4EBP1_MOUSE
ID 4EBP1_MOUSE Reviewed; 117 AA.
AC Q60876; Q3TDS8; Q9CZ40;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 160.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAH02045.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION,
RP AND INTERACTION WITH EIF4E.
RX PubMed=7629182; DOI=10.1074/jbc.270.31.18531;
RA Lin T.-A., Kong X., Saltiel A.R., Blackshear P.J., Lawrence J.C. Jr.;
RT "Control of PHAS-I by insulin in 3T3-L1 adipocytes. Synthesis, degradation,
RT and phosphorylation by a rapamycin-sensitive and mitogen-activated protein
RT kinase-independent pathway.";
RL J. Biol. Chem. 270:18531-18538(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000269|PubMed:15489334};
RC TISSUE=Mammary gland {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 [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=17273556; DOI=10.1172/jci29528;
RA Le Bacquer O., Petroulakis E., Paglialunga S., Poulin F., Richard D.,
RA Cianflone K., Sonenberg N.;
RT "Elevated sensitivity to diet-induced obesity and insulin resistance in
RT mice lacking 4E-BP1 and 4E-BP2.";
RL J. Clin. Invest. 117:387-396(2007).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=19175792; DOI=10.1111/j.1365-2567.2008.02981.x;
RA Olson K.E., Booth G.C., Poulin F., Sonenberg N., Beretta L.;
RT "Impaired myelopoiesis in mice lacking the repressors of translation
RT initiation, 4E-BP1 and 4E-BP2.";
RL Immunology 128:E376-E384(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-36; THR-40; SER-43; THR-45;
RP SER-64; THR-69; SER-95; SER-99 AND SER-100, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP INTERACTION WITH RPTOR, AND MUTAGENESIS OF PHE-113.
RX PubMed=24139800; DOI=10.1016/j.celrep.2013.09.017;
RA Hartman N.W., Lin T.V., Zhang L., Paquelet G.E., Feliciano D.M., Bordey A.;
RT "mTORC1 targets the translational repressor 4E-BP2, but not S6 kinase 1/2,
RT to regulate neural stem cell self-renewal in vivo.";
RL Cell Rep. 5:433-444(2013).
RN [9]
RP PHOSPHORYLATION AT THR-36 AND THR-45.
RX PubMed=26359501; DOI=10.1074/jbc.m115.678433;
RA Cattin M.E., Wang J., Weldrick J.J., Roeske C.L., Mak E., Thorn S.L.,
RA DaSilva J.N., Wang Y., Lusis A.J., Burgon P.G.;
RT "Deletion of MLIP (muscle-enriched A-type lamin-interacting protein) leads
RT to cardiac hyperactivation of Akt/mammalian target of rapamycin (mTOR) and
RT impaired cardiac adaptation.";
RL J. Biol. Chem. 290:26699-26714(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 (By similarity). Mediates the regulation of protein translation by
CC hormones, growth factors and other stimuli that signal through the MAP
CC kinase and mTORC1 pathways (PubMed:7629182).
CC {ECO:0000250|UniProtKB:Q13541, ECO:0000269|PubMed:7629182}.
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:7629182). Interacts (via TOS motif) with RPTOR; promoting
CC phosphorylation by mTORC1 (PubMed:24139800).
CC {ECO:0000269|PubMed:24139800, ECO:0000269|PubMed:7629182}.
CC -!- INTERACTION:
CC Q60876; P63073: Eif4e; NbExp=3; IntAct=EBI-398674, EBI-2000006;
CC -!- TISSUE SPECIFICITY: Highest expression in fat cells.
CC {ECO:0000269|PubMed:7629182}.
CC -!- DOMAIN: The TOS motif mediates interaction with RPTOR, leading to
CC promote phosphorylation by mTORC1 complex.
CC {ECO:0000269|PubMed:24139800}.
CC -!- PTM: Phosphorylated on serine and threonine residues in response to
CC insulin, EGF and PDGF. Phosphorylation at Thr-36, Thr-45, Ser-64 and
CC Thr-69, corresponding to the hyperphosphorylated form, is regulated by
CC mTORC1 and abolishes binding to EIF4E. {ECO:0000269|PubMed:7629182}.
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-36, Thr-45, Ser-64 and Thr-69) or
CC associated with eIF4E. {ECO:0000250|UniProtKB:Q13541}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking both Eif4ebp1 and Eif4ebp2 display
CC increased their sensitivity to diet-induced obesity (PubMed:17273556).
CC Mice lacking both Eif4ebp1 and Eif4ebp2 show defects in myelopoiesis:
CC mice display an increased number of immature granulocytic precursors,
CC associated with a decreased number of mature granulocytic elements
CC (PubMed:19175792). {ECO:0000269|PubMed:17273556,
CC ECO:0000269|PubMed:19175792}.
CC -!- SIMILARITY: Belongs to the eIF4E-binding protein family. {ECO:0000305}.
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DR EMBL; U28656; AAA88818.1; -; mRNA.
DR EMBL; AK013033; BAB28612.1; -; mRNA.
DR EMBL; AK169979; BAE41494.1; -; mRNA.
DR EMBL; AK170031; BAE41521.1; -; mRNA.
DR EMBL; BC002045; AAH02045.1; -; mRNA.
DR CCDS; CCDS22214.1; -.
DR PIR; A57396; A57396.
DR RefSeq; NP_031944.3; NM_007918.3.
DR AlphaFoldDB; Q60876; -.
DR SMR; Q60876; -.
DR BioGRID; 199421; 11.
DR DIP; DIP-32577N; -.
DR IntAct; Q60876; 4.
DR MINT; Q60876; -.
DR STRING; 10090.ENSMUSP00000033880; -.
DR iPTMnet; Q60876; -.
DR PhosphoSitePlus; Q60876; -.
DR EPD; Q60876; -.
DR jPOST; Q60876; -.
DR MaxQB; Q60876; -.
DR PaxDb; Q60876; -.
DR PeptideAtlas; Q60876; -.
DR PRIDE; Q60876; -.
DR ProteomicsDB; 285687; -.
DR Antibodypedia; 3558; 2081 antibodies from 48 providers.
DR DNASU; 13685; -.
DR Ensembl; ENSMUST00000033880; ENSMUSP00000033880; ENSMUSG00000031490.
DR GeneID; 13685; -.
DR KEGG; mmu:13685; -.
DR UCSC; uc009lih.1; mouse.
DR CTD; 1978; -.
DR MGI; MGI:103267; Eif4ebp1.
DR VEuPathDB; HostDB:ENSMUSG00000031490; -.
DR eggNOG; ENOG502S4SY; Eukaryota.
DR GeneTree; ENSGT00940000159932; -.
DR HOGENOM; CLU_111706_0_0_1; -.
DR InParanoid; Q60876; -.
DR OMA; QMPDVYS; -.
DR OrthoDB; 1597535at2759; -.
DR PhylomeDB; Q60876; -.
DR TreeFam; TF101530; -.
DR Reactome; R-MMU-166208; mTORC1-mediated signalling.
DR Reactome; R-MMU-72662; Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S.
DR BioGRID-ORCS; 13685; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Eif4ebp1; mouse.
DR PRO; PR:Q60876; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q60876; protein.
DR Bgee; ENSMUSG00000031490; Expressed in parotid gland and 216 other tissues.
DR Genevisible; Q60876; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:AgBase.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0099524; C:postsynaptic cytosol; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0008190; F:eukaryotic initiation factor 4E binding; IPI:MGI.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISO:MGI.
DR GO; GO:0031369; F:translation initiation factor binding; ISO:MGI.
DR GO; GO:0030371; F:translation repressor activity; ISS:UniProtKB.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IDA:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:MGI.
DR GO; GO:0002192; P:IRES-dependent translational initiation of linear mRNA; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0045947; P:negative regulation of translational initiation; IDA:MGI.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:MGI.
DR GO; GO:0006446; P:regulation of translational initiation; TAS:MGI.
DR GO; GO:1990928; P:response to amino acid starvation; ISO:MGI.
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; ISS:UniProtKB.
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 Acetylation; Isopeptide bond; Phosphoprotein; Protein synthesis inhibitor;
KW Reference proteome; Translation regulation; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT CHAIN 2..117
FT /note="Eukaryotic translation initiation factor 4E-binding
FT protein 1"
FT /id="PRO_0000190514"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 64..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 53..59
FT /note="YXXXXLphi motif"
FT /evidence="ECO:0000250|UniProtKB:P70445"
FT MOTIF 113..117
FT /note="TOS motif"
FT /evidence="ECO:0000269|PubMed:24139800"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 84..101
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 103..117
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 36
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:26359501,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 40
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 45
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:26359501,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 49
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 53
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 69
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT CROSSLNK 56
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MUTAGEN 113
FT /note="F->A: Impaired interaction with RPTOR."
FT /evidence="ECO:0000269|PubMed:24139800"
FT CONFLICT 93
FT /note="S -> N (in Ref. 2; BAB28612)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 117 AA; 12325 MW; 3458D5687468A7EA CRC64;
MSAGSSCSQT PSRAIPTRRV ALGDGVQLPP GDYSTTPGGT LFSTTPGGTR IIYDRKFLME
CRNSPVAKTP PKDLPAIPGV TSPTSDEPPM QASQSQLPSS PEDKRAGGEE SQFEMDI
