EIF4G2

Last updated

EIF4G2
Protein EIF4G2 PDB 3D3M.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases EIF4G2 , AAG1, DAP5, NAT1, P97, eukaryotic translation initiation factor 4 gamma 2
External IDs OMIM: 602325; MGI: 109207; HomoloGene: 37477; GeneCards: EIF4G2; OMA:EIF4G2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001418
NM_001042559
NM_001172705

NM_001040131
NM_013507

RefSeq (protein)

NP_001036024
NP_001166176
NP_001409

NP_001035221
NP_038535

Location (UCSC) Chr 11: 10.8 – 10.81 Mb Chr 7: 110.67 – 110.68 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Eukaryotic translation initiation factor 4 gamma 2 (also called p97, NAT1, and DAP-5) is a protein that in humans is encoded by the EIF4G2 gene. [5] [6]

Contents

Function

Translation initiation is mediated by specific recognition of the cap structure by eukaryotic translation initiation factor 4F (eIF4F), which is a cap binding protein complex that consists of three subunits: eIF4A, eIF4E and eIF4G. The protein encoded by the eIF4G2 gene shares similarity with the C-terminal region of eIF4G1 that contains the binding sites for eIF4A and eIF3. eIF4G2 additionally contains a binding site for eIF4E at the N-terminus. Unlike eIF4G1, which supports cap-dependent and independent translation, the eIF4G2 gene product functions as a general repressor of translation by forming translationally inactive complexes. In vitro and in vivo studies indicate that translation of this mRNA initiates exclusively at a non-AUG (GUG) codon. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. [7]

Interactions

EIF4G2 has been shown to interact with EIF3A. [8] [9]

Related Research Articles

In molecular biology, the five-prime cap is a specially altered nucleotide on the 5′ end of some primary transcripts such as precursor messenger RNA. This process, known as mRNA capping, is highly regulated and vital in the creation of stable and mature messenger RNA able to undergo translation during protein synthesis. Mitochondrial mRNA and chloroplastic mRNA are not capped.

An internal ribosome entry site, abbreviated IRES, is an RNA element that allows for translation initiation in a cap-independent manner, as part of the greater process of protein synthesis. Initiation of eukaryotic translation nearly always occurs at and is dependent on the 5' cap of mRNA molecules, where the translation initiation complex forms and ribosomes engage the mRNA. IRES elements, however allow ribosomes to engage the mRNA and begin translation independently of the 5' cap.

Eukaryotic translation is the biological process by which messenger RNA is translated into proteins in eukaryotes. It consists of four phases: initiation, elongation, termination, and recapping.

In molecular biology, initiation factors are proteins that bind to the small subunit of the ribosome during the initiation of translation, a part of protein biosynthesis.

Eukaryotic initiation factors (eIFs) are proteins or protein complexes involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of ribosomal preinitiation complexes around the start codon and are an important input for post-transcription gene regulation. Several initiation factors form a complex with the small 40S ribosomal subunit and Met-tRNAiMet called the 43S preinitiation complex. Additional factors of the eIF4F complex recruit the 43S PIC to the five-prime cap structure of the mRNA, from which the 43S particle scans 5'-->3' along the mRNA to reach an AUG start codon. Recognition of the start codon by the Met-tRNAiMet promotes gated phosphate and eIF1 release to form the 48S preinitiation complex, followed by large 60S ribosomal subunit recruitment to form the 80S ribosome. There exist many more eukaryotic initiation factors than prokaryotic initiation factors, reflecting the greater biological complexity of eukaryotic translation. There are at least twelve eukaryotic initiation factors, composed of many more polypeptides, and these are described below.

<span class="mw-page-title-main">Hepatitis A virus internal ribosome entry site (IRES)</span>

This family represents the internal ribosome entry site (IRES) of the hepatitis A virus. HAV IRES is a 450 nucleotide long sequence located in the 735 nt long 5’ UTR of Hepatitis A viral RNA genome. IRES elements allow cap and end-independent translation of mRNA in the host cell. The IRES achieves this by mediating the internal initiation of translation by recruiting a ribosomal 40S pre-initiation complex directly to the initiation codon and eliminates the requirement for eukaryotic initiation factor, eIF4F.

<span class="mw-page-title-main">EIF4EBP1</span> Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 4E-binding protein 1 is a protein that in humans is encoded by the EIF4EBP1 gene. inhibits cap-dependent translation by binding to translation initiation factor eIF4E. Phosphorylation of 4E-BP1 results in its release from eIF4E, thereby allows cap-dependent translation to continue thereby increasing the rate of protein synthesis.

<span class="mw-page-title-main">PABPC1</span> Protein-coding gene in the species Homo sapiens

Polyadenylate-binding protein 1 is a protein that in humans is encoded by the PABPC1 gene. The protein PABP1 binds mRNA and facilitates a variety of functions such as transport into and out of the nucleus, degradation, translation, and stability. There are two separate PABP1 proteins, one which is located in the nucleus (PABPN1) and the other which is found in the cytoplasm (PABPC1). The location of PABP1 affects the role of that protein and its function with RNA.

<span class="mw-page-title-main">EIF4E</span> Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein that in humans is encoded by the EIF4E gene.

<span class="mw-page-title-main">Eukaryotic translation initiation factor 4 gamma 1</span> Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 4 gamma 1 is a protein that in humans is encoded by the EIF4G1 gene.

<span class="mw-page-title-main">EIF3A</span> Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 3 subunit A (eIF3a) is a protein that in humans is encoded by the EIF3A gene. It is one of the subunits of Eukaryotic initiation factor 3 (eIF3) a multiprotein complex playing major roles in translation initiation in eukaryotes.

<span class="mw-page-title-main">MKNK1</span> Protein-coding gene in the species Homo sapiens

MAP kinase-interacting serine/threonine-protein kinase 1 is an enzyme that in humans is encoded by the MKNK1 gene.

<span class="mw-page-title-main">EIF4G3</span> Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 4 gamma 3 is a protein that in humans is encoded by the EIF4G3 gene. The gene encodes a protein that functions in translation by aiding the assembly of the ribosome onto the messenger RNA template. Confusingly, this protein is usually referred to as eIF4GII, as although EIF4G3 is the third gene that is similar to eukaryotic translation initiation factor 4 gamma, the second isoform EIF4G2 is not an active translation initiation factor.

<span class="mw-page-title-main">EIF4A1</span> Protein coding gene in Humans

Eukaryotic initiation factor 4A-I is a 46 kDa cytosolic protein that, in humans, is encoded by the EIF4A1 gene, which is located on chromosome 17. It is the most prevalent member of the eIF4A family of ATP-dependant RNA helicases, and plays a critical role in the initiation of cap-dependent eukaryotic protein translation as a component of the eIF4F translation initiation complex. eIF4A1 unwinds the secondary structure of RNA within the 5'-UTR of mRNA, a critical step necessary for the recruitment of the 43S preinitiation complex, and thus the translation of protein in eukaryotes. It was first characterized in 1982 by Grifo, et al., who purified it from rabbit reticulocyte lysate.

<span class="mw-page-title-main">EIF4B</span> Protein-coding gene in humans

Eukaryotic translation initiation factor 4B is a protein that in humans is encoded by the EIF4B gene.

<span class="mw-page-title-main">EIF4EBP2</span> Protein-coding gene in humans

Eukaryotic translation initiation factor 4E-binding protein 2 is a protein that in humans is encoded by the EIF4EBP2 gene.

<span class="mw-page-title-main">PAIP1</span> Protein-coding gene in the species Homo sapiens

Polyadenylate-binding protein-interacting protein 1 is a protein that in humans is encoded by the PAIP1 gene.

<span class="mw-page-title-main">EIF4A2</span> Protein-coding gene in the species Homo sapiens

Eukaryotic initiation factor 4A-II is a protein that in humans is encoded by the EIF4A2 gene.

Eukaryotic translation initiation factor 4 G (eIF4G) is a protein involved in eukaryotic translation initiation and is a component of the eIF4F cap-binding complex. Orthologs of eIF4G have been studied in multiple species, including humans, yeast, and wheat. However, eIF4G is exclusively found in domain Eukarya, and not in domains Bacteria or Archaea, which do not have capped mRNA. As such, eIF4G structure and function may vary between species, although the human EIF4G1 has been the focus of extensive studies.

The eukaryotic initiation factor-4A (eIF4A) family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits. In addition these proteins are helicases that function to unwind double-stranded RNA.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000110321 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000005610 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Yamanaka S, Poksay KS, Arnold KS, Innerarity TL (March 1997). "A novel translational repressor mRNA is edited extensively in livers containing tumors caused by the transgene expression of the apoB mRNA-editing enzyme". Genes Dev. 11 (3): 321–33. doi: 10.1101/gad.11.3.321 . PMID   9030685.
  6. Levy-Strumpf N, Deiss LP, Berissi H, Kimchi A (March 1997). "DAP-5, a novel homolog of eukaryotic translation initiation factor 4G isolated as a putative modulator of gamma interferon-induced programmed cell death". Mol. Cell. Biol. 17 (3): 1615–25. doi:10.1128/mcb.17.3.1615. PMC   231887 . PMID   9032289.
  7. "Entrez Gene: EIF4G2 eukaryotic translation initiation factor 4 gamma, 2".
  8. Gradi A, Imataka H, Svitkin YV, Rom E, Raught B, Morino S, Sonenberg N (January 1998). "A novel functional human eukaryotic translation initiation factor 4G". Mol. Cell. Biol. 18 (1): 334–42. doi:10.1128/mcb.18.1.334. PMC   121501 . PMID   9418880.
  9. Henis-Korenblit S, Strumpf NL, Goldstaub D, Kimchi A (January 2000). "A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site-mediated translation". Mol. Cell. Biol. 20 (2): 496–506. doi:10.1128/MCB.20.2.496-506.2000. PMC   85113 . PMID   10611228.

Further reading