A large and accurate collection of peptidase cleavages in the MEROPS database

Rawlings, Neil D.

If the substrate is a protein, it is mapped to a UniProt protein sequence database entry (26) initially by name and species. Each cleavage in the protein is mapped to a specific residue in the UniProt entry. Frequently the residue number reported in the paper refers to a position in the mature protein, and to map this to the UniProt sequence the length of any signal peptide and/or propeptide has to be added. The UniProt accession, the P1 residue number, the CRC64 checksum for the sequence and the MEROPS identifier for the peptidase are stored. In addition other information may be retained, including whether the cleavage is deemed by the authors of the source paper to be physiological or not, whether the substrate was in native conformation, the pH of the reaction, and the method used to identify the cleavage. The four residues either side of the scissile bond are also stored so that the cleavage position can be recalculated should the UniProt protein sequence change, and to provide the data for what amino acids are acceptable in the binding pockets S4-S4 0 for each peptidase. A bespoke program (in Perl) was written to add each cleavage in a protein substrate to ensure consistency; the program connects to the locally installed version of UniProt so that each cleavage position can be confirmed as the data are entered. Some data were acquired from proteomics studies. Again a bespoke program was written to parse the data from the Excel spreadsheets available as Supplementary Data to the published papers. Some cleavages were acquired from the CutDB database, but these have been manually checked against the original reference and the UniProt sequence. Once again a bespoke program was written to collect the data, translate the provided substrate Protein Identifier to a Uniprot accession, check that a cleavage event was not already present in the MEROPS collection (and add the CutDB accession number if it were), and add new cleavage events to the MEROPS collection, reporting any inconsistency between the P4-P4 0 residues and the sequence in the UniProt entry.