Sequence databases are growing fast, challenging existing analysis pipelines. Reducing the redundancy of sequence databases by similarity clustering improves speed and sensitivity of iterative searches. But existing tools cannot efficiently cluster databases of the size of UniProt to 50% maximum pairwise sequence identity or below. Furthermore, in metagenomics experiments typically large fractions of reads cannot be matched to any known sequence anymore because searching with sensitive but relatively slow tools (e.g. BLAST or HMMER3) through comprehensive databases such as UniProt is becoming too costly.