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. 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 degron

Degron

A degron is a specific sequence of amino acids in a protein that directs the starting place of degradation. A degron sequence can occur at either the N or C-terminal region, these are called N-Degrons or C-degrons respectively....

s, can also be found in sequence.

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

• 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

External links

• Prediction of half-life of proteins in different organisms according N-end rule