Human Gene EIF4EBP1 (uc003xks.3) Description and Page Index
  Description: Homo sapiens eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), mRNA.
RefSeq Summary (NM_004095): This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of mRNA translation. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: BE739835.1, AB044548.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000338825.5/ ENSP00000340691.4 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr8:37,888,020-37,917,883 Size: 29,864 Total Exon Count: 3 Strand: +
Coding Region
   Position: hg19 chr8:37,888,092-37,917,453 Size: 29,362 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr8:37,888,020-37,917,883)mRNA (may differ from genome)Protein (118 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Eukaryotic translation initiation factor 4E-binding protein 1; Short=4E-BP1; Short=eIF4E-binding protein 1; AltName: Full=Phosphorylated heat- and acid-stable protein regulated by insulin 1; Short=PHAS-I;
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 and mTORC1 pathways.
SUBUNIT: Nonphosphorylated 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. Interacts with RPTOR.
INTERACTION: P06730:EIF4E; NbExp=4; IntAct=EBI-74090, EBI-73440; P42345:MTOR; NbExp=2; IntAct=EBI-74090, EBI-359260; Q9JLN9:Mtor (xeno); NbExp=2; IntAct=EBI-74090, EBI-1571628; Q8N122:RPTOR; NbExp=4; IntAct=EBI-74090, EBI-1567928;
PTM: Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylation at Thr-37, Thr-46, Ser- 65 and Thr-70 is regulated by mTORC1. Phosphorylated upon DNA damage, probably by ATM or ATR.
SIMILARITY: Belongs to the eIF4E-binding protein family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): EIF4EBP1
CDC HuGE Published Literature: EIF4EBP1

-  MalaCards Disease Associations
  MalaCards Gene Search: EIF4EBP1
Diseases sorted by gene-association score: tuberous sclerosis (5), tracheal cancer (3), rhabdomyosarcoma (3), large intestine adenocarcinoma (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D019256 Cadmium Chloride
  • D020123 Sirolimus
  • C059514 resveratrol
  • D016572 Cyclosporine
  • C070379 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • C085911 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • C016583 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • C031143 AICA ribonucleotide
  • D000638 Amiodarone
  • D002110 Caffeine
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 86.74 RPKM in Pancreas
Total median expression: 914.09 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -25.4072-0.353 Picture PostScript Text
3' UTR -160.50430-0.373 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008606 - EIF4EBP

Pfam Domains:
PF05456 - Eukaryotic translation initiation factor 4E binding protein (EIF4EBP)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

- X-ray MuPIT

- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2V8W - X-ray MuPIT 2V8X - X-ray MuPIT 2V8Y - X-ray MuPIT
3HXG - X-ray 3HXI - X-ray 3M93 - X-ray
3M94 - X-ray 3U7X - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q13541
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 Protein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0008190 eukaryotic initiation factor 4E binding
GO:0030371 translation repressor activity

Biological Process:
GO:0000082 G1/S transition of mitotic cell cycle
GO:0002192 IRES-dependent translational initiation
GO:0006417 regulation of translation
GO:0008286 insulin receptor signaling pathway
GO:0017148 negative regulation of translation
GO:0031929 TOR signaling
GO:0045931 positive regulation of mitotic cell cycle
GO:0045947 negative regulation of translational initiation
GO:0071549 cellular response to dexamethasone stimulus

Cellular Component:
GO:0005829 cytosol

-  Descriptions from all associated GenBank mRNAs
  LF371869 - JP 2014500723-A/179372: Polycomb-Associated Non-Coding RNAs.
LF384355 - JP 2014500723-A/191858: Polycomb-Associated Non-Coding RNAs.
BC004459 - Homo sapiens eukaryotic translation initiation factor 4E binding protein 1, mRNA (cDNA clone MGC:4316 IMAGE:2820216), complete cds.
AB044548 - Homo sapiens P/OKcl.6 mRNA for eukaryotic translation initiation factor 4E binding protein 1, complete cds.
AK312011 - Homo sapiens cDNA, FLJ92286, Homo sapiens eukaryotic translation initiation factor 4E bindingprotein 1 (EIF4EBP1), mRNA.
BC058073 - Homo sapiens eukaryotic translation initiation factor 4E binding protein 1, mRNA (cDNA clone MGC:64871 IMAGE:5190933), complete cds.
JD329304 - Sequence 310328 from Patent EP1572962.
DQ893731 - Synthetic construct Homo sapiens clone IMAGE:100008191; FLH164028.01L; RZPDo839B12161D eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) gene, encodes complete protein.
DQ890570 - Synthetic construct clone IMAGE:100003200; FLH164032.01X; RZPDo839B12162D eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) gene, encodes complete protein.
AB590574 - Synthetic construct DNA, clone: pFN21AE1520, Homo sapiens EIF4EBP1 gene for eukaryotic translation initiation factor 4E binding protein 1, without stop codon, in Flexi system.
KJ891096 - Synthetic construct Homo sapiens clone ccsbBroadEn_00490 EIF4EBP1 gene, encodes complete protein.
BT007162 - Homo sapiens eukaryotic translation initiation factor 4E binding protein 1 mRNA, complete cds.
CR456769 - Homo sapiens full open reading frame cDNA clone RZPDo834D124D for gene EIF4EBP1, eukaryotic translation initiation factor 4E binding protein 1; complete cds, incl. stopcodon.
L36055 - Human 4E-binding protein 1 mRNA, complete cds.
LF371879 - JP 2014500723-A/179382: Polycomb-Associated Non-Coding RNAs.
LF371880 - JP 2014500723-A/179383: Polycomb-Associated Non-Coding RNAs.
JD076762 - Sequence 57786 from Patent EP1572962.
LF371882 - JP 2014500723-A/179385: Polycomb-Associated Non-Coding RNAs.
JD331539 - Sequence 312563 from Patent EP1572962.
JD181971 - Sequence 162995 from Patent EP1572962.
JD561505 - Sequence 542529 from Patent EP1572962.
JD516639 - Sequence 497663 from Patent EP1572962.
JD381530 - Sequence 362554 from Patent EP1572962.
JD381110 - Sequence 362134 from Patent EP1572962.
JD450819 - Sequence 431843 from Patent EP1572962.
LF371883 - JP 2014500723-A/179386: Polycomb-Associated Non-Coding RNAs.
JD182754 - Sequence 163778 from Patent EP1572962.
JD394069 - Sequence 375093 from Patent EP1572962.
LF371884 - JP 2014500723-A/179387: Polycomb-Associated Non-Coding RNAs.
MA607446 - JP 2018138019-A/179372: Polycomb-Associated Non-Coding RNAs.
MA619932 - JP 2018138019-A/191858: Polycomb-Associated Non-Coding RNAs.
MA607456 - JP 2018138019-A/179382: Polycomb-Associated Non-Coding RNAs.
MA607457 - JP 2018138019-A/179383: Polycomb-Associated Non-Coding RNAs.
MA607459 - JP 2018138019-A/179385: Polycomb-Associated Non-Coding RNAs.
MA607460 - JP 2018138019-A/179386: Polycomb-Associated Non-Coding RNAs.
MA607461 - JP 2018138019-A/179387: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04012 - ErbB signaling pathway
hsa04150 - mTOR signaling pathway
hsa04910 - Insulin signaling pathway
hsa05221 - Acute myeloid leukemia

BioCarta from NCI Cancer Genome Anatomy Project
h_eif4Pathway - Regulation of eIF4e and p70 S6 Kinase
h_igf1mtorpathway - Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway
h_mTORPathway - mTOR Signaling Pathway

Reactome (by CSHL, EBI, and GO)

Protein Q13541 (Reactome details) participates in the following event(s):

R-HSA-72622 Release of eIF4E from the inactive eIF4E:4E-BP complex
R-HSA-165708 Dissociation of phosphorylated 4EBP1 from eIF4E
R-HSA-165692 Phosphorylation of 4E-BP1 by activated mTORC1
R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
R-HSA-166208 mTORC1-mediated signalling
R-HSA-72737 Cap-dependent Translation Initiation
R-HSA-165159 mTOR signalling
R-HSA-72613 Eukaryotic Translation Initiation
R-HSA-162582 Signal Transduction
R-HSA-72766 Translation
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: 4EBP1_HUMAN, B2R502, D3DSW8, NM_004095, NP_004086, Q13541, Q6IBN3
UCSC ID: uc003xks.3
RefSeq Accession: NM_004095
Protein: Q13541 (aka 4EBP1_HUMAN or 4BP1_HUMAN)
CCDS: CCDS6100.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_004095.3
exon count: 3CDS single in 3' UTR: no RNA size: 877
ORF size: 357CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 882.00frame shift in genome: no % Coverage: 97.95
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.