N-end rule
The N-end rule is a rule related to ubiquitination, discovered by Alexander Varshavsky and co-workers in 1986.[1] The rule states that the N-terminal amino acid of a protein determines its half-life (likelihood of being degraded). The rule applies to both eukaryotic and prokaryotic organisms, but with different strength.[2] 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.
Relationships
N-terminal residues - approximate half-life of proteins for S. cerevisiae[1]
- Met, Gly, Ala, Ser, Thr, Val, Pro - > 20 hrs (stabilizing)
- Ile, Glu - approx. 30 min (stabilizing)
- Tyr, Gln - approx. 10 min (destabilizing)
- Leu, Phe, Asp, Lys - approx. 3 min (destabilizing)
- Arg - approx. 2 min (destabilizing)
"N"-terminal residues - approximate half-life of proteins in mammalian systems [3]
- 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
References
- ↑ 1.0 1.1 Bachmair A, Finley D, Varshavsky A. (1986). "In vivo half-life of a protein is a function of its amino-terminal residue". Science 234 (4773): 179–186. doi:10.1126/science.3018930. PMID 3018930.
- ↑ Varshavsky A. (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.
- ↑ David K. Gonda et al. (1989). "Universality and Structure of the N-end Rule.". Journal of Biological Chemistry 264 (28): 16700–16712. PMID 2506181.