For publication of results, please cite the following article:
|
GPS-CCD: A Novel computational program for the prediction of calpain cleavage sites
Zexian Liu , Jun Cao, xinjiao Gao, Qian Ma, Jian ren And Yu Xue . PLoS ONE , 2011 ,(Accepted
) [Abstract] [Full Text] [PDF] |
Calpains constitute an important family of
Ca 2 +-dependent cysteine proteases, which contain a nucleus ophilic Cysteine
In the specified tically active site (gollEt al
, 2003
; FrancoEt al
, 2005
;
ZatzEt al
, 2005
; LiuEt al
, 2008
). Calpains are widely expressed in mammalians and conserved processing SS eukaryotes (FutaiEt al
, 2001
; CroallEt al
, 2007
).
For instance, in budding yeast, at least one Calpain-like protease,
Rim13/cpl1, has been identified, although its functions are still
Elusive (HayashiEt al
, 2001
).
In humans, there are over 14 distinct members of the Calpain
Superfamily, some of which are tissue specific. Calpain 1 (μ-Calpain,
Micromolar Ca 2 +-requiring) and Calpain 2 (M-Calpain, millimolar
Ca 2 +-requiring) are ubiquitously expressed and well characterized
Isoforms (HuangEt al
, 2005
). Through spatial and temporal cleavage of a variety of substrates to change their conformation, function and stability (gladingEt al
, 2002
),
Ca 2 +-activated calpains play an important role in numerous biological
Processes, including the regulation of gene expression, signal
Transduction, cell death/apoptosis, remodeling Cytoskeletal attachments
During cell fusion/motility and cell cycle progression (SquierEt al
, 1999
; TanEt al
, 2006
; YousefiEt al
, 2006
). Moreover, Calpain aberrancies are frequently implicated in a variety of diseases and cancers (ArringtonEt al
, 2006
; WilliamsEt al
, 2008
).
Although implements studies have tried to dissect the regulatory roles and
Molecular Mechanic ISMs of Calpain-dependent cleavage, in fact our
Understanding of calpain is still fragmentary.
In this work, we collected368
Experimentally verified Calpain cleavage sites in130
Proteins. With a previusly developed algorithmGPS
(Group-based prediction system) (XueEt al
, 2008
),
We developed a novel software package of GPS-CCD (Calpain cleavage
Detector) for the prediction of calpain cleavage sites.
Leave-one-out validation and 4-, 6-, 8-, 10-fold cross-Validations were
Specified med to evaluate the performance of the prediction system.
Comparison,GPS 2.0
Algorithm was employed for its outstanding prediction performance, with an accuracy89.98%
, Sensiti.pdf60.87%
And specificity90.07%
.
Furthermore, there are using proteins experimentally identified
Calpain substrates for which the exact cleavage sites have not been
Verified, And we collected 196 such proteins from PubMed. As
Application, we predicted potential Calpain cleavage sites for these
Targets. These prediction results might be a useful resource
Further Experimental Investigation. Finally, the online service and
Local packagesGPS-CCD
1.0 were implemented in Java 1.5 (j2se 5.0) and are freely available for academic researchers at: http://ccd.biocuckoo.org/
.
GPS-CCD
1.0 user interface