtor2007-01-233125802dbb4e8f68d8333a8baef21d58acf6f9MSGGSSCSQTPSRAIPATRRVVLGDGVQLPPGDYSTTPGGTLFSTTPGGTRIIYDRKFLMECRNSPVTKTPPRDLPTIPGVTSPSSDEPPMEASQSHLRNSPEDKRAGGEESQFEMDItruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue