: CLUSS is an algorithm proposed for clustering both alignable and non-alignable protein sequences. However, CLUSS tends to be ineffective on protein datasets that include a large number of biochemical activities. To overcome this difficulty, we propose in this paper a new algorithm, named CLUSS2 that scales better with the increase of the number of biochemical activities. CLUSS2 differs from CLUSS in many ways including protein sequences representation, conserved motifs extraction and time efficiency. Our experiments show that CLUSS2 more accurately highlights the functional characteristics of the clustered families, especially for those with a large number of biochemical activities.