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The Degradome database: mammalian proteases and diseases of proteolysis.

Nucleic acids research | Jan 16, 2009

The degradome is defined as the complete set of proteases present in an organism. The recent availability of whole genomic sequences from multiple organisms has led us to predict the contents of the degradomes of several mammalian species. To ensure the fidelity of these predictions, our methods have included manual curation of individual sequences and, when necessary, direct cloning and sequencing experiments. The results of these studies in human, chimpanzee, mouse and rat have been incorporated into the Degradome database, which can be accessed through a web interface at http://degradome.uniovi.es. The annotations about each individual protease can be retrieved by browsing catalytic classes and families or by searching specific terms. This web site also provides detailed information about genetic diseases of proteolysis, a growing field of great importance for multiple users. Finally, the user can find additional information about protease structures, protease inhibitors, ancillary domains of proteases and differences between mammalian degradomes.

Pubmed ID: 18776217 RIS Download

Mesh terms: Animals | Databases, Protein | Genetic Diseases, Inborn | Humans | Mice | Mutation | Pan troglodytes | Peptide Hydrolases | Proteome | Rats

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Mammalian Degradome Database

A database of human, chimpanzee, mouse, and rat proteases and protease inhibitors, as well as as the growing number of hereditary diseases caused by mutations in protease genes. Analysis of the human and mouse genomes has allowed us to annotate 581 human, 580 chimpanzee, 667 mouse, and 655 rat protease genes. Proteases are classified in five different classes according to their mechanism of catalysis. Proteases are a diverse and important group of enzymes representing >2% of the human, chimpanzee, mouse and rat genomes. This group of enzymes is implicated in numerous physiological processes. The importance of proteases is illustrated by the existence of 99 different hereditary diseases due to mutations in protease genes. Furthermore, proteases have been implicated in multiple human pathologies, including vascular diseases, rheumatoid arthritis, neurodegenerative processes, and cancer. During the last ten years, our laboratory has identified and characterized more than 60 human protease genes. Due to the importance of proteolytic enzymes in human physiology and pathology, we have recently introduced the concept of Degradome, as the complete repertoire of proteases expressed by a tissue or organism. Thanks to the recent completion of the human, chimpanzee, mouse, and rat genome sequencing projects, we were able to analyze and compare for the first time the complete protease repertoire in those mammalian organisms, as well as the complement of protease inhibitor genes. This webpage also contains the Supplementary Material of Human and mouse proteases: a comparative genomic approach Nat Rev Genet (2003) 4: 544-558, Genome sequence of the brown Norway rat yields insights into mammalian evolution Nature (2004) 428: 493-521, A genomic analysis of rat proteases and protease inhibitors Genome Res. (2004) 14: 609-622, and Comparative genomic analysis of human and chimpanzee proteases Genomics (2005) 86: 638-647.

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Human Hereditary Diseases of Proteolysis

This resource has cataloged a total of 80 human hereditary diseases caused by mutations in protease-coding genes, which implies that more than 10% of the human protease genes are involved in human pathologies. They are classified in three groups: loss of function, gain of function, and an heterogeneous group including non-protease homologs (np), putative proteases, and hedgehog proteins with only autoprocessing activity. Type of inheritance is indicated by R (recessive) or D (dominant).

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Ancillary Domains Associated With Human and Mouse Proteases

Domains found in human and mouse proteases colour-coded according to the catalytic class in which they appear. Some of them appear in more than one catalytic group, and two-colours are used. Yellow, aspartyl proteases; blue, cysteine proteases; green, metalloproteases; and red, serine proteases.

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