EIF4G2

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc}} {{Infobox_gene}} '''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.<ref name="pmid9030685">{{cite journal | vauthors = Yamanaka S, Poksay KS, Arnold KS, Innerarity TL | title = A novel translational repressor mRNA is edited extensively in livers containing tumors caused by the transgene expression of the apoB mRNA-editing enzyme | journal = Genes Dev. | volume = 11 | issue = 3 | pages = 321–33 | date = March 1997 | pmid = 9030685 | doi = 10.1101/gad.11.3.321 | doi-access = free }}</ref><ref name="pmid9032289">{{cite journal | vauthors = Levy-Strumpf N, Deiss LP, Berissi H, Kimchi A | title = DAP-5, a novel homolog of eukaryotic translation initiation factor 4G isolated as a putative modulator of gamma interferon-induced programmed cell death | journal = Mol. Cell. Biol. | volume = 17 | issue = 3 | pages = 1615–25 | date = March 1997 | pmid = 9032289 | pmc = 231887 | doi = 10.1128/mcb.17.3.1615}}</ref>

== 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. Other studies have shown that eIF4G2 can promote re-initiation and translation of the main ORF on uORF-containing mRNAs <ref>{{cite journal | vauthors = Weber R, Kleemann L, Hirschberg I, Chung MY, Valkov E, Igreja C | date = December 2022 | title = DAP5 enables main ORF translation on mRNAs with structured and uORF-containing 5' leaders | journal = Nature Communications | volume = 13 | issue = 1 | pages = 7510 | doi = 10.1038/s41467-022-35019-5 | pmc = 9726905 | pmid = 36473845 }}</ref> 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.<ref name="entrez">{{cite web | title = Entrez Gene: EIF4G2 eukaryotic translation initiation factor 4 gamma, 2| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1982}}</ref>

== Interactions ==

EIF4G2 has been shown to interact with EIF3A.<ref name="pmid9418880">{{cite journal | vauthors = Gradi A, Imataka H, Svitkin YV, Rom E, Raught B, Morino S, Sonenberg N | title = A novel functional human eukaryotic translation initiation factor 4G | journal = Mol. Cell. Biol. | volume = 18 | issue = 1 | pages = 334–42 | date = January 1998 | pmid = 9418880 | pmc = 121501 | doi=10.1128/mcb.18.1.334}}</ref><ref name=pmid10611228>{{cite journal | vauthors = Henis-Korenblit S, Strumpf NL, Goldstaub D, Kimchi A | title = A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site-mediated translation | journal = Mol. Cell. Biol. | volume = 20 | issue = 2 | pages = 496–506 | date = January 2000 | pmid = 10611228 | pmc = 85113 | doi = 10.1128/MCB.20.2.496-506.2000 }}</ref>

== References == {{reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | year = 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{cite journal | vauthors = Shaughnessy JD, Jenkins NA, Copeland NG | title = cDNA cloning, expression analysis, and chromosomal localization of a gene with high homology to wheat eIF-(iso)4F and mammalian eIF-4G | journal = Genomics | volume = 39 | issue = 2 | pages = 192–7 | year = 1997 | pmid = 9027506 | doi = 10.1006/geno.1996.4502 | url = https://zenodo.org/record/1229713 }} * {{cite journal | vauthors = Imataka H, Olsen HS, Sonenberg N | title = A new translational regulator with homology to eukaryotic translation initiation factor 4G | journal = EMBO J. | volume = 16 | issue = 4 | pages = 817–25 | year = 1997 | pmid = 9049310 | pmc = 1169682 | doi = 10.1093/emboj/16.4.817 }} * {{cite journal | vauthors = Imataka H, Sonenberg N | title = Human eukaryotic translation initiation factor 4G (eIF4G) possesses two separate and independent binding sites for eIF4A | journal = Mol. Cell. Biol. | volume = 17 | issue = 12 | pages = 6940–7 | year = 1997 | pmid = 9372926 | pmc = 232551 | doi = 10.1128/mcb.17.12.6940}} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | year = 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }} * {{cite journal | vauthors = Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N | title = Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E | journal = EMBO J. | volume = 18 | issue = 1 | pages = 270–9 | year = 1999 | pmid = 9878069 | pmc = 1171121 | doi = 10.1093/emboj/18.1.270 }} * {{cite journal | vauthors = Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK | title = Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G | journal = Mol. Cell | volume = 3 | issue = 6 | pages = 707–16 | year = 1999 | pmid = 10394359 | doi = 10.1016/S1097-2765(01)80003-4 | doi-access = free }} * {{cite journal | vauthors = Henis-Korenblit S, Strumpf NL, Goldstaub D, Kimchi A | title = A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site-mediated translation | journal = Mol. Cell. Biol. | volume = 20 | issue = 2 | pages = 496–506 | year = 2000 | pmid = 10611228 | pmc = 85113 | doi = 10.1128/MCB.20.2.496-506.2000 }} * {{cite journal | vauthors = Marcotrigiano J, Lomakin IB, Sonenberg N, Pestova TV, Hellen CU, Burley SK | title = A conserved HEAT domain within eIF4G directs assembly of the translation initiation machinery | journal = Mol. Cell | volume = 7 | issue = 1 | pages = 193–203 | year = 2001 | pmid = 11172724 | doi = 10.1016/S1097-2765(01)00167-8 | doi-access = free }} * {{cite journal | vauthors = Marissen WE, Gradi A, Sonenberg N, Lloyd RE | title = Cleavage of eukaryotic translation initiation factor 4GII correlates with translation inhibition during apoptosis | journal = Cell Death Differ. | volume = 7 | issue = 12 | pages = 1234–43 | year = 2000 | pmid = 11175261 | doi = 10.1038/sj.cdd.4400750 | doi-access = free }} * {{cite journal | vauthors = Asano K, Shalev A, Phan L, Nielsen K, Clayton J, Valásek L, Donahue TF, Hinnebusch AG | title = Multiple roles for the C-terminal domain of eIF5 in translation initiation complex assembly and GTPase activation | journal = EMBO J. | volume = 20 | issue = 9 | pages = 2326–37 | year = 2001 | pmid = 11331597 | pmc = 125443 | doi = 10.1093/emboj/20.9.2326 }} * {{cite journal | vauthors = Pyronnet S, Dostie J, Sonenberg N | title = Suppression of cap-dependent translation in mitosis | journal = Genes Dev. | volume = 15 | issue = 16 | pages = 2083–93 | year = 2001 | pmid = 11511540 | pmc = 312759 | doi = 10.1101/gad.889201 }} * {{cite journal | vauthors = Henis-Korenblit S, Shani G, Sines T, Marash L, Shohat G, Kimchi A | title = The caspase-cleaved DAP5 protein supports internal ribosome entry site-mediated translation of death proteins | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 8 | pages = 5400–5 | year = 2002 | pmid = 11943866 | pmc = 122781 | doi = 10.1073/pnas.082102499 | doi-access = free | bibcode = 2002PNAS...99.5400H }} * {{cite journal | vauthors = Perales C, Carrasco L, Ventoso I | title = Cleavage of eIF4G by HIV-1 protease: effects on translation | journal = FEBS Lett. | volume = 533 | issue = 1–3 | pages = 89–94 | year = 2003 | pmid = 12505164 | doi = 10.1016/S0014-5793(02)03764-X | s2cid = 35982071 | doi-access = free | bibcode = 2003FEBSL.533...89P }} * {{cite journal | vauthors = Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J | title = Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides | journal = Nat. Biotechnol. | volume = 21 | issue = 5 | pages = 566–9 | year = 2003 | pmid = 12665801 | doi = 10.1038/nbt810 | s2cid = 23783563 }} * {{cite journal | vauthors = Li Z, Hu CY, Mo BQ, Xu JD, Zhao Y | title = [Effect of beta-carotene on gene expression of breast cancer cells] | journal = AI Zheng | volume = 22 | issue = 4 | pages = 380–4 | year = 2003 | pmid = 12703993 }} * {{cite journal | vauthors = Qin H, Raught B, Sonenberg N, Goldstein EG, Edelman AM | title = Phosphorylation screening identifies translational initiation factor 4GII as an intracellular target of Ca(2+)/calmodulin-dependent protein kinase I | journal = J. Biol. Chem. | volume = 278 | issue = 49 | pages = 48570–9 | year = 2003 | pmid = 14507913 | doi = 10.1074/jbc.M308781200 | doi-access = free }} {{refend}}