A genomic perspective on human proteases

Over 400 human proteases documented in secondary databases can already be delineated in genomic sequence. A Genome Ontology annotation of 30585 sequences in the provisional human proteome set recognises 498 proteases, i.e. 1.6%. Homology searches against finished sequence and comparisons between mouse and zebrafish are likely to increase this total. However, the data already indicate that the mechanistic class, sequence family and domain distribution of the genomic complement of proteases is unlikely to shift significantly from that already observed in the transcript data. Genomically derived novel sequences will require bioinformatic analysis and biochemical verification. The increasing availability of annotated genomic data will enable studies of splice variants, transcriptional control, polymorphisms, pseudogenes, inactive homologues and evolution. Comparative work on complete human protease families should produce a more integrated picture of their biochemistry and physiology. Genomic data will also lead to the identification of new protease involvement in disease processes and their evaluation as drug targets.