EIF4EBP2 eukaryotic translation initiation factor 4E binding protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EIF4EBP2provided by HGNC
Official Full Name: eukaryotic translation initiation factor 4E binding protein 2provided by HGNC
Primary source: HGNC:HGNC:3289
See related: Ensembl:ENSG00000148730 MIM:602224; AllianceGenome:HGNC:3289
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: 4EBP2; PHASII
Summary: This gene encodes a member of the eukaryotic translation initiation factor 4E binding protein family. The gene products of this family bind eIF4E and inhibit translation initiation. However, insulin and other growth factors can release this inhibition via a phosphorylation-dependent disruption of their binding to eIF4E. Regulation of protein production through these gene products have been implicated in cell proliferation, cell differentiation and viral infection. [provided by RefSeq, Oct 2008]
Expression: Ubiquitous expression in fat (RPKM 50.2), kidney (RPKM 34.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q22.1

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (70404145..70428618)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (71273202..71298049)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (72163901..72188374)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The human eIF4E:4E-BP2 complex structure for studying hyperphosphorylation.
Title: The human eIF4E:4E-BP2 complex structure for studying hyperphosphorylation.
4EBP2-regulated protein translation has a critical role in high-fat diet-induced insulin resistance in hepatocytes.
Title: 4EBP2-regulated protein translation has a critical role in high-fat diet-induced insulin resistance in hepatocytes.
This study combines molecular dynamics simulations and discrete path sampling to construct energy landscapes for a doubly phosphorylated 4E-BP218-62. These results explain some interesting experimental observations, including the low stability of doubly phosphorylated 4E-BP2 and its moderate binding to eIF4E and the inability of phosphorylated Y54A/L59A to fold.
Title: Multifunnel Energy Landscapes for Phosphorylated Translation Repressor 4E-BP2 and Its Mutants.
Study demonstrated key roles for 4E-BP1 and 4E-BP2 during tumor development and during tumor hypoxia. These factors maintain an ability to slow tumor progression in prostate cancer in the face of constitutive mTOR activation arising from loss of PTEN, and are also important in promoting survival of hypoxic cells once cancer has developed
Title: The mTOR Targets 4E-BP1/2 Restrain Tumor Growth and Promote Hypoxia Tolerance in PTEN-driven Prostate Cancer.
Results suggest that IGF2BP3 promotes eIF4E-mediated translational activation through the reduction of EIF4E-BP2 via mRNA degradation, leading to enhanced cell proliferation.
Title: Oncofetal protein IGF2BP3 facilitates the activity of proto-oncogene protein eIF4E through the destabilization of EIF4E-BP2 mRNA.
molecular dynamics simulations to investigate both the folded and unfolded states of 4E-BP2 under different phosphorylation states of T37 and T46
Title: Mechanism of Phosphorylation-Induced Folding of 4E-BP2 Revealed by Molecular Dynamics Simulations.
results highlight stabilization of a phosphorylation-induced fold as the essential mechanism for phospho-regulation of the 4E-BP:eIF4E interaction and exemplify a new mode of biological regulation mediated by intrinsically disordered proteins
Title: Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch.
mTORC1 controls mitochondrial activity and biogenesis by selectively promoting translation of nucleus-encoded mitochondria-related mRNAs via inhibition of the eukaryotic translation initiation factor 4E (eIF4E)-binding proteins (4E-BPs).
Title: mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation.
Data show that the eIF4E binding preference for 4E-BP2 over 4E-BP1 is based on stacking of Arg63 side chain on Trp73 indole ring of eIF4E and construction of hydrophobic space around the Trp73 indole ring by the Leu59-Leu60 sequence of 4E-BP2.
Title: Structural scaffold for eIF4E binding selectivity of 4E-BP isoforms: crystal structure of eIF4E binding region of 4E-BP2 and its comparison with that of 4E-BP1.
Meta-analysis of gene-disease association. (HuGE Navigator)
Title: Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot".

Submit: New GeneRIF Correction See all GeneRIFs (17)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH44583 (e-PCR)
- UniSTS:91139

SHGC-54611 (e-PCR)
- UniSTS:75563

WIAF-2085 (e-PCR)
- UniSTS:68717

D10S1294E (e-PCR)
- UniSTS:47224

WI-14658 (e-PCR)
- UniSTS:13955

D10S2180 (e-PCR)
- UniSTS:64395

D16S325 (e-PCR)
- UniSTS:147089

A001U33 (e-PCR)
- UniSTS:74405

SGC34484 (e-PCR)
- UniSTS:68009

SHGC-30283 (e-PCR)
- UniSTS:76219

D10S1560 (e-PCR)
- UniSTS:68551

EIF4EBP2_623 (e-PCR)
- UniSTS:277198

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables eukaryotic initiation factor 4E binding	IBA Inferred from Biological aspect of Ancestor more info
enables eukaryotic initiation factor 4E binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables translation repressor activity	IDA Inferred from Direct Assay more info	PubMed
enables translation repressor activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in TOR signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in modulation of chemical synaptic transmission	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of translational initiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of translational initiation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of translational initiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
involved_in social behavior	ISS Inferred from Sequence or Structural Similarity more info
involved_in translation	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in intracellular non-membrane-bounded organelle	IDA Inferred from Direct Assay more info	PubMed
is_active_in neuronal ribonucleoprotein granule	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in postsynapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: eukaryotic translation initiation factor 4E-binding protein 2

Names: 4E-BP2; eIF4E-binding protein 2; phosphorylated, heat and acid stable regulated by insulin protein II

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_004096.5 → NP_004087.1 eukaryotic translation initiation factor 4E-binding protein 2

See identical proteins and their annotated locations for NP_004087.1

Status: REVIEWED

Source sequence(s)

AC022532, BC050633, BG717474

Consensus CDS

CCDS7303.1

UniProtKB/Swiss-Prot

Q13542

UniProtKB/TrEMBL

B2R9B9, Q6FG68

Related

ENSP00000362314.4, ENST00000373218.5

Conserved Domains (1) summary

pfam05456
Location:5 → 120

eIF_4EBP; Eukaryotic translation initiation factor 4E binding protein (EIF4EBP)