GPS-CCD: A Novel Computational Program for the Prediction of Calpain Cleavage Sites

Abstract

As one of the most essential post-translational modifications (PTMs) of proteins, proteolysis, especially calpain-mediated cleavage, plays an important role in many biological processes, including cell death/apoptosis, cytoskeletal remodeling, and the cell cycle. Experimental identification of calpain targets with bona fide cleavage sites is fundamental for dissecting the molecular mechanisms and biological roles of calpain cleavage. In contrast to time-consuming and labor-intensive experimental approaches, computational prediction of calpain cleavage sites might more cheaply and readily provide useful information for further experimental investigation. In this work, we constructed a novel software package of GPS-CCD (Calpain Cleavage Detector) for the prediction of calpain cleavage sites, with an accuracy of 89.98%, sensitivity of 60.87% and specificity of 90.07%. With this software, we annotated potential calpain cleavage sites for hundreds of calpain substrates, for which the exact cleavage sites had not been previously determined. In this regard, GPS-CCD 1.0 is considered to be a useful tool for experimentalists. The online service and local packages of GPS-CCD 1.0 were implemented in JAVA and are freely available at: http://ccd.biocuckoo.org/.

Calpains and neuronal damage in the ischemic brain: The swiss knife in synaptic injury

“…Therefore, the prediction of calpain cleavage sites is the key to understand how calpain activity modulates cellular mechanisms through substrate proteolysis. Several studies have tried to predict calpain cleavage sites by analysis of substrate primary structure (DuVerle et al, 2011;Fan et al, 2013;Liu et al, 2011;Tompa et al, 2004). However, only a limited number of these substrates are currently known (Kim et al, 2013), with the exact mechanism of substrate recognition and cleavage by calpain still to be determined.…”

Calpain inhibition rescues troponin T3 fragmentation, increases Cav1.1 , and enhances skeletal muscle force in aging sedentary mice

“…TMPP‐labeled TnT3 N‐terminal amino acids are shown in red. GPS‐CCD 1.0 (Liu et al, 2011) indicates that two of three of the TMPP‐labeled sites are calpain cleavage sites.…”

Negative Regulation of 26S Proteasome Stability via Calpain-mediated Cleavage of Rpn10 Subunit upon Mitochondrial Dysfunction in Neurons

“…Calpains do not have a strict cleavage specificity, although some preferences for particular amino acid sequences, secondary structure (disordered regions), and PEST regions were suggested (55,56). To find a putative calpain cleavage site on Rpn10, we used two computational programs (GPS-CCD -The Cuckoo Workgroup (57) and Calpain for Modulatory Proteolysis Database (CaMPDB) (58)). We determined that a predicted calpain cleavage site on human Rpn10 is Ala-360 (P1 position, indicated by bold and underline) within the following sequence: AIRNAMGSLA-SQAT.…”