Open AccessCaspase Cleavage Sites in the Human Proteome: CaspDB, a Database of Predicted Substrates
Author(s) -
Sonu Kumar,
Bram J. van Raam,
Guy S. Salvesen,
Piotr Cieplak
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0110539
Subject(s) - caspase , uniprot , proteome , biology , proteases , in silico , cleavage (geology) , computational biology , human proteome project , database , caspase 7 , proteomics , microbiology and biotechnology , bioinformatics , biochemistry , apoptosis , enzyme , programmed cell death , computer science , gene , paleontology , fracture (geology)
Caspases are enzymes belonging to a conserved family of c ysteine-dependent asp artic-specific prote ases that are involved in vital cellular processes and play a prominent role in apoptosis and inflammation. Determining all relevant protein substrates of caspases remains a challenging task. Over 1500 caspase substrates have been discovered in the human proteome according to published data and new substrates are discovered on a daily basis. To aid the discovery process we developed a caspase cleavage prediction method using the recently published curated MerCASBA database of experimentally determined caspase substrates and a Random Forest classification method. On both internal and external test sets, the ranking of predicted cleavage positions is superior to all previously developed prediction methods. The in silico predicted caspase cleavage positions in human proteins are available from a relational database: CaspDB. Our database provides information about potential cleavage sites in a verified set of all human proteins collected in Uniprot and their orthologs, allowing for tracing of cleavage motif conservation. It also provides information about the positions of disease-annotated single nucleotide polymorphisms, and posttranslational modifications that may modulate the caspase cleaving efficiency.