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UniProtKB/Swiss-Prot entry Q13541


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name 4EBP1_HUMAN
Primary accession number Q13541
Secondary accession number Q6IBN3
Integrated into Swiss-Prot on September 19, 2003
Sequence was last modified on January 23, 2007 (Sequence version 3)
Annotations were last modified on    June 16, 2009 (Entry version 84)
Name and origin of the protein
Protein name Eukaryotic translation initiation factor 4E-binding protein 1
Synonyms eIF4E-binding protein 1
4E-BP1
Phosphorylated heat- and acid-stable protein regulated by insulin 1
PHAS-I
Gene name
Name: EIF4EBP1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH EIF4E, AND PHOSPHORYLATION.
TISSUE=Placenta;
DOI=10.1038/371762a0; PubMed=7935836 [NCBI, ExPASy, EBI, Israel, Japan]
Pause A., Belsham G.J., Gingras A.-C., Donze O., Lin T.-A., Lawrence J.C. Jr., Sonenberg N.;
"Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function.";
Nature 371:762-767(1994).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
Ito M., Shichijo S., Tsuda N., Ochi M., Harashima N., Saito N., Itoh K.;
"Identification of multiple genes and immunogenic epitopes of pancreatic cancer cells.";
Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).";
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Colon, and Lung;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
PROTEIN SEQUENCE OF 2-13, AND ACETYLATION AT SER-2.
TISSUE=Platelet;
DOI=10.1038/nbt810; PubMed=12665801 [NCBI, ExPASy, EBI, Israel, Japan]
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.;
"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.";
Nat. Biotechnol. 21:566-569(2003).
[7]
INTERACTION WITH EIF4E AND EIF4G.
PubMed=8521827 [NCBI, ExPASy, EBI, Israel, Japan]
Haghighat A., Mader S., Pause A., Sonenberg N.;
"Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E.";
EMBO J. 14:5701-5709(1995).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-46, AND MASS SPECTROMETRY.
DOI=10.1002/elps.200600782; PubMed=17487921 [NCBI, ExPASy, EBI, Israel, Japan]
Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line.";
Electrophoresis 28:2027-2034(2007).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; THR-70; SER-94 AND SER-101, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0611217104; PubMed=17287340 [NCBI, ExPASy, EBI, Israel, Japan]
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.;
"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry.";
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112, AND MASS SPECTROMETRY.
DOI=10.1126/science.1140321; PubMed=17525332 [NCBI, ExPASy, EBI, Israel, Japan]
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.";
Science 316:1160-1166(2007).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65 AND THR-68, AND MASS SPECTROMETRY.
DOI=10.2116/analsci.24.161; PubMed=18187866 [NCBI, ExPASy, EBI, Israel, Japan]
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.;
"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column.";
Anal. Sci. 24:161-166(2008).
[13]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35; THR-36; THR-37; THR-41; THR-46; THR-50; THR-70; THR-82; SER-83; SER-94 AND SER-101, AND MASS SPECTROMETRY.
DOI=10.1021/pr0705441; PubMed=18220336 [NCBI, ExPASy, EBI, Israel, Japan]
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.";
J. Proteome Res. 7:1346-1351(2008).
[14]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37; THR-41; THR-46; THR-50; TYR-54; SER-65; THR-70; THR-77; SER-83 AND SER-94, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan]
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[15]
IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J., Superti-Furga G., Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
[16]
STRUCTURE BY NMR OF 4-118.
PubMed=9684899 [NCBI, ExPASy, EBI, Israel, Japan]
Fletcher C.M., Wagner G.;
"The interaction of eIF4E with 4E-BP1 is an induced fit to a completely disordered protein.";
Protein Sci. 7:1639-1642(1998).
[17]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 36-70 IN COMPLEX WITH EIF4E AND MRNA CAP ANALOG.
DOI=10.1016/j.bbapap.2005.07.023; PubMed=16271312 [NCBI, ExPASy, EBI, Israel, Japan]
Tomoo K., Matsushita Y., Fujisaki H., Abiko F., Shen X., Taniguchi T., Miyagawa H., Kitamura K., Miura K., Ishida T.;
"Structural 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.";
Biochim. Biophys. Acta 1753:191-208(2005).
[18]
X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 51-67 IN COMPLEX WITH EIF4E2 AND MRNA CAP ANALOG.
DOI=10.1016/j.jmb.2007.02.019; PubMed=17368478 [NCBI, ExPASy, EBI, Israel, Japan]
Rosettani P., Knapp S., Vismara M.G., Rusconi L., Cameron A.D.;
"Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP-bound and unliganded forms.";
J. Mol. Biol. 368:691-705(2007).
[19]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 51-64 IN COMPLEX WITH EIF4E AND MRNA CAP ANALOG.
DOI=10.1016/j.jmb.2007.06.033; PubMed=17631896 [NCBI, ExPASy, EBI, Israel, Japan]
Brown C.J., McNae I., Fischer P.M., Walkinshaw M.D.;
"Crystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives.";
J. Mol. Biol. 372:7-15(2007).
Comments
  • FUNCTION: Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase pathway.
  • SUBUNIT: Nonphosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Rapamycin can attenuate insulin stimulation, mediated by FKBPs.
  • INTERACTION:
    P06730:EIF4E; NbExp=4; IntAct=EBI-74090, EBI-73440;
    O60573:EIF4E2; NbExp=1; IntAct=EBI-74090, EBI-398610;
    Q80ZJ3:Eif4e2 (xeno); NbExp=1; IntAct=EBI-74090, EBI-934970;
    Q9BSL1:UBAC1; NbExp=1; IntAct=EBI-74090, EBI-749370;
  • PTM: Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylated upon DNA damage, probably by ATM or ATR.
  • SIMILARITY: Belongs to the eIF4E-binding protein family.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
L36055; AAA62269.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB044548; BAB18650.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT007162; AAP35826.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
CR456769; CAG33050.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC004459; AAH04459.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC058073; AAH58073.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00002569; -.
PIR S50866; S50866.
RefSeq NP_004086.1; -.
UniGene Hs.411641
3D structure databases
PDB
1WKW; X-ray; 2.10 A; B=47-66.[ExPASy / RCSB / EBI]
2JGB; X-ray; 1.70 A; B=51-67.[ExPASy / RCSB / EBI]
2JGC; X-ray; 2.40 A; B=51-67.[ExPASy / RCSB / EBI]
2V8W; X-ray; 2.30 A; B/F=51-64.[ExPASy / RCSB / EBI]
2V8X; X-ray; 2.30 A; B/F=51-64.[ExPASy / RCSB / EBI]
2V8Y; X-ray; 2.10 A; B/F=51-64.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1WKW; -.
2JGB; -.
2JGC; -.
2V8W; -.
2V8X; -.
2V8Y; -.
DisProt DP00028; -.
ModBase Q13541.
Protein-protein interaction databases
IntAct Q13541; 10.
PTM databases
PhosphoSite Q13541; -.
Enzyme and pathway databases
Pathway_Interaction_DB insulin_pathway; Insulin Pathway.
mtor_4pathway; mTOR signaling pathway.
p38alphabetadownstreampathway; Signaling mediated by p38-alpha and p38-beta.
Reactome REACT_498; Signaling by Insulin receptor.
REACT_71; Gene Expression.
Organism-specific databases
GeneCards GC08P038007; -.
H-InvDB HIX0004694; -.
HGNC HGNC:3288; EIF4EBP1.
GenAtlas EIF4EBP1.
HPA CAB005032; -.
CAB005039; -.
MIM 602223; gene. [NCBI / EBI]
PharmGKB PA27715; -.
Gene expression databases
ArrayExpress Q13541; -.
Bgee Q13541; -.
CleanEx HS_EIF4EBP1; -.
GermOnline ENSG00000187840; Homo sapiens.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
QuickGo view.
Family and domain databases
InterPro IPR008606; EIF4EBP.
Graphical view of domain structure.
PANTHER PTHR12669; EIF4EBP; 1.
Pfam PF05456; eIF_4EBP; 1.
Pfam graphical view of domain structure.
Proteomic databases
PeptideAtlas Q13541; -.
PRIDE Q13541; -.
Genome annotation databases
Ensembl ENSG00000187840; Homo sapiens. [Contig view]
GeneID 1978; -.
KEGG hsa:1978; -.
Phylogenomic databases
HOGENOM Q13541; -.
HOVERGEN Q13541; -.
OMA Q13541; DKPAGGE.
Other
NextBio 8003; -.
PMAP-CutDB Q13541; -.
SOURCE EIF4EBP1; Homo sapiens.
ProtoNet Q13541.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Acetylation; Direct protein sequencing; Phosphoprotein; Protein synthesis inhibitor; Translation regulation.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
INIT_MET   1     1        Removed. 
CHAIN   2   118  117     Eukaryotic translation initiation factor 4E-binding protein 1. PRO_0000190513
MOD_RES   2     2        N-acetylserine. 
MOD_RES   35    35        Phosphoserine. 
MOD_RES   36    36        Phosphothreonine. 
MOD_RES   37    37        Phosphothreonine. 
MOD_RES   41    41        Phosphothreonine. 
MOD_RES   46    46        Phosphothreonine. 
MOD_RES   50    50        Phosphothreonine. 
MOD_RES   54    54        Phosphotyrosine. 
MOD_RES   65    65        Phosphoserine; by MAPK1 and MAPK3. 
MOD_RES   68    68        Phosphothreonine. 
MOD_RES   70    70        Phosphothreonine. 
MOD_RES   77    77        Phosphothreonine. 
MOD_RES   82    82        Phosphothreonine. 
MOD_RES   83    83        Phosphoserine. 
MOD_RES   94    94        Phosphoserine. 
MOD_RES   101   101        Phosphoserine. 
MOD_RES   112   112        Phosphoserine. 
HELIX   56    61  6      
Sequence information
Length: 118 AA [This is the length of the unprocessed precursor] Molecular weight: 12580 Da [This is the MW of the unprocessed precursor] CRC64: 1682A6BA74132966 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MSGGSSCSQT PSRAIPATRR VVLGDGVQLP PGDYSTTPGG TLFSTTPGGT RIIYDRKFLM 

        70         80         90        100        110 
ECRNSPVTKT PPRDLPTIPG VTSPSSDEPP MEASQSHLRN SPEDKRAGGE ESQFEMDI 

Q13541 in FASTA format

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