EIF5A explained

Eukaryotic translation initiation factor 5A-1 is a protein that in humans is encoded by the EIF5A gene.^[1]

It is the only known protein to contain the unusual amino acid hypusine [''N''^ε-(4-amino-2-hydroxybutyl)-lysine], which is synthesized on eIF5A at a specific lysine residue from the polyamine spermidine by two catalytic steps.^[2]

EF-P is the bacterial homolog of eIF5A, which is modified post-translationally in a similar but distinct way.^{[3] [4]} Both proteins are believed to catalyze peptide bond formation and help resolve ribosomal stalls, making them elongation factors despite the "initiation factor" name originally assigned.^[5]

Faundes-Banka syndrome

Germline deleterious heterozygous EIF5A variants cause Faundes-Banka syndrome.^{[6] [7]} This rare human disorder is characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphic features. It was named after Víctor Faundes and Siddharth Banka.

Further reading

• Bevec D, Hauber J . Eukaryotic initiation factor 5A activity and HIV-1 Rev function . Biological Signals . 6 . 3 . 124–133 . 1997 . 9285095 . 10.1159/000109118 .
• Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY . Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions . Cell Research . 15 . 11–12 . 923–934 . 2006 . 16354571 . 10.1038/sj.cr.7290370 . free .
• Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J . Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes . Electrophoresis . 13 . 12 . 960–969 . December 1992 . 1286667 . 10.1002/elps.11501301199 . 41855774 .
• Chung SI, Park MH, Folk JE, Lewis MS . Eukaryotic initiation factor 5A: the molecular form of the hypusine-containing protein from human erythrocytes . Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology . 1076 . 3 . 448–451 . February 1991 . 1900436 . 10.1016/0167-4838(91)90490-q .
• Smit-McBride Z, Dever TE, Hershey JW, Merrick WC . Sequence determination and cDNA cloning of eukaryotic initiation factor 4D, the hypusine-containing protein . The Journal of Biological Chemistry . 264 . 3 . 1578–1583 . January 1989 . 2492279 . 10.1016/S0021-9258(18)94226-2 . free .
• Park MH, Liu TY, Neece SH, Swiggard WJ . Eukaryotic initiation factor 4D. Purification from human red blood cells and the sequence of amino acids around its single hypusine residue . The Journal of Biological Chemistry . 261 . 31 . 14515–14519 . November 1986 . 3095320 . 10.1016/S0021-9258(18)66899-1 . free .
• Koettnitz K, Kappel B, Baumruker T, Hauber J, Bevec D . The genomic structure encoding human initiation factor eIF-5A . Gene . 144 . 2 . 249–252 . July 1994 . 7545941 . 10.1016/0378-1119(94)90385-9 .
• Klier H, Csonga R, Joäo HC, Eckerskorn C, Auer M, Lottspeich F, Eder J . Isolation and structural characterization of different isoforms of the hypusine-containing protein eIF-5A from HeLa cells . Biochemistry . 34 . 45 . 14693–14702 . November 1995 . 7578077 . 10.1021/bi00045a010 .
• Koettnitz K, Wöhl T, Kappel B, Lottspeich F, Hauber J, Bevec D . Identification of a new member of the human eIF-5A gene family . Gene . 159 . 2 . 283–284 . July 1995 . 7622067 . 10.1016/0378-1119(95)00136-T .
• Joe YA, Park MH . Structural features of the eIF-5A precursor required for posttranslational synthesis of deoxyhypusine . The Journal of Biological Chemistry . 269 . 41 . 25916–25921 . October 1994 . 7929297 . 10.1016/S0021-9258(18)47333-4 . free .
• Bevec D, Klier H, Holter W, Tschachler E, Valent P, Lottspeich F, Baumruker T, Hauber J . 6 . Induced gene expression of the hypusine-containing protein eukaryotic initiation factor 5A in activated human T lymphocytes . Proceedings of the National Academy of Sciences of the United States of America . 91 . 23 . 10829–10833 . November 1994 . 7971969 . 45119 . 10.1073/pnas.91.23.10829 . free . 1994PNAS...9110829B .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Ruhl M, Himmelspach M, Bahr GM, Hammerschmid F, Jaksche H, Wolff B, Aschauer H, Farrington GK, Probst H, Bevec D . 6 . Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans-activation . The Journal of Cell Biology . 123 . 6 Pt 1 . 1309–1320 . December 1993 . 8253832 . 2290910 . 10.1083/jcb.123.6.1309 .
• Liu YP, Nemeroff M, Yan YP, Chen KY . Interaction of eukaryotic initiation factor 5A with the human immunodeficiency virus type 1 Rev response element RNA and U6 snRNA requires deoxyhypusine or hypusine modification . Biological Signals . 6 . 3 . 166–174 . 1997 . 9285100 . 10.1159/000109123 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Singh US, Li Q, Cerione R . Identification of the eukaryotic initiation factor 5A as a retinoic acid-stimulated cellular binding partner for tissue transglutaminase II . The Journal of Biological Chemistry . 273 . 4 . 1946–1950 . January 1998 . 9442029 . 10.1074/jbc.273.4.1946 . free .
• Schatz O, Oft M, Dascher C, Schebesta M, Rosorius O, Jaksche H, Dobrovnik M, Bevec D, Hauber J . 6 . Interaction of the HIV-1 rev cofactor eukaryotic initiation factor 5A with ribosomal protein L5 . Proceedings of the National Academy of Sciences of the United States of America . 95 . 4 . 1607–1612 . February 1998 . 9465063 . 19115 . 10.1073/pnas.95.4.1607 . free . 1998PNAS...95.1607S .
• Lee YB, Joe YA, Wolff EC, Dimitriadis EK, Park MH . Complex formation between deoxyhypusine synthase and its protein substrate, the eukaryotic translation initiation factor 5A (eIF5A) precursor . The Biochemical Journal . 340 . 1 . 273–281 . May 1999 . 10229683 . 1220246 . 10.1042/0264-6021:3400273 .

Notes and References

1. Steinkasserer A, Jones T, Sheer D, Koettnitz K, Hauber J, Bevec D . The eukaryotic cofactor for the human immunodeficiency virus type 1 (HIV-1) rev protein, eIF-5A, maps to chromosome 17p12-p13: three eIF-5A pseudogenes map to 10q23.3, 17q25, and 19q13.2 . Genomics . 25 . 3 . 749–752 . February 1995 . 7759117 . 10.1016/0888-7543(95)80025-H .
2. Wolff EC, Kang KR, Kim YS, Park MH . Posttranslational synthesis of hypusine: evolutionary progression and specificity of the hypusine modification . Amino Acids . 33 . 2 . 341–350 . August 2007 . 17476569 . 2572820 . 10.1007/s00726-007-0525-0 .
3. Park JH, Johansson HE, Aoki H, Huang BX, Kim HY, Ganoza MC, Park MH . Post-translational modification by β-lysylation is required for activity of Escherichia coli elongation factor P (EF-P) . The Journal of Biological Chemistry . 287 . 4 . 2579–2590 . January 2012 . 22128152 . 3268417 . 10.1074/jbc.M111.309633 . free .
4. Peil L, Starosta AL, Virumäe K, Atkinson GC, Tenson T, Remme J, Wilson DN . Lys34 of translation elongation factor EF-P is hydroxylated by YfcM . Nature Chemical Biology . 8 . 8 . 695–697 . August 2012 . 22706199 . 10.1038/nchembio.1001 .
5. Rossi D, Kuroshu R, Zanelli CF, Valentini SR . eIF5A and EF-P: two unique translation factors are now traveling the same road . Wiley Interdisciplinary Reviews. RNA . 5 . 2 . 209–222 . 2013 . 24402910 . 10.1002/wrna.1211 . 25447826 .
6. Faundes V, Jennings MD, Crilly S, Legraie S, Withers SE, Cuvertino S, Davies SJ, Douglas AG, Fry AE, Harrison V, Amiel J, Lehalle D, Newman WG, Newkirk P, Ranells J, Splitt M, Cross LA, Saunders CJ, Sullivan BR, Granadillo JL, Gordon CT, Kasher PR, Pavitt GD, Banka S . Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine . Nature Communications . 12 . 1 . 833 . February 2021 . 33547280 . 7864902 . 10.1038/s41467-021-21053-2 . 2021NatCo..12..833F .
7. Web site: OMIM Entry - # 619376 - FAUNDES-BANKA SYNDROME; FABAS . 2022-01-03 . omim.org.