Posttranslational Modification and Human Disorders


Most proteins undergo modification involving specific cleavage of the polypeptide backbone and/or changes to the side chains. Some of these modifications result in disease or disorder; others may be used diagnostically.

Keywords: posttranslational; processing; amyloid; glycosylation; toxins

Figure 1.

Three major types of posttranslational modification. (1) Cleavage of the backbone by specific proteases (P). (2) Modifications of the side chains by the addition of a group (A) catalyzed by transferases and other enzymes (T); some of these are reversible by various hydrolases (H). (3) Nonenzymic modifications by reactive molecules, ions and radicals.

Figure 2.

Metabolism of amyloid precursor protein (APP). The location of the Aβ fragment is highlighted. (a) Action of α and γ secretases. (b) Action of β and γ secretases producing Aβ (the amyloidogenic pathway).



Dennis JW, Granovsky M and Warren CE (1999) Glycoprotein glycosylation and cancer progression. Biochimica et Biophysica Acta 1473: 21–34.

Dobson CM (1999) Protein misfolding, evolution and disease. Trends in Biochemical Sciences 24: 329–332.

Durand G and Seta N (2000) Protein glycosylation and diseases: blood and urinary oligosaccharides as markers for diagnosis and therapeutic monitoring. Clinical Chemistry 46: 795–805.

Galetti P, Ingrosso D, Manna C, Clemente G and Zappia V (1995) Protein damage and methylation‐mediated repair in the erythrocyte. Biochemical Journal 305: 315–325.

Hardy J (1997) Amyloid, the presenilins and Alzheimer's disease. Trends in Neurological Sciences 20: 154–159.

Henschen AH (1993) Human fibrinogen – structural variants and functional sites. Thrombosis and Haemostasis 70: 42–47.

Montecucco C and Schiavo G (1993) Tetanus and botulism neurotoxins: a new group of zinc proteases. Trends in Biochemical Sciences 18: 324–327.

Nalivaeva NN and Turner AJ (2001) Post‐translational modification of proteins: acetylcholinesterase as a model system. Proteomics 1: 735–747.

Pallen MJ, Lam AC, Loman NJ and McBride A (2001) An abundance of bacterial ADP‐ribosyltransferases – implications for the origins of exotoxins and their human homologues. Trends in Microbiology 9: 302–307.

Ulrich P and Cerami A (2001) Protein glycation, diabetes and aging. Recent Progress in Hormone Research 56: 1–21.

Further Reading

Han K‐K and Martinage A (1992) Post‐translational chemical modification(s) of proteins. International Journal of Biochemistry 24: 19–28.

Harding JH (1985) Nonenzymatic covalent posttranslational modification of proteins in vivo. Advances in Protein Chemistry 37: 248–334.

Krishna RG and Wold F (1993) Post‐translational modification of proteins. Advances in Enzymology 67: 265–298.

Meyer MJ and Ross WE (1996) Protein adduct biomarkers: state of the art. Environmental Health Perspectives 104(supplement 5): 879–882.

Parekh RB and Rohlff C (1997) Post‐translational modification of proteins and the discovery of new medicine. Current Opinion in Biotechnology 8: 718–723.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Wisdom, G Brian(Jan 2006) Posttranslational Modification and Human Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005498]