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EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)

Written2009-02Michael Clemens, Mark Coldwell
Dept of Chemistry, Biochemistry, School of Life Sciences, University of Sussex, Division of Basic Medical Sciences, St George's, University of London, United Kingdom (MCl); School of Biological Sciences, University of Southampton, United Kingdom (MCo)
Updated2012-03Michael Clemens, Mark Coldwell, Androulla Elia
School of Biological Sciences, University of Sussex, United Kingdom (MCl); Centre for Biological Sciences, University of Southampton, United Kingdom (MCo); Division of Biomedical Sciences, St George's, University of London, United Kingdom (AE)

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)PHAS-I
4E-BP1
Other aliasBP-1
4EBP1
MGC4316
HGNC (Hugo) EIF4EBP1
LocusID (NCBI) 1978
Atlas_Id 40432
Location 8p11.23  [Link to chromosome band 8p11]
Location_base_pair Starts at 38030502 and ends at 38060365 bp from pter ( according to hg19-Feb_2009)  [Mapping EIF4EBP1.png]
Fusion genes
(updated 2016)
ASPH (8q12.3) / EIF4EBP1 (8p11.23)EIF4EBP1 (8p11.23) / CDKN2A-AS1 (9p21.3)EIF4EBP1 (8p11.23) / PRKAA1 (5p13.1)
UNC5D (8p12) / EIF4EBP1 (8p11.23)

DNA/RNA

Description The EIF4EBP1 gene codes for 4E-BP1, one member of a family of small proteins that act as repressors of translation. The gene is 29,86 kb in length and contains three exons, comprising nucleotides 1-217, 218-397 and 398-859 of the mature mRNA.
Transcription EIF4EBP1 transcription is positively regulated by ATF4 in response to cell stress (Yamaguchi et al., 2008) and by Smad4 in response to transforming growth factor β (Azar et al., 2009). There is evidence that activity of the phosphatidylinositol 3-kinase (PI3K) and MAP kinase pathways can negatively regulate the transcription of EIF4EBP1 (Azar et al., 2008), possibly via the transcription factor Egr-1 (Rolli-Derkinderen et al., 2003).
Pseudogene Two pseudogenes with homology to 4E-BP1 exist in the human genome, located at 14q11.2 (LOC768328) and 22q12 (EIF4EBP1P), with the latter pseudogene present on the antisense strand of the gene locus encoding chromodomain helicase DNA binding protein 8 (CHD8).

Protein

 
  The diagram illustrates key regulatory features of the human 4E-BP1 protein, including the RAIP and TOS motifs that are important for the phosphorylation of the protein at Thr37, Thr46, Ser65, Thr70 and Ser101 by the Raptor/mTOR complex (Eguchi et al., 2006; Lee et al., 2008). Additional phosphorylation sites have been identified at Ser83 and Ser112. The region required for binding of 4E-BP1 to initiation factor eIF4E and a site of cleavage of the protein by caspases in apoptotic cells are also shown (diagram adapted from an original prepared by Dr C. Constantinou).
Description Human 4E-BP1 is a 118 amino acid protein (119 amino acids including the initiating methionine) and is encoded by an mRNA containing 877 nucleotides (including a short poly(A) tail). The mRNA has a 72 nucleotide 5' untranslated region and a 448 nucleotide 3' untranslated region. The coding region comprises nucleotides 73-429. The protein can be reversibly phosphorylated at Thr37, Thr46, Ser65, Thr70, Ser83, Ser101 and Ser112 in response to a variety of physiological stimuli. The key enzyme involved in these phosphorylations is the protein kinase mTOR, but other kinases may also be involved (Yonezawa et al., 2004).
Expression 4E-BP1 is ubiquitously expressed, although its presence is not essential to the viability of cells or the organism as a whole (Le Bacquer et al., 2007). The protein is stable (half-life more than 16h) but can be ubiquitinated and targeted for degradation by a mechanism that responds to its state of phosphorylation (Elia et al., 2008). The level of expression and state of phosphorylation of the protein may influence cellular phenotype, with high levels of phosphorylated 4E-BP1 in breast, ovary, and prostate tumours being associated with malignant progression and an adverse prognosis (Armengol et al., 2007). Conversely, hypophosphorylated 4E-BP1 may have an anti-oncogenic role due to its inhibitory effect on eIF4E and its potential pro-apoptotic properties (Li et al., 2002).
Localisation 4E-BP1 is present in both cytoplasm and nucleus. The hypophosphorylated protein in the latter compartment can sequester eIF4E within the nucleus under conditions of physiological stress (Rong et al., 2008).
Function The members of the 4E-BP family of proteins act by binding to the mRNA cap-binding protein eukaryotic initiation factor 4E (eIF4E), in competition with another initiation factor, eIF4G, that is essential for polypeptide chain initiation. Thus the availability of eIF4E for translation of cap-dependent mRNAs is limited by the extent to which this factor is sequestered by the 4E-BPs.
4E-BP1 is reversibly phosphorylated at multiple sites (see diagram above), in response to several physiological signals that promote translation (Proud, 2004; Wang et al., 2005; Proud, 2006). Such phosphorylations lower the affinity of 4E-BP1 for eIF4E and result in the dissociation of the two proteins, thereby enhancing the level of active eIF4E and promoting the translation of capped mRNAs, most likely in a selective manner (Averous et al., 2008). Conversely, physiological stresses and other conditions that inhibit translation - e.g. exposure of cells to cytokines of the TNFalpha family (Lang et al., 2007; Jeffrey et al., 2006) or activation of the tumour suppressor protein p53 (Tilleray et al., 2006; Constantinou and Clemens, 2007) - cause dephosphorylation of 4E-BP1 and increase binding of the latter to eIF4E. 4E-BP1 is also susceptible to other post-translational modifications, notably specific proteolytic cleavages (Tee and Proud, 2002; Constantinou et al., 2008) and phosphorylation-dependent ubiquitination (Elia et al., 2008).
There is good evidence for involvement of 4E-BP1 in malignant transformation. The protein can negatively regulate cell growth, block cell cycle progression and revert the transformed phenotype of cells over-expressing eIF4E (Rousseau et al., 1996; Jiang et al., 2003; Barnhart et al., 2008). It has been shown that 4E-BP1 is a key regulator of the oncogenic Akt (protein kinase B) and ERK (extracellular-regulated kinase) signalling pathways and it integrates the function of these pathways in tumours (She et al., 2010). Consistent with this, high levels of phosphorylated (inactive) 4E-BP1 indicate poor prognosis in some cancer patients (Castellvi et al., 2006; Frederick et al., 2011).
Although 4E-BP1 is not essential to viability the protein (together with its homologue 4E-BP2) is important for regulation of adipogenesis and insulin resistance (Le Bacquer et al., 2007). The 4E-BPs have also been reported to play a role in myelopoiesis (Olson et al., 2009). There is a major role for 4E-BP1 in the responses of cells to hypoxia, which promotes dephosphorylation of the protein (Koritzinsky et al., 2006; Connolly et al., 2006 ; Barnhart et al., 2008). It is likely that this response implements hypoxia-induced changes in gene expression at the translational level (Magagnin et al., 2008; Barnhart et al., 2008).
Homology 4E-BP1 was identified alongside another member of the eIF4E-binding protein family designated 4E-BP2 (Pause et al., 1994). A further homologue has also been identified, 4E-BP3 (Poulin et al., 1998), and these proteins respectively share 55,7% identity (82,0% similarity) and 50,8% identity (66,9% similarity) with 4E-BP1. All share the central eIF4E binding motif and are capable of competing with the eIF4G proteins for binding to eIF4E.
 

Mutations

Note No mutations have been identified.

Implicated in

Note
  
Entity Breast cancer
Prognosis Elevated expression of eIF4E in human cancer often correlates with poor prognosis (Culjkovic et al., 2007). Likewise, expression of phosphorylated 4E-BP1 (which is inactive as an inhibitor of eIF4E) is associated with malignant progression and an adverse prognosis in breast, ovary, and prostate tumours (Armengol et al., 2007).
Oncogenesis Because 4E-BP1 is an antagonist of the oncogenic initiation factor eIF4E (Avdulov et al., 2004), it might be anticipated that 4E-BP1 could function as a pro-apoptotic tumour suppressor protein. However it has been reported that a majority of large advanced breast cancers overexpress 4E-BP1 (Braunstein et al., 2007). The latter may contribute to tumourigenesis (in combination with overexpressed eIF4G) by promoting a hypoxia-activated switch in selective mRNA translation that enhances angiogenesis and tumour cell growth and survival.
  

Breakpoints

Note Although no breakpoints within the 4E-BP1 gene locus have been identified, the chromosomal region containing 4E-BP1 (8p11-12) is frequently rearranged in breast carcinomas. However, microarray profiling of the genes within these regions in breast tumours and cell lines shows that rearrangements of the chromosome do not correlate with significantly changed 4E-BP1 mRNA expression (Gelsi-Boyer et al., 2005).

Bibliography

4E-binding protein 1: a key molecular "funnel factor" in human cancer with clinical implications.
Armengol G, Rojo F, Castellvi J, Iglesias C, Cuatrecasas M, Pons B, Baselga J, Ramon y Cajal S.
Cancer Res. 2007 Aug 15;67(16):7551-5. (REVIEW)
PMID 17699757
 
Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells.
Avdulov S, Li S, Michalek V, Burrichter D, Peterson M, Perlman DM, Manivel JC, Sonenberg N, Yee D, Bitterman PB, Polunovsky VA.
Cancer Cell. 2004 Jun;5(6):553-63.
PMID 15193258
 
Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1.
Averous J, Fonseca BD, Proud CG.
Oncogene. 2008 Feb 14;27(8):1106-13. Epub 2007 Aug 27.
PMID 17724476
 
4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferation.
Azar R, Alard A, Susini C, Bousquet C, Pyronnet S.
EMBO J. 2009 Nov 18;28(22):3514-22. Epub 2009 Oct 15.
PMID 19834456
 
Phosphatidylinositol 3-kinase-dependent transcriptional silencing of the translational repressor 4E-BP1.
Azar R, Najib S, Lahlou H, Susini C, Pyronnet S.
Cell Mol Life Sci. 2008 Oct;65(19):3110-7.
PMID 18810319
 
Effects of 4E-BP1 expression on hypoxic cell cycle inhibition and tumor cell proliferation and survival.
Barnhart BC, Lam JC, Young RM, Houghton PJ, Keith B, Simon MC.
Cancer Biol Ther. 2008 Sep;7(9):1441-9. Epub 2008 Sep 11.
PMID 18708753
 
A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer.
Braunstein S, Karpisheva K, Pola C, Goldberg J, Hochman T, Yee H, Cangiarella J, Arju R, Formenti SC, Schneider RJ.
Mol Cell. 2007 Nov 9;28(3):501-12.
PMID 17996713
 
Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer.
Castellvi J, Garcia A, Rojo F, Ruiz-Marcellan C, Gil A, Baselga J, Ramon y Cajal S.
Cancer. 2006 Oct 15;107(8):1801-11.
PMID 16983702
 
Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells.
Connolly E, Braunstein S, Formenti S, Schneider RJ.
Mol Cell Biol. 2006 May;26(10):3955-65.
PMID 16648488
 
Activation of p53 stimulates proteasome-dependent truncation of eIF4E-binding protein 1 (4E-BP1).
Constantinou C, Elia A, Clemens MJ.
Biol Cell. 2008 May;100(5):279-89.
PMID 18021075
 
Controlling gene expression through RNA regulons: the role of the eukaryotic translation initiation factor eIF4E.
Culjkovic B, Topisirovic I, Borden KL.
Cell Cycle. 2007 Jan 1;6(1):65-9. Epub 2007 Jan 11. (REVIEW)
PMID 17245113
 
Different roles for the TOS and RAIP motifs of the translational regulator protein 4E-BP1 in the association with raptor and phosphorylation by mTOR in the regulation of cell size.
Eguchi S, Tokunaga C, Hidayat S, Oshiro N, Yoshino K, Kikkawa U, Yonezawa K.
Genes Cells. 2006 Jul;11(7):757-66.
PMID 16824195
 
Effects of protein phosphorylation on ubiquitination and stability of the translational inhibitor protein 4E-BP1.
Elia A, Constantinou C, Clemens MJ.
Oncogene. 2008 Jan 31;27(6):811-22. Epub 2007 Jul 23.
PMID 17653084
 
Phosphoproteomic analysis of signaling pathways in head and neck squamous cell carcinoma patient samples.
Frederick MJ, VanMeter AJ, Gadhikar MA, Henderson YC, Yao H, Pickering CC, Williams MD, El-Naggar AK, Sandulache V, Tarco E, Myers JN, Clayman GL, Liotta LA, Petricoin EF 3rd, Calvert VS, Fodale V, Wang J, Weber RS.
Am J Pathol. 2011 Feb;178(2):548-71.
PMID 21281788
 
Comprehensive profiling of 8p11-12 amplification in breast cancer.
Gelsi-Boyer V, Orsetti B, Cervera N, Finetti P, Sircoulomb F, Rouge C, Lasorsa L, Letessier A, Ginestier C, Monville F, Esteyries S, Adelaide J, Esterni B, Henry C, Ethier SP, Bibeau F, Mozziconacci MJ, Charafe-Jauffret E, Jacquemier J, Bertucci F, Birnbaum D, Theillet C, Chaffanet M.
Mol Cancer Res. 2005 Dec;3(12):655-67.
PMID 16380503
 
Interferon-alpha induces sensitization of cells to inhibition of protein synthesis by tumour necrosis factor-related apoptosis-inducing ligand.
Jeffrey IW, Elia A, Bornes S, Tilleray VJ, Gengatharan K, Clemens MJ.
FEBS J. 2006 Aug;273(16):3698-708.
PMID 16911520
 
Expression of constitutively active 4EBP-1 enhances p27Kip1 expression and inhibits proliferation of MCF7 breast cancer cells.
Jiang H, Coleman J, Miskimins R, Miskimins WK.
Cancer Cell Int. 2003 Feb 18;3(1):2.
PMID 12633504
 
Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control.
Koritzinsky M, Magagnin MG, van den Beucken T, Seigneuric R, Savelkouls K, Dostie J, Pyronnet S, Kaufman RJ, Weppler SA, Voncken JW, Lambin P, Koumenis C, Sonenberg N, Wouters BG.
EMBO J. 2006 Mar 8;25(5):1114-25. Epub 2006 Feb 9.
PMID 16467844
 
Regulation of muscle protein synthesis during sepsis and inflammation.
Lang CH, Frost RA, Vary TC.
Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E453-9. Epub 2007 May 15. (REVIEW)
PMID 17505052
 
Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2.
Le Bacquer O, Petroulakis E, Paglialunga S, Poulin F, Richard D, Cianflone K, Sonenberg N.
J Clin Invest. 2007 Feb;117(2):387-96.
PMID 17273556
 
Analysis of the regulatory motifs in eukaryotic initiation factor 4E-binding protein 1.
Lee VH, Healy T, Fonseca BD, Hayashi A, Proud CG.
FEBS J. 2008 May;275(9):2185-99. Epub 2008 Apr 1.
PMID 18384376
 
Translational control of cell fate: availability of phosphorylation sites on translational repressor 4E-BP1 governs its proapoptotic potency.
Li S, Sonenberg N, Gingras AC, Peterson M, Avdulov S, Polunovsky VA, Bitterman PB.
Mol Cell Biol. 2002 Apr;22(8):2853-61.
PMID 11909977
 
The mTOR target 4E-BP1 contributes to differential protein expression during normoxia and hypoxia through changes in mRNA translation efficiency.
Magagnin MG, van den Beucken T, Sergeant K, Lambin P, Koritzinsky M, Devreese B, Wouters BG.
Proteomics. 2008 Mar;8(5):1019-28.
PMID 18219697
 
Impaired myelopoiesis in mice lacking the repressors of translation initiation, 4E-BP1 and 4E-BP2.
Olson KE, Booth GC, Poulin F, Sonenberg N, Beretta L.
Immunology. 2009 Sep;128(1 Suppl):e376-84. Epub 2008 Oct 31.
PMID 19175792
 
Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function.
Pause A, Belsham GJ, Gingras AC, Donze O, Lin TA, Lawrence JC Jr, Sonenberg N.
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PMID 7935836
 
4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein family.
Poulin F, Gingras AC, Olsen H, Chevalier S, Sonenberg N.
J Biol Chem. 1998 May 29;273(22):14002-7.
PMID 9593750
 
Regulation of protein synthesis by insulin.
Proud CG.
Biochem Soc Trans. 2006 Apr;34(Pt 2):213-6. (REVIEW)
PMID 16545079
 
ERK and p38 inhibit the expression of 4E-BP1 repressor of translation through induction of Egr-1.
Rolli-Derkinderen M, Machavoine F, Baraban JM, Grolleau A, Beretta L, Dy M.
J Biol Chem. 2003 May 23;278(21):18859-67. Epub 2003 Mar 4.
PMID 12618431
 
Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs.
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PMID 18515545
 
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PMID 8957083
 
4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors.
She QB, Halilovic E, Ye Q, Zhen W, Shirasawa S, Sasazuki T, Solit DB, Rosen N.
Cancer Cell. 2010 Jul 13;18(1):39-51.
PMID 20609351
 
Caspase cleavage of initiation factor 4E-binding protein 1 yields a dominant inhibitor of cap-dependent translation and reveals a novel regulatory motif.
Tee AR, Proud CG.
Mol Cell Biol. 2002 Mar;22(6):1674-83.
PMID 11865047
 
Regulation of protein synthesis by inducible wild-type p53 in human lung carcinoma cells.
Tilleray V, Constantinou C, Clemens MJ.
FEBS Lett. 2006 Mar 20;580(7):1766-70. Epub 2006 Feb 21.
PMID 16504179
 
Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins.
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Mol Cell Biol. 2005 Apr;25(7):2558-72.
PMID 15767663
 
ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress.
Yamaguchi S, Ishihara H, Yamada T, Tamura A, Usui M, Tominaga R, Munakata Y, Satake C, Katagiri H, Tashiro F, Aburatani H, Tsukiyama-Kohara K, Miyazaki J, Sonenberg N, Oka Y.
Cell Metab. 2008 Mar;7(3):269-76.
PMID 18316032
 
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Curr Top Microbiol Immunol. 2004;279:271-82. (REVIEW)
PMID 14560963
 

Citation

This paper should be referenced as such :
Clemens, M ; Coldwell, M ; Elia, A
EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(8):540-544.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/EIF4EBP1ID40432ch8p12.html
History of this paper:
Clemens, M ; Coldwell, M. EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1). Atlas Genet Cytogenet Oncol Haematol. 2010;14(1):11-14.
http://documents.irevues.inist.fr/bitstream/handle/2042/44655/02-2009-EIF4EBP1ID40432ch8p12.pdf


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 3 ]
  Lymphangioleiomyomatosis
Soft Tissues: Lymphangioleiomyoma
Lung: Translocations in Squamous Cell Carcinoma


External links

Nomenclature
HGNC (Hugo)EIF4EBP1   3288
Cards
AtlasEIF4EBP1ID40432ch8p12
Entrez_Gene (NCBI)EIF4EBP1  1978  eukaryotic translation initiation factor 4E binding protein 1
Aliases4E-BP1; 4EBP1; BP-1; PHAS-I
GeneCards (Weizmann)EIF4EBP1
Ensembl hg19 (Hinxton)ENSG00000187840 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000187840 [Gene_View]  chr8:38030502-38060365 [Contig_View]  EIF4EBP1 [Vega]
ICGC DataPortalENSG00000187840
TCGA cBioPortalEIF4EBP1
AceView (NCBI)EIF4EBP1
Genatlas (Paris)EIF4EBP1
WikiGenes1978
SOURCE (Princeton)EIF4EBP1
Genetics Home Reference (NIH)EIF4EBP1
Genomic and cartography
GoldenPath hg38 (UCSC)EIF4EBP1  -     chr8:38030502-38060365 +  8p11.23   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)EIF4EBP1  -     8p11.23   [Description]    (hg19-Feb_2009)
EnsemblEIF4EBP1 - 8p11.23 [CytoView hg19]  EIF4EBP1 - 8p11.23 [CytoView hg38]
Mapping of homologs : NCBIEIF4EBP1 [Mapview hg19]  EIF4EBP1 [Mapview hg38]
OMIM602223   
Gene and transcription
Genbank (Entrez)AB044548 AK312011 BC004459 BC058073 BF964628
RefSeq transcript (Entrez)NM_004095
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)EIF4EBP1
Cluster EST : UnigeneHs.411641 [ NCBI ]
CGAP (NCI)Hs.411641
Alternative Splicing GalleryENSG00000187840
Gene ExpressionEIF4EBP1 [ NCBI-GEO ]   EIF4EBP1 [ EBI - ARRAY_EXPRESS ]   EIF4EBP1 [ SEEK ]   EIF4EBP1 [ MEM ]
Gene Expression Viewer (FireBrowse)EIF4EBP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1978
GTEX Portal (Tissue expression)EIF4EBP1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13541   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13541  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13541
Splice isoforms : SwissVarQ13541
PhosPhoSitePlusQ13541
Domains : Interpro (EBI)EIF4EBP   
Domain families : Pfam (Sanger)eIF_4EBP (PF05456)   
Domain families : Pfam (NCBI)pfam05456   
Conserved Domain (NCBI)EIF4EBP1
DMDM Disease mutations1978
Blocks (Seattle)EIF4EBP1
PDB (SRS)1EJ4    1WKW    2JGB    2JGC    2V8W    2V8X    2V8Y    3HXG    3HXI    3M93    3M94    3U7X    4UED    5BXV    5EKV   
PDB (PDBSum)1EJ4    1WKW    2JGB    2JGC    2V8W    2V8X    2V8Y    3HXG    3HXI    3M93    3M94    3U7X    4UED    5BXV    5EKV   
PDB (IMB)1EJ4    1WKW    2JGB    2JGC    2V8W    2V8X    2V8Y    3HXG    3HXI    3M93    3M94    3U7X    4UED    5BXV    5EKV   
PDB (RSDB)1EJ4    1WKW    2JGB    2JGC    2V8W    2V8X    2V8Y    3HXG    3HXI    3M93    3M94    3U7X    4UED    5BXV    5EKV   
Structural Biology KnowledgeBase1EJ4    1WKW    2JGB    2JGC    2V8W    2V8X    2V8Y    3HXG    3HXI    3M93    3M94    3U7X    4UED    5BXV    5EKV   
SCOP (Structural Classification of Proteins)1EJ4    1WKW    2JGB    2JGC    2V8W    2V8X    2V8Y    3HXG    3HXI    3M93    3M94    3U7X    4UED    5BXV    5EKV   
CATH (Classification of proteins structures)1EJ4    1WKW    2JGB    2JGC    2V8W    2V8X    2V8Y    3HXG    3HXI    3M93    3M94    3U7X    4UED    5BXV    5EKV   
SuperfamilyQ13541
Human Protein AtlasENSG00000187840
Peptide AtlasQ13541
HPRD03746
IPIIPI00002569   
Protein Interaction databases
DIP (DOE-UCLA)Q13541
IntAct (EBI)Q13541
FunCoupENSG00000187840
BioGRIDEIF4EBP1
STRING (EMBL)EIF4EBP1
ZODIACEIF4EBP1
Ontologies - Pathways
QuickGOQ13541
Ontology : AmiGOG1/S transition of mitotic cell cycle  IRES-dependent translational initiation  response to ischemia  protein binding  nucleus  cytosol  cytosol  eukaryotic initiation factor 4E binding  insulin receptor signaling pathway  lung development  translation repressor activity  negative regulation of protein complex assembly  TOR signaling  protein complex  response to ethanol  positive regulation of mitotic cell cycle  negative regulation of translational initiation  protein phosphatase 2A binding  cellular response to hypoxia  cellular response to dexamethasone stimulus  response to amino acid starvation  
Ontology : EGO-EBIG1/S transition of mitotic cell cycle  IRES-dependent translational initiation  response to ischemia  protein binding  nucleus  cytosol  cytosol  eukaryotic initiation factor 4E binding  insulin receptor signaling pathway  lung development  translation repressor activity  negative regulation of protein complex assembly  TOR signaling  protein complex  response to ethanol  positive regulation of mitotic cell cycle  negative regulation of translational initiation  protein phosphatase 2A binding  cellular response to hypoxia  cellular response to dexamethasone stimulus  response to amino acid starvation  
Pathways : BIOCARTARegulation of eIF4e and p70 S6 Kinase [Genes]    Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway [Genes]    mTOR Signaling Pathway [Genes]   
Pathways : KEGGRNA transport    ErbB signaling pathway    HIF-1 signaling pathway    mTOR signaling pathway    PI3K-Akt signaling pathway    Insulin signaling pathway    Acute myeloid leukemia   
REACTOMEQ13541 [protein]
REACTOME PathwaysR-HSA-72662 [pathway]   
NDEx NetworkEIF4EBP1
Atlas of Cancer Signalling NetworkEIF4EBP1
Wikipedia pathwaysEIF4EBP1
Orthology - Evolution
OrthoDB1978
GeneTree (enSembl)ENSG00000187840
Phylogenetic Trees/Animal Genes : TreeFamEIF4EBP1
HOVERGENQ13541
HOGENOMQ13541
Homologs : HomoloGeneEIF4EBP1
Homology/Alignments : Family Browser (UCSC)EIF4EBP1
Gene fusions - Rearrangements
Fusion : MitelmanEIF4EBP1/CDKN2A-AS1 [8p11.23/9p21.3]  
Fusion : MitelmanEIF4EBP1/PRKAA1 [8p11.23/5p13.1]  [t(5;8)(p13;p11)]  
Fusion : MitelmanUNC5D/EIF4EBP1 [8p12/8p11.23]  [t(8;8)(p11;p12)]  
Fusion: TCGAUNC5D 8p12 EIF4EBP1 8p11.23 PRAD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerEIF4EBP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)EIF4EBP1
dbVarEIF4EBP1
ClinVarEIF4EBP1
1000_GenomesEIF4EBP1 
Exome Variant ServerEIF4EBP1
ExAC (Exome Aggregation Consortium)EIF4EBP1 (select the gene name)
Genetic variants : HAPMAP1978
Genomic Variants (DGV)EIF4EBP1 [DGVbeta]
DECIPHEREIF4EBP1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisEIF4EBP1 
Mutations
ICGC Data PortalEIF4EBP1 
TCGA Data PortalEIF4EBP1 
Broad Tumor PortalEIF4EBP1
OASIS PortalEIF4EBP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICEIF4EBP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDEIF4EBP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch EIF4EBP1
DgiDB (Drug Gene Interaction Database)EIF4EBP1
DoCM (Curated mutations)EIF4EBP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)EIF4EBP1 (select a term)
intoGenEIF4EBP1
NCG5 (London)EIF4EBP1
Cancer3DEIF4EBP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602223   
Orphanet
MedgenEIF4EBP1
Genetic Testing Registry EIF4EBP1
NextProtQ13541 [Medical]
TSGene1978
GENETestsEIF4EBP1
Target ValidationEIF4EBP1
Huge Navigator EIF4EBP1 [HugePedia]
snp3D : Map Gene to Disease1978
BioCentury BCIQEIF4EBP1
ClinGenEIF4EBP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1978
Chemical/Pharm GKB GenePA27715
Clinical trialEIF4EBP1
Miscellaneous
canSAR (ICR)EIF4EBP1 (select the gene name)
Probes
Litterature
PubMed240 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineEIF4EBP1
EVEXEIF4EBP1
GoPubMedEIF4EBP1
iHOPEIF4EBP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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