Phospho-Serine/Threonine binding domains

Several domains are known to bind selectively to pSer or pThr residues in proteins. Many of these are in domain families that are also known as protein-protein interaction domains, and so may have some or most members that are not selective to binding phospho residues.

The best known pSer/pThr binding domains are 14-3-3, polo box, FHA, FF, BRCT, WD40, and MH2 families (culled mostly from the very useful Pawson lab website. These are found in about 300 human proteins (we found 317, in a recent HMM search of the refseq database).

FHA domain

The best characterized pSer-binding domain

MH2 domain

The MAD-homology2 region found in SMADs binds phosphorylated SxxS motifs both in TGFb receptors and in each other. It is structurally related to the FHA domain (forming a Pfam Clan, and a SCOP superfamily).

IRF-3

IRFs are interferon regulated transcription factors (9 genes in human) that are activated by phosphorylation. This domain is structurally related to both MH2 and FHA and it has been proposed that is involved in oligomerization after phosphorylation by binding pSer motifs. 

FF

Named after a highly-conserved pair of Phe residues,