The Degradome database: expanding roles of mammalian proteases in life and disease

Abstract

Since the definition of the degradome as the complete repertoire of proteases in a given organism, the combined effort of numerous laboratories has greatly expanded our knowledge of its roles in biology and pathology. Once the genomic sequences of several important model organisms were made available, we presented the Degradome database containing the curated sets of known protease genes in human, chimpanzee, mouse and rat. Here, we describe the updated Degradome database, featuring 81 new protease genes and 7 new protease families. Notably, in this short time span, the number of known hereditary diseases caused by mutations in protease genes has increased from 77 to 119. This increase reflects the growing interest on the roles of the degradome in multiple diseases, including cancer and ageing. Finally, we have leveraged the widespread adoption of new webtools to provide interactive graphic views that show information about proteases in the global context of the degradome. The Degradome database can be accessed through its web interface at http://degradome.uniovi.es.

Figure 1.

New annotations of proteases and degradomopathies. The number of proteases and degradomopathies annotated in each catalytic class is represented at the time of creation of the database (2009) and at the current version (2015).

Figure 2.

New features of the Degradome database. (A) Individual annotations of aspartyl proteases. The first column contains the name of the family, with a hyperlink to a web page where the user can find related selected publications and structures. The second column contains the name of each protease, with a hyperlink which opens a popup table with further general information—in this example, presenilin 1. Pseudogenes are shown over a pink background. Proteases absent in a species are shown as empty grey cells. (B) Interactive representation of the degradomes of (from outer to inner ticks) human, chimpanzee, mouse and rat. Protease families are limited with black and white boxes. Catalytic classes are shown as background colored arcs. Proteases which have been pseudogenized are depicted as blue ticks, and proteases absent in an organism are shown as grey ticks. Human collagenase-3 is highlighted to show the interactivity of the ticks.