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Posttranslational modification (PTM) is a step in protein biosynthesis. Proteins are created by ribosomes translating mRNA into polypeptide chains. These polypeptide chains undergo PTM, (such as folding, cutting and other processes), before becoming the mature protein product.

Posttranslational modification of insulin. At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the endoplasmic reticulum, where it is cut, folded and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the golgi apparatus, where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.

A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated to become a protein. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching it to other biochemical functional groups (such as acetate, phosphate, various lipids and carbohydrates), changing the chemical nature of an amino acid (e.g. citrullination), or making structural changes (e.g. 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. Also, most nascent polypeptides start with the amino acid methionine because the "start" codon on mRNA also codes for this amino acid. This amino acid is usually taken off during post-translational modification.

Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.

Post-translational modification of proteins is detected by mass spectrometry or Eastern blotting.

PTMs involving addition of functional groups


The genetic code diagram[1] showing the amino acid residues as target of modification.

PTMs involving addition by an enzyme in vivo

PTMs involving addition of hydrophobic groups for membrane localization

  • myristoylation, attachment of myristate, a C14 saturated acid
  • palmitoylation, attachment of palmitate, a C16 saturated acid
  • isoprenylation or prenylation, the addition of an isoprenoid group (e.g. farnesol and geranylgeraniol)
    • farnesylation
    • geranylgeranylation
  • glypiation, glycosylphosphatidylinositol (GPI) anchor formation via an amide bond to C-terminal tail

PTMs involving addition of cofactors for enhanced enzymatic activity

  • lipoylation, attachment of a lipoate (C8) functional group
  • flavin moiety (FMN or FAD) may be covalently attached
  • heme C attachment via thioether bonds with cysteins
  • phosphopantetheinylation, the addition of a 4'-phosphopantetheinyl moiety from coenzyme A, as in fatty acid, polyketide, non-ribosomal peptide and leucine biosynthesis
  • retinylidene Schiff base formation

PTMs involving unique modifications of translation factors

  • diphthamide formation (on a histidine found in eEF2)
  • ethanolamine phosphoglycerol attachment (on glutamte found in eEF1α)[2]
  • hypusine formation (on conserved lysine of eIF5A (eukaryotic) and aIF5A (archeal))

PTMs involving addition of smaller chemical groups

  • acylation, e.g. O-acylation (esters), N-acylation (amides), S-acylation (thioesters)
  • alkylation, the addition of an alkyl group, e.g. methyl, ethyl
  • amide bond formation
    • amidation at C-terminus
    • amino acid addition
      • arginylation, a tRNA-mediation addition
      • polyglutamylation, covalent linkage of glutamic acid residues to the N-terminus of tubulin and some other proteins.[7] (See tubulin polyglutamylase)
      • polyglycylation, covalent linkage of one to more than 40 glycine residues to the tubulin C-terminal tail
  • butyrylation
  • gamma-carboxylation dependent on Vitamin K[8]
  • glycosylation, the addition of a glycosyl group to either arginine, asparagine, cysteine, hydroxylysine, serine, threonine, tyrosine, or tryptophan resulting in a glycoprotein. Distinct from glycation, which is regarded as a nonenzymatic attachment of sugars.
    • polysialylation, addition of polysialic acid, PSA, to NCAM
  • malonylation
  • hydroxylation
  • iodination (e.g. of thyroglobulin)
  • nucleotide addition such as ADP-ribosylation
  • oxidation
  • phosphate ester (O-linked) or phosphoramidate (N-linked) formation
  • propionylation
  • pyroglutamate formation
  • S-glutathionylation
  • S-nitrosylation
  • succinylation addition of a succinyl group to lysine
  • sulfation, the addition of a sulfate group to a tyrosine.
  • selenoylation (co-translational incorporation of selenium in selenoproteins)

PTMs involving non-enzymatic additions in vivo

  • glycation, the addition of a sugar molecule to a protein without the controlling action of an enzyme.

PTMs involving non-enzymatic additions in vitro

  • biotinylation, acylation of conserved lysine residues with a biotin appendage
  • pegylation

PTMs involving addition of other proteins or peptides

  • ISGylation, the covalent linkage to the ISG15 protein (Interferon-Stimulated Gene 15)[9]
  • SUMOylation, the covalent linkage to the SUMO protein (Small Ubiquitin-related MOdifier)[10]
  • ubiquitination, the covalent linkage to the protein ubiquitin.
  • Neddylation, the covalent linkage to Nedd
  • Pupylation, the covalent linkage to the Prokaryotic ubiquitin-like protein

PTMs involving changing the chemical nature of amino acids

PTMs involving structural changes

  • disulfide bridges, the covalent linkage of two cysteine amino acids
  • proteolytic cleavage, cleavage of a protein at a peptide bond
  • racemization of proline by prolyl isomerase

Post-translational modification statistics

Recently, statistics of each post-translational modification experimentally and putatively detected have been compiled using proteome-wide information from the Swiss-Prot database.[13] These statistics can be found at

Case examples

  • Cleavage and formation of disulfide bridges during the production of insulin
  • PTM of histones as regulation of transcription: RNA polymerase control by chromatin structure
  • PTM of RNA polymerase II as regulation of transcription
  • Cleavage of polypeptide chains as crucial for lectin specificity

External links


  1. Gramatikoff K. in Abgent Catalog (2004-5) p.263
  2. Whiteheart SW, Shenbagamurthi P, Chen L, et al. (1989). Murine elongation factor 1 alpha (EF-1 alpha) is posttranslationally modified by novel amide-linked ethanolamine-phosphoglycerol moieties. Addition of ethanolamine-phosphoglycerol to specific glutamic acid residues on EF-1 alpha.. J. Biol. Chem. 264 (24): 14334–41.
  3. Polevoda B, Sherman F (2003). N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins. J Mol Biol 325 (4): 595–622.
  4. Yang XJ, Seto E (2008). Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell 31 (4): 449–61.
  5. Bártová E, Krejcí J, Harnicarová A, Galiová G, Kozubek S (2008). Histone modifications and nuclear architecture: a review. J Histochem Cytochem 56 (8): 711–21.
  6. Glozak MA, Sengupta N, Zhang X, Seto E (2005). Acetylation and deacetylation of non-histone proteins. Gene 363: 15–23.
  7. Eddé B, Rossier J, Le Caer JP, Desbruyères E, Gros F, Denoulet P (1990). Posttranslational glutamylation of alpha-tubulin. Science 247 (4938): 83–5.
  8. Walker CS, Shetty RP, Clark K, et al. (2001). On a potential global role for vitamin K-dependent gamma-carboxylation in animal systems. Animals can experience subvaginalhemototitis as a result of this linkage. Evidence for a gamma-glutamyl carboxylase in Drosophila. J. Biol. Chem. 276 (11): 7769–74.
  9. 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): 455–60.
  10. Van G. Wilson (Ed.) (2004). Sumoylation: Molecular Biology and Biochemistry. Horizon Bioscience. ISBN 0-9545232-8-8.
  11. Brennan DF, Barford D (2009). Eliminylation: a post-translational modification catalyzed by phosphothreonine lyases. Trends in Biochemical Sciences 34 (3): 108–114.
  12. Mydel P, et al. (2010). Carbamylation-dependent activation of T cells: a novel mechanism in the pathogenesis of autoimmune arthritis.. Journal of Immunology 184 (12): 6882–6890.
  13. Khoury, George A.; Baliban, Richard C.; and Christodoulos A. Floudas (2011). Proteome-wide post-translational modification statistics: frequency analysis and curation of the swiss-prot database. Scientific Reports 1 (90).

Protein primary structure and posttranslational modifications
General: Protein biosynthesis | Peptide bond | Proteolysis | Racemization | N-O acyl shift
N-terminus: Acetylation | Formylation | Myristoylation | Pyroglutamate | methylation | glycation | myristoylation (Gly) | carbamylation
C-terminus: Amidation | Glycosyl phosphatidylinositol (GPI) | O-methylation | glypiation | ubiquitination | sumoylation
Lysine: Methylation | Acetylation | Acylation | Hydroxylation | Ubiquitination | SUMOylation | Desmosine | deamination and oxidation to aldehyde| O-glycosylation | imine formation | glycation | carbamylation
Cysteine: Disulfide bond | Prenylation | Palmitoylation
Serine/Threonine: Phosphorylation | Glycosylation
Tyrosine: Phosphorylation | Sulfation | porphyrin ring linkage | flavin linkage | GFP prosthetic group (Thr-Tyr-Gly sequence) formation | Lysine tyrosine quinone (LTQ) formation | Topaquinone (TPQ) formation
Asparagine: Deamidation | Glycosylation
Aspartate: Succinimide formation
Glutamine: Transglutamination
Glutamate: Carboxylation | polyglutamylation | polyglycylation
Arginine: Citrullination | Methylation
Proline: Hydroxylation
←Amino acids Secondary structure→

Template:Posttranslational modification Template:Gene expression

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