Prediction of proprotein convertase cleavage sites.
Peter Duckert, Søren Brunak and Nikolaj Blom1.
Protein Engineering, Design and Selection: 17: 107-112, 2004.
1to whom correspondence should be addressed, e-mail:
Center for Biological Sequence Analysis, BioCentrum-DTU,
The Technical University of Denmark, DK-2800 Lyngby, Denmark
Many secretory proteins and peptides are synthesized as inactive precursors
that in addition to signal peptide cleavage undergo post-translational
processing to become biologically active polypeptides. Precursors are
usually cleaved at sites composed of single or paired basic amino acid
residues by members of the subtilisin/kexin-like proprotein convertase (PC)
family. In mammals, seven members have been identified, with furin being the
one first discovered and best characterized. Recently, the involvement of
furin in diseases ranging from Alzheimer's disease and cancer to anthrax and
Ebola fever has created additional focus on proprotein processing. We have
developed a method for prediction of cleavage sites for PCs based on
artificial neural networks. Two different types of neural networks have been
constructed: a furin-specific network based on experimental results derived
from the literature, and a general PC-specific network trained on data from
the Swiss-Prot protein database. The method predicts cleavage sites in
independent sequences with a sensitivity of 95% for the furin neural network
and 62% for the general PC network.