The issue of clustering proteins into homologous families has attracted considerable attention by researchers. On one side, many databases of protein families have been developed by using relatively simple clustering methods and a lot of manual curation. On the other side, more elaborated clustering approaches have been used, yet with a very limited degree of success. This paper advocates an approach to clustering protein families involving the knowledge of protein functions to adjust the

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... ter of similarity scale shift. We proceed to reconstruct HPF evolutionary histories to both further narrow down the choice of the cluster solution and interpret clusters.