Post-translational modification (PTM) is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis for many proteins.
A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated in proteins. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching to it other biochemical functional groups such as acetate, phosphate, various lipids and carbohydrates, by changing the chemical nature of an amino acid (e.g. citrullination) or by making structural changes, like the formation of disulfide bridges.
Also, enzymes may remove amino acids from the amino end of the protein, or cut the peptide chain in the middle. For instance, the peptide hormone insulin is cut twice after disulfide bonds are formed, and a propeptide is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds.
Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.
PTMs involving addition of functional groups
PTMs involving addition include:
- acetylation, the addition of an acetyl group, usually at the N-terminus of the protein
- alkylation, the addition of an alkyl group (e.g. methyl, ethyl)
- methylation the addition of a methyl group, usually at lysine or arginine residues. (This is a type of alkylation.)
- amidation at C-terminus
- biotinylation, acylation of conserved lysine residues with a biotin appendage
- gamma-carboxylation dependent on Vitamin K
- glutamylation, covalent linkage of glutamic acid residues to tubulin and some other proteins. (See tubulin polyglutamylase)
- glycosylation, the addition of a glycosyl group to either asparagine, hydroxylysine, serine, or threonine, resulting in a glycoprotein. Distinct from glycation, which is regarded as a nonenzymatic attachment of sugars.
- glycylation, covalent linkage of one to more than 40 glycine residues to the tubulin C-terminal tail
- heme moiety may be covalently attached
- iodination (e.g. of thyroid hormones)
- isoprenylation, the addition of an isoprenoid group (e.g. farnesol and geranylgeraniol)
- lipoylation, attachment of a lipoate functionality
- nucleotides or derivatives thereof may be covalently attached
- flavin attachment
- phosphatidylinositol may be covalently attached
- phosphopantetheinylation, the addition of a 4'-phosphopantetheinyl moiety from coenzyme A, as in fatty acid, polyketide, non-ribosomal peptide and leucine biosynthesis
- phosphorylation, the addition of a phosphate group, usually to serine, tyrosine, threonine or histidine
- pyroglutamate formation
- racemization of proline by prolyl isomerase
- tRNA-mediation addition of amino acids such as arginylation
- sulfation, the addition of a sulfate group to a tyrosine.
- Selenoylation (co-translational incorporation of selenium in selenoproteins)
PTMs involving addition of other proteins or peptides
- ISGylation, the covalent linkage to the ISG15 protein (Interferon-Stimulated Gene 15)
- SUMOylation, the covalent linkage to the SUMO protein (Small Ubiquitin-related MOdifier)
- ubiquitination, the covalent linkage to the protein ubiquitin.
PTMs involving changing the chemical nature of amino acids
PTMs involving structural changes
- ^ Gramatikoff K. in Abgent Catalog (2004-5) p.263
- ^ Walker, 2001 
- ^ 
- ^ Malakhova, Oxana A.; Yan, Ming; Malakhov, Michael P.; Yuan, Youzhong; Ritchie, Kenneth J.; Kim, Keun Il; Peterson, Luke F.; Shuai, Ke; and Dong-Er Zhang. (2003). Protein ISGylation modulates the JAK-STAT signaling pathway. Genes & Development 17 (4), 455-460.
- ^ Van G. Wilson (Ed.) (2004). Sumoylation: Molecular Biology and Biochemistry. Horizon Bioscience. ISBN 0-9545232-8-8.