Phospho-Serine/Threonine binding domains

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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. All appear to be selective for some surrounding residues in the phosphopeptide, and they come from several different structural superfamilies.

The best known pSer/pThr binding domains are 14-3-3, polo box, FHA, FF, BRCT, WW, WD40, and MH2 families (culled mostly from the very useful Pawson lab website. These are found in about 300 human proteins (we found 365, in a recent HMM search of the refseq database).


The best characterized pSer-binding domain. Two structural relatives, the MH2 and IRF-3 domains are also likely pSer-binding domains (see below)


The MAD Homology 2 domain 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).


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.


Found in several transcription and splicing factors, and frequently in WW-domain proteins. Two FF proteins - CA150 and FBP11 - bind the pSer-rich tail of RNA polymerase


9 members in human, largely known as pSer/pThr motif-binding domains


Domain found in many DNA damage repair proteins, a pair of BRCT domains (e.g. in BRCA1 or RAD9) can bind pSer peptides.


A widespread protein-interaction domain, of which some members (bTRCP and CDC4) bind specifically to pSer or pThr motifs. Many or most are probably not phospho-specific

Polo Box

This domain is found only in the Polo kinase family (4 genes in human) and is conserved throughout most eukaryotes.


Various members bind to either pSer/pThr containing peptides or proline-rich peptides.