N-end rule

N-end rule

The N-end rule is a rule related to ubiquitination, discovered by Alexander Varshavsky in 1986. The rule, which states that the nature of the N-terminal amino acids of a protein is an important factor that governs its half-life (likelihood of being degraded), is applicable to both eukaryotic and prokaryotic organisms, but with different strength.[1] However, only rough estimations of protein half-life can be deduced from this 'rule', as N-terminal amino acid modification can lead to variability and anomalies, whilst amino acid impact can also change from organism to organism. Other degradation signals, known as degrons, can also be found in sequence.

Contents

Relationships

N-terminal residues - approximate half-life of proteins for S. cerevisiae

  • Met, Gly, Ala, Ser, Thr, Val, Pro - > 20 hrs (stabilising)
  • Ile, Glu - approx. 30 min (stabilising)
  • Tyr, Gln - approx. 10 min (destabilisiing)
  • Leu, Phe, Asp, Lys - approx. 3 min (destabilising)
  • Arg - approx. 2 min (destabilising)

"N"-terminal residues - approximate half-life of proteins in mammalian systems [2]

  • Val -> 100h
  • Met, Gly -> 30h
  • Pro - > 20h
  • Ile -> 20h
  • Thr -> 7.2h
  • Leu -> 5.5h
  • Ala -> 4.4h
  • His -> 3.5h
  • Trp -> 2.8h
  • Tyr -> 2.8h
  • Ser -> 1.9h
  • Asn -> 1.4h
  • Lys -> 1.3h
  • Cys -> 1.2h
  • Asp -> 1.1h
  • Phe -> 1.1h
  • Glu -> 1.0h
  • Arg -> 1.0h
  • Gln -> 0.8h


See also

References

  1. ^ Alexander, Varshavsky (1997). "The N-end rule pathway of protein degradation". Genes to Cells 2 (1): 13–28. doi:10.1046/j.1365-2443.1997.1020301.x. PMID 9112437. 
  2. ^ David K. Gonda et al. (1989). "Universality and Structure of the N-end Rule.". Journal of Biological Chemistry 264 (28): 16700–16712. PMID 2506181. 

External links


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