Eukaryotic translation initiation factor 4E

Details

Name
Eukaryotic translation initiation factor 4E
Synonyms
  • eIF-4E
  • eIF-4F 25 kDa subunit
  • EIF4EL1
  • EIF4F
  • mRNA cap-binding protein
Gene Name
EIF4E
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001905|Eukaryotic translation initiation factor 4E
MATVEPETTPTPNPPTTEEEKTESNQEVANPEHYIKHPLQNRWALWFFKNDKSKTWQANL
RLISKFDTVEDFWALYNHIQLSSNLMPGCDYSLFKDGIEPMWEDEKNKRGGRWLITLNKQ
QRRSDLDRFWLETLLCLIGESFDDYSDDVCGAVVNVRAKGDKIAIWTTECENREAVTHIG
RVYKERLGLPPKIVIGYQSHADTATKSGSTTKNRFVV
Number of residues
217
Molecular Weight
25097.07
Theoretical pI
6.04
GO Classification
Functions
enzyme binding / eukaryotic initiation factor 4G binding / poly(A) RNA binding / repressing transcription factor binding / RNA cap binding / translation initiation factor activity
Processes
behavioral fear response / cellular protein metabolic process / cytokine-mediated signaling pathway / G1/S transition of mitotic cell cycle / gene expression / insulin receptor signaling pathway / mRNA export from nucleus / negative regulation of neuron differentiation / negative regulation of translation / nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay / nuclear-transcribed mRNA poly(A) tail shortening / positive regulation of mitotic cell cycle / regulation of translation / stem cell population maintenance / translation / translational initiation / viral process
Components
chromatoid body / cytoplasm / cytoplasmic mRNA processing body / cytoplasmic stress granule / cytosol / eukaryotic translation initiation factor 4F complex / extracellular exosome / mRNA cap binding complex / perinuclear region of cytoplasm / RISC complex
General Function
Translation initiation factor activity
Specific Function
Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010673|Eukaryotic translation initiation factor 4E (EIF4E)
ATGTTGGACCTGACCTCCCGCGGACAAGTGGGGACGTCCCGGAGGATGGCCGAGGCGGCG
TGTAGCGCACACTTTCTGGAAACCACCCCTACTCCTAATCCCCCGACTACAGAAGAGGAG
AAAACGGAATCTAATCAGGAGGTTGCTAACCCAGAACACTATATTAAACATCCCCTACAG
AACAGATGGGCACTCTGGTTTTTTAAAAATGATAAAAGCAAAACTTGGCAAGCAAACCTG
CGGCTGATCTCCAAGTTTGATACTGTTGAAGACTTTTGGGCTCTGTACAACCATATCCAG
TTGTCTAGTAATTTAATGCCTGGCTGTGACTACTCACTTTTTAAGGATGGTATTGAGCCT
ATGTGGGAAGATGAGAAAAACAAACGGGGAGGACGATGGCTAATTACATTGAACAAACAG
CAGAGACGAAGTGACCTCGATCGCTTTTGGCTAGAGACACTTCTGTGCCTTATTGGAGAA
TCTTTTGATGACTACAGTGATGATGTATGTGGCGCTGTTGTTAATGTTAGAGCTAAAGGT
GATAAGATAGCAATATGGACTACTGAATGTGAAAACAGAGAAGCTGTTACACATATAGGG
AGGGTATACAAGGAAAGGTTAGGACTTCCTCCAAAGATAGTGATTGGTTATCAGTCCCAC
GCAGACACAGCTACTAAGAGCGGCTCCACCACTAAAAATAGGTTTGTTGTTTAA
Chromosome Location
4
Locus
4q21-q25
External Identifiers
ResourceLink
UniProtKB IDP06730
UniProtKB Entry NameIF4E_HUMAN
GenBank Protein ID306487
GenBank Gene IDM15353
GenAtlas IDEIF4E
HGNC IDHGNC:3287
General References
  1. Rychlik W, Domier LL, Gardner PR, Hellmann GM, Rhoads RE: Amino acid sequence of the mRNA cap-binding protein from human tissues. Proc Natl Acad Sci U S A. 1987 Feb;84(4):945-9. [PubMed:3469651]
  2. Rychlik W, Domier LL, Gardner PR, Hellmann GM, Rhoads RE: Amino acid sequence of the mRNA cap-binding protein from human tissues. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1148. [PubMed:1736299]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  4. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  6. Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS: Transcriptome analysis of human gastric cancer. Mamm Genome. 2005 Dec;16(12):942-54. Epub 2005 Dec 8. [PubMed:16341674]
  7. Marino MW, Feld LJ, Jaffe EA, Pfeffer LM, Han HM, Donner DB: Phosphorylation of the proto-oncogene product eukaryotic initiation factor 4E is a common cellular response to tumor necrosis factor. J Biol Chem. 1991 Feb 15;266(5):2685-8. [PubMed:1993647]
  8. Ueda H, Iyo H, Doi M, Inoue M, Ishida T, Morioka H, Tanaka T, Nishikawa S, Uesugi S: Combination of Trp and Glu residues for recognition of mRNA cap structure. Analysis of m7G base recognition site of human cap binding protein (IF-4E) by site-directed mutagenesis. FEBS Lett. 1991 Mar 25;280(2):207-10. [PubMed:1672854]
  9. Rychlik W, Russ MA, Rhoads RE: Phosphorylation site of eukaryotic initiation factor 4E. J Biol Chem. 1987 Aug 5;262(22):10434-7. [PubMed:3112145]
  10. Kaufman RJ, Murtha-Riel P, Pittman DD, Davies MV: Characterization of wild-type and Ser53 mutant eukaryotic initiation factor 4E overexpression in mammalian cells. J Biol Chem. 1993 Jun 5;268(16):11902-9. [PubMed:8505316]
  11. Zhang Y, Klein HL, Schneider RJ: Role of Ser-53 phosphorylation in the activity of human translation initiation factor eIF-4E in mammalian and yeast cells. Gene. 1995 Oct 3;163(2):283-8. [PubMed:7590282]
  12. Joshi B, Cai AL, Keiper BD, Minich WB, Mendez R, Beach CM, Stepinski J, Stolarski R, Darzynkiewicz E, Rhoads RE: Phosphorylation of eukaryotic protein synthesis initiation factor 4E at Ser-209. J Biol Chem. 1995 Jun 16;270(24):14597-603. [PubMed:7782323]
  13. Flynn A, Proud CG: Serine 209, not serine 53, is the major site of phosphorylation in initiation factor eIF-4E in serum-treated Chinese hamster ovary cells. J Biol Chem. 1995 Sep 15;270(37):21684-8. [PubMed:7665584]
  14. Haghighat A, Mader S, Pause A, Sonenberg N: Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J. 1995 Nov 15;14(22):5701-9. [PubMed:8521827]
  15. Dostie J, Ferraiuolo M, Pause A, Adam SA, Sonenberg N: A novel shuttling protein, 4E-T, mediates the nuclear import of the mRNA 5' cap-binding protein, eIF4E. EMBO J. 2000 Jun 15;19(12):3142-56. [PubMed:10856257]
  16. Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N: Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. EMBO J. 1999 Jan 4;18(1):270-9. [PubMed:9878069]
  17. Li W, Belsham GJ, Proud CG: Eukaryotic initiation factors 4A (eIF4A) and 4G (eIF4G) mutually interact in a 1:1 ratio in vivo. J Biol Chem. 2001 Aug 3;276(31):29111-5. Epub 2001 Jun 14. [PubMed:11408474]
  18. Scheper GC, Morrice NA, Kleijn M, Proud CG: The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells. Mol Cell Biol. 2001 Feb;21(3):743-54. [PubMed:11154262]
  19. Scheper GC, Parra JL, Wilson M, Van Kollenburg B, Vertegaal AC, Han ZG, Proud CG: The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization. Mol Cell Biol. 2003 Aug;23(16):5692-705. [PubMed:12897141]
  20. Wichroski MJ, Robb GB, Rana TM: Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies. PLoS Pathog. 2006 May;2(5):e41. Epub 2006 May 12. [PubMed:16699599]
  21. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330]
  22. Neves-Pereira M, Muller B, Massie D, Williams JH, O'Brien PC, Hughes A, Shen SB, Clair DS, Miedzybrodzka Z: Deregulation of EIF4E: a novel mechanism for autism. J Med Genet. 2009 Nov;46(11):759-65. doi: 10.1136/jmg.2009.066852. Epub 2009 Jun 25. [PubMed:19556253]
  23. Burrows C, Abd Latip N, Lam SJ, Carpenter L, Sawicka K, Tzolovsky G, Gabra H, Bushell M, Glover DM, Willis AE, Blagden SP: The RNA binding protein Larp1 regulates cell division, apoptosis and cell migration. Nucleic Acids Res. 2010 Sep;38(16):5542-53. doi: 10.1093/nar/gkq294. Epub 2010 Apr 29. [PubMed:20430826]
  24. James V, Zhang Y, Foxler DE, de Moor CH, Kong YW, Webb TM, Self TJ, Feng Y, Lagos D, Chu CY, Rana TM, Morley SJ, Longmore GD, Bushell M, Sharp TV: LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12499-504. doi: 10.1073/pnas.0914987107. Epub 2010 Jun 28. [PubMed:20616046]
  25. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  26. Yanagiya A, Suyama E, Adachi H, Svitkin YV, Aza-Blanc P, Imataka H, Mikami S, Martineau Y, Ronai ZA, Sonenberg N: Translational homeostasis via the mRNA cap-binding protein, eIF4E. Mol Cell. 2012 Jun 29;46(6):847-58. doi: 10.1016/j.molcel.2012.04.004. Epub 2012 May 10. [PubMed:22578813]
  27. Lukhele S, Bah A, Lin H, Sonenberg N, Forman-Kay JD: Interaction of the eukaryotic initiation factor 4E with 4E-BP2 at a dynamic bipartite interface. Structure. 2013 Dec 3;21(12):2186-96. doi: 10.1016/j.str.2013.08.030. Epub 2013 Oct 24. [PubMed:24207126]
  28. Bah A, Vernon RM, Siddiqui Z, Krzeminski M, Muhandiram R, Zhao C, Sonenberg N, Kay LE, Forman-Kay JD: Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch. Nature. 2015 Mar 5;519(7541):106-9. doi: 10.1038/nature13999. Epub 2014 Dec 22. [PubMed:25533957]
  29. Tomoo K, Shen X, Okabe K, Nozoe Y, Fukuhara S, Morino S, Ishida T, Taniguchi T, Hasegawa H, Terashima A, Sasaki M, Katsuya Y, Kitamura K, Miyoshi H, Ishikawa M, Miura K: Crystal structures of 7-methylguanosine 5'-triphosphate (m(7)GTP)- and P(1)-7-methylguanosine-P(3)-adenosine-5',5'-triphosphate (m(7)GpppA)-bound human full-length eukaryotic initiation factor 4E: biological importance of the C-terminal flexible region. Biochem J. 2002 Mar 15;362(Pt 3):539-44. [PubMed:11879179]
  30. Miura T, Shiratori Y, Shimma N: Backbone resonance assignment of human eukaryotic translation initiation factor 4E (eIF4E) in complex with 7-methylguanosine diphosphate (m7GDP) and a 17-amino acid peptide derived from human eIF4GII. J Biomol NMR. 2003 Nov;27(3):279-80. [PubMed:12975586]
  31. Tomoo K, Matsushita Y, Fujisaki H, Abiko F, Shen X, Taniguchi T, Miyagawa H, Kitamura K, Miura K, Ishida T: Structural basis for mRNA Cap-Binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods. Biochim Biophys Acta. 2005 Dec 1;1753(2):191-208. Epub 2005 Aug 24. [PubMed:16271312]
  32. Volpon L, Osborne MJ, Topisirovic I, Siddiqui N, Borden KL: Cap-free structure of eIF4E suggests a basis for conformational regulation by its ligands. EMBO J. 2006 Nov 1;25(21):5138-49. Epub 2006 Oct 12. [PubMed:17036047]
  33. Brown CJ, McNae I, Fischer PM, Walkinshaw MD: Crystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives. J Mol Biol. 2007 Sep 7;372(1):7-15. Epub 2007 Jun 15. [PubMed:17631896]
  34. Fukuyo A, In Y, Ishida T, Tomoo K: 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. J Pept Sci. 2011 Sep;17(9):650-7. doi: 10.1002/psc.1384. Epub 2011 Jun 10. [PubMed:21661078]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB016497-methyl-GpppAexperimentalunknownDetails
DB019607-methyl-7,8-dihydroguanosine-5'-diphosphateexperimentalunknownDetails
DB027167-methyl-guanosine-5'-triphosphateexperimentalunknownDetails
DB05165LY2275796investigationalunknownDetails
DB08217S-[(1-Hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl] methanesulfonothioateexperimentalunknownDetails