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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Inteins


High impact information on Inteins

  • This review focuses on the mechanisms underlying biogenesis of the mature Hh proteins, which are dually modified by cholesteryl and palmitoyl adducts, as well as on the relationship between Hh proteins and the self-splicing proteins (i.e., proteins containing inteins) and the Hh-like proteins of nematodes [6].
  • The conserved Ser or Cys at the intein N-terminus and the conserved intein penultimate His are absent in the KlbA family of inteins [7].
  • Protein splicing of the yeast TFP1 intervening protein sequence: a model for self-excision [8].
  • We have synthesized artificial genes that encode for N-terminal half (Int-n) and C-terminal half (Int-c) fragments of Ssp DnaE split intein and divided beta-glucuronidase (GUS) gene to encode GUS-n and GUS-c parts of the enzyme as reporter [9].
  • Although apparently unrelated evolutionarily, Nup98 has converged on an autoproteolytic biogenesis mechanism similar to that of hedgehog proteins, the inteins, and the N-terminal nucleophile proteins [10].

Chemical compound and disease context of Inteins


Biological context of Inteins

  • The downstream bnrdE exon harbors an intervening sequence not excised at the level of the primary transcript, which encodes an in-frame polypeptide displaying all the features of an intein [14].
  • Cyclization of this residue to succinimide causes the final detachment of inteins from their hosts [15].
  • Both recombinant inteins exhibit endonuclease activity, with an optimal temperature of 70 degrees C. The Tfu pol-1 intein, which belongs to the Psp KOD pol-1 allelic family, recognizes and cleaves a minimal sequence of 16 base pairs (bp) on supercoiled DNA with either Mn(2+) or Mg(2+) as cofactor [16].
  • Three inteins were found when analyzing a pair of split dnaE genes encoding the catalytic subunit of DNA polymerase III in the oceanic N2-fixing cyanobacterium Trichodesmium erythraeum [17].
  • The FKBP and FRB domains, which are dimerized by rapamycin and thereby induce the reconstitution of the split intein, were fused to the extein sequences of the split intein halves [18].

Anatomical context of Inteins


Associations of Inteins with chemical compounds


Gene context of Inteins

  • In addition, bnrdE provides an example of a group I intron and an intein coding sequence within the same gene [14].
  • We show that a 113 residue truncated Ho-endonuclease starting at intein motif C initiates a mating type switch in yeast [24].
  • CONCLUSION: The repairing system working in intein homing shares molecular machinery with meiotic recombination induced by Spo11p [25].
  • The Cne PRP8 intein may be a useful drug target in addressing the cryptococcal infections so prevalent in AIDS patients [19].
  • We describe the phylogenetic relationships among the four eukaryote nuclear encoded inteins (VMA, PRP8, GLT1 and CHS2) [26].

Analytical, diagnostic and therapeutic context of Inteins


  1. Production of cyclic peptides and proteins in vivo. Scott, C.P., Abel-Santos, E., Wall, M., Wahnon, D.C., Benkovic, S.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  2. Mycobacterium tuberculosis RecA intein possesses a novel ATP-dependent site-specific double-stranded DNA endonuclease activity. Guhan, N., Muniyappa, K. J. Biol. Chem. (2002) [Pubmed]
  3. Crystal structure of a mini-intein reveals a conserved catalytic module involved in side chain cyclization of asparagine during protein splicing. Ding, Y., Xu, M.Q., Ghosh, I., Chen, X., Ferrandon, S., Lesage, G., Rao, Z. J. Biol. Chem. (2003) [Pubmed]
  4. Distribution of split DnaE inteins in cyanobacteria. Caspi, J., Amitai, G., Belenkiy, O., Pietrokovski, S. Mol. Microbiol. (2003) [Pubmed]
  5. Semisynthesis of cytotoxic proteins using a modified protein splicing element. Evans, T.C., Benner, J., Xu, M.Q. Protein Sci. (1998) [Pubmed]
  6. Novel lipid modifications of secreted protein signals. Mann, R.K., Beachy, P.A. Annu. Rev. Biochem. (2004) [Pubmed]
  7. An alternative protein splicing mechanism for inteins lacking an N-terminal nucleophile. Southworth, M.W., Benner, J., Perler, F.B. EMBO J. (2000) [Pubmed]
  8. Protein splicing of the yeast TFP1 intervening protein sequence: a model for self-excision. Cooper, A.A., Chen, Y.J., Lindorfer, M.A., Stevens, T.H. EMBO J. (1993) [Pubmed]
  9. Intein-mediated assembly of a functional beta-glucuronidase in transgenic plants. Yang, J., Fox, G.C., Henry-Smith, T.V. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  10. Autoproteolysis in nucleoporin biogenesis. Rosenblum, J.S., Blobel, G. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  11. The in vitro ligation of bacterially expressed proteins using an intein from Methanobacterium thermoautotrophicum. Evans, T.C., Benner, J., Xu, M.Q. J. Biol. Chem. (1999) [Pubmed]
  12. Crystal structures of an intein from the split dnaE gene of Synechocystis sp. PCC6803 reveal the catalytic model without the penultimate histidine and the mechanism of zinc ion inhibition of protein splicing. Sun, P., Ye, S., Ferrandon, S., Evans, T.C., Xu, M.Q., Rao, Z. J. Mol. Biol. (2005) [Pubmed]
  13. Mycobacterium tuberculosis RecA intein, a LAGLIDADG homing endonuclease, displays Mn(2+) and DNA-dependent ATPase activity. Guhan, N., Muniyappa, K. Nucleic Acids Res. (2003) [Pubmed]
  14. Introns and intein coding sequence in the ribonucleotide reductase genes of Bacillus subtilis temperate bacteriophage SPbeta. Lazarevic, V., Soldo, B., Düsterhöft, A., Hilbert, H., Mauël, C., Karamata, D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  15. Protein splicing of inteins with atypical glutamine and aspartate C-terminal residues. Amitai, G., Dassa, B., Pietrokovski, S. J. Biol. Chem. (2004) [Pubmed]
  16. Inteins of Thermococcus fumicolans DNA polymerase are endonucleases with distinct enzymatic behaviors. Saves, I., Ozanne, V., Dietrich, J., Masson, J.M. J. Biol. Chem. (2000) [Pubmed]
  17. Split dnaE genes encoding multiple novel inteins in Trichodesmium erythraeum. Liu, X.Q., Yang, J. J. Biol. Chem. (2003) [Pubmed]
  18. Conditional protein splicing: a new tool to control protein structure and function in vitro and in vivo. Mootz, H.D., Blum, E.S., Tyszkiewicz, A.B., Muir, T.W. J. Am. Chem. Soc. (2003) [Pubmed]
  19. A nuclear-encoded intein in the fungal pathogen Cryptococcus neoformans. Butler, M.I., Goodwin, T.J., Poulter, R.T. Yeast (2001) [Pubmed]
  20. Crystal structure of GyrA intein from Mycobacterium xenopi reveals structural basis of protein splicing. Klabunde, T., Sharma, S., Telenti, A., Jacobs, W.R., Sacchettini, J.C. Nat. Struct. Biol. (1998) [Pubmed]
  21. A proposed mechanism for the self-splicing of proteins. Clarke, N.D. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  22. Protein splicing in the absence of an intein penultimate histidine. Chen, L., Benner, J., Perler, F.B. J. Biol. Chem. (2000) [Pubmed]
  23. Reversible inhibition of protein splicing by zinc ion. Mills, K.V., Paulus, H. J. Biol. Chem. (2001) [Pubmed]
  24. Targeting a truncated Ho-endonuclease of yeast to novel DNA sites with foreign zinc fingers. Nahon, E., Raveh, D. Nucleic Acids Res. (1998) [Pubmed]
  25. VDE-initiated intein homing in Saccharomyces cerevisiae proceeds in a meiotic recombination-like manner. Fukuda, T., Nogami, S., Ohya, Y. Genes Cells (2003) [Pubmed]
  26. Two new fungal inteins. Butler, M.I., Goodwin, T.J., Poulter, R.T. Yeast (2005) [Pubmed]
  27. Regulation of protein activity with small-molecule-controlled inteins. Skretas, G., Wood, D.W. Protein Sci. (2005) [Pubmed]
  28. A novel form of the plasminogen activator inhibitor created by cysteine mutations extends its half-life: relevance to cancer and angiogenesis. Chorostowska-Wynimko, J., Swiercz, R., Skrzypczak-Jankun, E., Wojtowicz, A., Selman, S.H., Jankun, J. Mol. Cancer Ther. (2003) [Pubmed]
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