Posttranslational modification

Posttranslational modification (PTM) is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, 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 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.

1 PTMs involving addition of functional groups
2 PTMs involving addition of other proteins or peptides
3 PTMs involving changing the chemical nature of amino acids
4 PTMs involving structural changes
5 Post-translational modification statistics
6 Case examples
7 External links
8 References

PTMs involving addition of functional groups

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)
- acetylation, the addition of an acetyl group, either at the N-terminus ^[3] of the protein or at lysine residues.^[4] See also histone acetylation.^[5]^[6] The reverse is called deacetylation.
- formylation
alkylation, the addition of an alkyl group, e.g. methyl, ethyl
- methylation the addition of a methyl group, usually at lysine or arginine residues. The reverse is called demethylation.
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
gamma-carboxylation dependent on Vitamin K^[8]
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.
- polysialylation, addition of polysialic acid, PSA, to NCAM
- ADP-ribosylation
hydroxylation
iodination (e.g. of thyroglobulin)
oxidation
phosphate ester (O-linked) or phosphoramidate (N-linked) formation
- phosphorylation, the addition of a phosphate group, usually to serine, threonine, and tyrosine (O-linked), or histidine (N-linked)
- adenylylation, the addition of an adenylyl moiety, usually to tyrosine (O-linked), or histidine and lysine (N-linked)
pyroglutamate formation
S-glutathionylation
S-nitrosylation
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

PTMs involving changing the chemical nature of amino acids

citrullination, or deimination, the conversion of arginine to citrulline
deamidation, the conversion of glutamine to glutamic acid or asparagine to aspartic acid
eliminylation, the conversion to an alkene by beta-elimination of phosphothreonine and phosphoserine, or dehydration of threonine and serine, as well as by decarboxylation of cysteine ^[11]
carbamylation, the conversion of lysine to homocitrulline ^[12]

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