Serine

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Standard codons for S : AGC AGT TCA TCC TCG TCT

Substitution preferences:
All protein types:
Favoured Ala ( 1) Asn ( 1) Thr ( 1)
Neutral Glu ( 0) Lys ( 0) Gly ( 0) Gln ( 0) Asp ( 0)
Disfavoured Arg (-1) Met (-1) His (-1) Pro (-1) Cys (-1) Leu (-2) Val (-2) Phe (-2)
Tyr (-2) Ile (-2) Trp (-3)

Intracellular proteins:
Favoured
Neutral Cys ( 0) Asp ( 0) Glu ( 0) Lys ( 0) Gly ( 0) His ( 0) Asn ( 0) Pro ( 0)
Gln ( 0) Arg ( 0) Ala ( 0) Thr ( 0)
Disfavoured Val (-1) Tyr (-1) Met (-1) Phe (-2) Trp (-2) Ile (-2) Leu (-2)

Extracellular proteins:
Favoured Thr ( 1)
Neutral Pro ( 0) Asp ( 0) Glu ( 0) Asn ( 0) Gly ( 0) His ( 0) Lys ( 0) Arg ( 0)
Ala ( 0) Gln ( 0)
Disfavoured Ile (-1) Met (-1) Leu (-1) Val (-1) Trp (-1) Tyr (-1) Phe (-2) Cys (-5)

Membrane proteins:
Favoured Asn ( 2) Thr ( 2) Ala ( 2) Cys ( 1) Gly ( 1)
Neutral Glu ( 0) Tyr ( 0) Asp ( 0)
Disfavoured Pro (-1) Gln (-1) Phe (-1) Lys (-1) Arg (-1) Val (-1) Ile (-1) His (-2)
Leu (-2) Met (-2) Trp (-3)

Substitutions: As Serine is generally considered a slightly polar polar, amino acid, though it is fairly neutral with regard to mutations, though generally it subsitutes with other polar or small amino acids, in particular Threonine which differs only in that it has a methyl group in place of a hydrogen group found in Serine.

Role in structure: Being a fairly indifferent amino acid, Serine can reside both within the interior of a protein, or on the protein surface. Its small size means that it is relatively common within tight turns on the protein surface, where it is possible for the Serine side-chain hydroxyl oxygen to form a hydrogen bond with the protein backbone, effectively mimicking Proline.

Role in function: Serines are quite common in protein functional centres. The hydroxyl group is fairly reactive, being able to form hydrogen bonds with a variety of polar substrates.

Perhaps the best known role for Serine in protein active sites is found in the classical Asp-His-Ser catalytic triad found in many hydrolases (e.g. proteases, lipases, etc.). Here, a Serine, aided by a Histidine and an Aspartate acts as a nucleophile to hydrolyse (effectively cut) other molecules.

This three-dimensional `motif' is found in many non-homologous (i.e. un-related) proteins, and is a classic example of molecular convergent evolution. Note that in this context, it is rare for Serine to exchange with Threonine, but in some cases, the reactive serine can be replaced by Cysteine, which can perform a similar role.

A common role for Serines (and Threonines and Tyrosines) within intracellular proteins is phosphorylation. Protein kinases frequently attach phosphates to Serines in order to fascilitate the signal transduction process. Note that in this context, Serine can often be replaced by Threonine, but is unlikely to be replaced by Tyrosine, as the enzymes that catalyse the reactions (i.e. the protein kinases) are highly specific (i.e. Tyrosine kinases generally do not work on Serines/Threonines and vice versa).

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Please cite: M.J. Betts, R.B. Russell. Amino acid properties and consequences of subsitutions.
In Bioinformatics for Geneticists, M.R. Barnes, I.C. Gray eds, Wiley, 2003..