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Clustering of sequences

Pairwise sequence comparison of the core phosphatase sequences shows that the sequences cluster into four distinct groups. The sequences within each group show greater similarity to each other than they do to other phosphatase sequences. The groupings are: PP1-like sequences, PP2A-like and PP2B-like. Human PP5 ( A.E. McPartlin, H.M. Barker and P.T.W. Cohen, in preparation) and S.cerevisiae PPT [36] form a fourth distinct group which shows least similarity to all other phosphatase sequences in this region. Table 1 lists the range of sequence identity seen within and between the classes in the phosphatase domain shown in Figure 1. The three major groups are consistent with known physico-chemical properties of these phosphatases. In addition PP2B-like structures all possess long C-terminal extensions that bind and calmodulin, whilst all PP2A-like and most PP1-like structures have no long N or C-terminal extensions. The exceptions in the PP1-like group are S.cerevisiae PPQ [37] PPZ1 and PPZ2 [38] which have long serine rich N-terminal extensions. PP5 and PPT possess long N-terminal extensions with a repeat structure. The clustering performed here is sufficient to provide a guide for structure prediction. However, more detailed considerations of the evolutionary relationships between the full-length serine/threonine phosphatases will be presented elsewhere.

Figure 1 illustrates a multiple alignment of the common core of the eukaryotic phosphatase sequences; the four groupings are delineated by horizontal lines. The boxing and shading reflects conservation of physico chemical properties within each group and across the entire set of sequences (see legend for details).


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