{{cs1 config|name-list-style=vanc|display-authors=6}} {{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Eukaryotic translation initiation factor 4 gamma 1''' is a protein that in humans is encoded by the ''EIF4G1'' gene.<ref name="pmid1429670">{{cite journal | vauthors = Yan R, Rychlik W, Etchison D, Rhoads RE | date = November 1992 | title = Amino acid sequence of the human protein synthesis initiation factor eIF-4 gamma | journal = The Journal of Biological Chemistry | volume = 267 | issue = 32 | pages = 23226–23231 | doi = 10.1016/S0021-9258(18)50080-6 | doi-access = free | pmid = 1429670 }}</ref><ref name="pmid9372926">{{cite journal | vauthors = Imataka H, Sonenberg N | date = December 1997 | title = Human eukaryotic translation initiation factor 4G (eIF4G) possesses two separate and independent binding sites for eIF4A | journal = Molecular and Cellular Biology | volume = 17 | issue = 12 | pages = 6940–6947 | doi = 10.1128/mcb.17.12.6940 | pmc = 232551 | pmid = 9372926 }}</ref>
== Function ==
The protein encoded by this gene is a component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure (carried out by the eIF4A subunit), and recruitment of mRNA to the ribosome. Alternative splicing results in five transcript variants encoding four distinct isoforms.<ref>{{cite web | title = Entrez Gene: EIF4G1 eukaryotic translation initiation factor 4 gamma, 1| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1981}}</ref> eIF4G serves as a scaffold, interacting with mRNA and the other components of the eIF4F complex, as well as the PABP and eIF3. It also facilitates the loading of the small ribosomal subunit onto the mRNA.<ref>{{citation | vauthors = Gentry RC, Ide NA, Comunale VM, Hartwick EW, Kinz-Thompson CD, Gonzalez RL | date = 2023-11-15 | title = The mechanism of mRNA activation | doi = 10.1101/2023.11.15.567265 | pmc = 10680758 | pmid = 38014128 }}</ref>
eIF4G1 controls mitochondrial oxidative phosphorylation, axonal morphogenesis, and memory through promoting translation of select mRNAs, although it has a general role in canonical eukaryotic translation initiation <ref>{{cite journal | vauthors = Kim SH, Choi JH, Marsal-García L, Amiri M, Yanagiya A, Sonenberg N | date = June 2023 | title = The mRNA translation initiation factor eIF4G1 controls mitochondrial oxidative phosphorylation, axonal morphogenesis, and memory | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 120 | issue = 25 | article-number = e2300008120 | doi = 10.1073/pnas.2300008120 | pmc = 10288579 | pmid = 37307456 }}</ref>
== Interactions ==
Eukaryotic translation initiation factor 4 gamma has been shown to interact with MKNK1,<ref name=pmid9878069>{{cite journal | vauthors = Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N | date = January 1999 | title = Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E | journal = The EMBO Journal | volume = 18 | issue = 1 | pages = 270–279 | doi = 10.1093/emboj/18.1.270 | pmc = 1171121 | pmid = 9878069 }}</ref> EIF4A1,<ref name=pmid17353931>{{cite journal | vauthors = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | year = 2007 | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Molecular Systems Biology | volume = 3 | issue = 1 | page = 89 | doi = 10.1038/msb4100134 | pmc = 1847948 | pmid = 17353931 }}</ref><ref name=pmid16648488>{{cite journal | vauthors = Connolly E, Braunstein S, Formenti S, Schneider RJ | date = May 2006 | title = Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells | journal = Molecular and Cellular Biology | volume = 26 | issue = 10 | pages = 3955–3965 | doi = 10.1128/MCB.26.10.3955-3965.2006 | pmc = 1489005 | pmid = 16648488 }}</ref><ref name=pmid16541103>{{cite journal | vauthors = Harris TE, Chi A, Shabanowitz J, Hunt DF, Rhoads RE, Lawrence JC | date = April 2006 | title = mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin | journal = The EMBO Journal | volume = 25 | issue = 8 | pages = 1659–1668 | doi = 10.1038/sj.emboj.7601047 | pmc = 1440840 | pmid = 16541103 }}</ref> EIF4E,<ref name=pmid16648488/><ref name=pmid16541103/><ref name=pmid10600798>{{cite journal | vauthors = Vary TC, Jefferson LS, Kimball SR | date = December 1999 | title = Amino acid-induced stimulation of translation initiation in rat skeletal muscle | journal = The American Journal of Physiology | volume = 277 | issue = 6 Pt 1 | pages = E1077–86 | doi = 10.1152/ajpendo.1999.277.6.E1077 | pmid = 10600798 | s2cid = 4516850 }}</ref><ref name=pmid7651417>{{cite journal | vauthors = Mader S, Lee H, Pause A, Sonenberg N | date = September 1995 | title = The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins | journal = Molecular and Cellular Biology | volume = 15 | issue = 9 | pages = 4990–4997 | doi = 10.1128/MCB.15.9.4990 | pmc = 230746 | pmid = 7651417 }}</ref><ref name=pmid10753870>{{cite journal | vauthors = Kumar V, Sabatini D, Pandey P, Gingras AC, Majumder PK, Kumar M, Yuan ZM, Carmichael G, Weichselbaum R, Sonenberg N, Kufe D, Kharbanda S | date = April 2000 | title = Regulation of the rapamycin and FKBP-target 1/mammalian target of rapamycin and cap-dependent initiation of translation by the c-Abl protein-tyrosine kinase | journal = The Journal of Biological Chemistry | volume = 275 | issue = 15 | pages = 10779–10787 | doi = 10.1074/jbc.275.15.10779 | doi-access = free | pmid = 10753870 }}</ref> MKNK2<ref name=pmid12897141>{{cite journal | vauthors = Scheper GC, Parra JL, Wilson M, Van Kollenburg B, Vertegaal AC, Han ZG, Proud CG | date = August 2003 | title = The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization | journal = Molecular and Cellular Biology | volume = 23 | issue = 16 | pages = 5692–5705 | doi = 10.1128/MCB.23.16.5692-5705.2003 | pmc = 166352 | pmid = 12897141 }}</ref> and PABPC1.<ref name=pmid9857202>{{cite journal | vauthors = Imataka H, Gradi A, Sonenberg N | date = December 1998 | title = A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation | journal = The EMBO Journal | volume = 17 | issue = 24 | pages = 7480–7489 | doi = 10.1093/emboj/17.24.7480 | pmc = 1171091 | pmid = 9857202 }}</ref>
== See also == *Eukaryotic initiation factor
== References == {{reflist}}
== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Gingras AC, Raught B, Sonenberg N | year = 2000 | title = eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation | journal = Annual Review of Biochemistry | volume = 68 | pages = 913–963 | doi = 10.1146/annurev.biochem.68.1.913 | pmid = 10872469 }} * {{cite journal | vauthors = Yan R, Rhoads RE | date = March 1995 | title = Human protein synthesis initiation factor eIF-4 gamma is encoded by a single gene (EIF4G) that maps to chromosome 3q27-qter | journal = Genomics | volume = 26 | issue = 2 | pages = 394–398 | doi = 10.1016/0888-7543(95)80227-D | pmid = 7601469 }} * {{cite journal | vauthors = Mader S, Lee H, Pause A, Sonenberg N | date = September 1995 | title = The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins | journal = Molecular and Cellular Biology | volume = 15 | issue = 9 | pages = 4990–4997 | doi = 10.1128/MCB.15.9.4990 | pmc = 230746 | pmid = 7651417 }} * {{cite journal | vauthors = Pause A, Belsham GJ, Gingras AC, Donzé O, Lin TA, Lawrence JC, Sonenberg N | date = October 1994 | title = Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function | journal = Nature | volume = 371 | issue = 6500 | pages = 762–767 | doi = 10.1038/371762a0 | pmid = 7935836 | bibcode = 1994Natur.371..762P | s2cid = 4360955 }} * {{cite journal | vauthors = Lamphear BJ, Yan R, Yang F, Waters D, Liebig HD, Klump H, Kuechler E, Skern T, Rhoads RE | date = September 1993 | title = Mapping the cleavage site in protein synthesis initiation factor eIF-4 gamma of the 2A proteases from human Coxsackievirus and rhinovirus | journal = The Journal of Biological Chemistry | volume = 268 | issue = 26 | pages = 19200–19203 | doi = 10.1016/S0021-9258(19)36499-3 | doi-access = free | pmid = 8396129 }} * {{cite journal | vauthors = Haghighat A, Mader S, Pause A, Sonenberg N | date = November 1995 | title = Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E | journal = The EMBO Journal | volume = 14 | issue = 22 | pages = 5701–5709 | doi = 10.1002/j.1460-2075.1995.tb00257.x | pmc = 394685 | pmid = 8521827 }} * {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | date = September 1996 | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | doi = 10.1101/gr.6.9.791 | doi-access = free | pmid = 8889548 }} * {{cite journal | vauthors = Lamphear BJ, Rhoads RE | date = December 1996 | title = A single amino acid change in protein synthesis initiation factor 4G renders cap-dependent translation resistant to picornaviral 2A proteases | journal = Biochemistry | volume = 35 | issue = 49 | pages = 15726–15733 | doi = 10.1021/bi961864t | pmid = 8961935 }} * {{cite journal | vauthors = Brass N, Heckel D, Sahin U, Pfreundschuh M, Sybrecht GW, Meese E | date = January 1997 | title = Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma | journal = Human Molecular Genetics | volume = 6 | issue = 1 | pages = 33–39 | doi = 10.1093/hmg/6.1.33 | doi-access = free | pmid = 9002667 }} * {{cite journal | vauthors = Eberle J, Krasagakis K, Orfanos CE | title = Translation initiation factor eIF-4A1 mRNA is consistently overexpressed in human melanoma cells in vitro | journal = International Journal of Cancer | volume = 71 | issue = 3 | pages = 396–401 | date = May 1997 | pmid = 9139875 | doi = 10.1002/(SICI)1097-0215(19970502)71:3<396::AID-IJC16>3.0.CO;2-E | s2cid = 13458929 | doi-access = free }} * {{cite journal | vauthors = Gradi A, Imataka H, Svitkin YV, Rom E, Raught B, Morino S, Sonenberg N | date = January 1998 | title = A novel functional human eukaryotic translation initiation factor 4G | journal = Molecular and Cellular Biology | volume = 18 | issue = 1 | pages = 334–342 | doi = 10.1128/mcb.18.1.334 | pmc = 121501 | pmid = 9418880 }} * {{cite journal | vauthors = Piron M, Vende P, Cohen J, Poncet D | date = October 1998 | title = Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F | journal = The EMBO Journal | volume = 17 | issue = 19 | pages = 5811–5821 | doi = 10.1093/emboj/17.19.5811 | pmc = 1170909 | pmid = 9755181 }} * {{cite journal | vauthors = Imataka H, Gradi A, Sonenberg N | date = December 1998 | title = A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation | journal = The EMBO Journal | volume = 17 | issue = 24 | pages = 7480–7489 | doi = 10.1093/emboj/17.24.7480 | pmc = 1171091 | pmid = 9857202 }} * {{cite journal | vauthors = Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N | date = January 1999 | title = Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E | journal = The EMBO Journal | volume = 18 | issue = 1 | pages = 270–279 | doi = 10.1093/emboj/18.1.270 | pmc = 1171121 | pmid = 9878069 }} * {{cite journal | vauthors = Laroia G, Cuesta R, Brewer G, Schneider RJ | date = April 1999 | title = Control of mRNA decay by heat shock-ubiquitin-proteasome pathway | journal = Science | volume = 284 | issue = 5413 | pages = 499–502 | doi = 10.1126/science.284.5413.499 | pmid = 10205060 | bibcode = 1999Sci...284..499L }} * {{cite journal | vauthors = Vary TC, Jefferson LS, Kimball SR | date = December 1999 | title = Amino acid-induced stimulation of translation initiation in rat skeletal muscle | journal = The American Journal of Physiology | volume = 277 | issue = 6 Pt 1 | pages = E1077–86 | doi = 10.1152/ajpendo.1999.277.6.E1077 | pmid = 10600798 | s2cid = 4516850 }} * {{cite journal | vauthors = Cuesta R, Laroia G, Schneider RJ | date = June 2000 | title = Chaperone hsp27 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes | journal = Genes & Development | volume = 14 | issue = 12 | pages = 1460–1470 | doi = 10.1101/gad.14.12.1460 | pmc = 316692 | pmid = 10859165 }} * {{cite journal | vauthors = Chartier-Harlin MC, Dachsel JC, Vilariño-Güell C, Lincoln SJ, Leprêtre F, Hulihan MM, Kachergus J, Milnerwood AJ, Tapia L, Song MS, Le Rhun E, Mutez E, Larvor L, Duflot A, Vanbesien-Mailliot C, Kreisler A, Ross OA, Nishioka K, Soto-Ortolaza AI, Cobb SA, Melrose HL, Behrouz B, Keeling BH, Bacon JA, Hentati E, Williams L, Yanagiya A, Sonenberg N, Lockhart PJ, Zubair AC, Uitti RJ, Aasly JO, Krygowska-Wajs A, Opala G, Wszolek ZK, Frigerio R, Maraganore DM, Gosal D, Lynch T, Hutchinson M, Bentivoglio AR, Valente EM, Nichols WC, Pankratz N, Foroud T, Gibson RA, Hentati F, Dickson DW, Destée A, Farrer MJ | date = September 2011 | title = Translation initiator EIF4G1 mutations in familial Parkinson disease | journal = American Journal of Human Genetics | volume = 89 | issue = 3 | pages = 398–406 | doi = 10.1016/j.ajhg.2011.08.009 | pmc = 3169825 | pmid = 21907011 }} {{refend}}
{{PDB Gallery|geneid=1981}}
{{Initiation factors}}