钙蛋白酶Calpain酶切位点预测工具 —— GPS-CCD 1.0

墨蓝 2022-05-15 05:16 260阅读 0赞

For publication of results, please cite the following article:

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   <td> <p><strong>　GPS-CCD: GPS-CCD: A novel computational program for the prediction of calpain cleavage sites</strong> <br><strong>　</strong> <a href="mailto:lzx@mail.ustc.edu.cn" rel="nofollow">Zexian Liu</a> , Jun Cao, Xinjiao Gao, Qian Ma,<a href="mailto:renjian.sysu@gmail.com" rel="nofollow">Jian Ren</a> and <a href="mailto:xueyu@mail.hust.edu.cn" rel="nofollow">Yu Xue</a> . <br><strong>　PLoS ONE</strong> , 2011, (<em><strong>Accepted</strong> </em> )</p> <p><strong>　</strong> <a href="http://ccd.biocuckoo.org/" rel="nofollow">[Abstract]</a> <a href="http://ccd.biocuckoo.org/" rel="nofollow">[Full Text]</a> <a href="http://ccd.biocuckoo.org/" rel="nofollow">[PDF]</a> </p> </td> 
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Calpains constitute an important family of the Ca2+-dependent cysteine proteases, which contain a nucleophilic cysteine in the catalytically active site ([Goll *et al* , 2003][Goll _et al_ _ 2003] ; [Franco *et al* , 2005][Franco _et al_ _ 2005] ; [Zatz *et al* , 2005][Zatz _et al_ _ 2005] ; [Liu *et al* , 2008][Liu _et al_ _ 2008] ). Calpains are widely expressed in mammalians and conserved across eukaryotes ([Futai *et al* , 2001][Futai _et al_ _ 2001] ; [Croall *et al* , 2007][Croall _et al_ _ 2007] ). For instance, in budding yeast, at least one calpain-like protease, Rim13/Cpl1, has been identified, although its functions are still elusive ([Hayashi *et al* , 2001][Hayashi _et 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 Ca2+-requiring) and Calpain 2 (m-calpain, millimolar Ca2+-requiring) are ubiquitously expressed and well characterized isoforms ([Huang *et al* , 2005][Huang _et al_ _ 2005] ). Through spatial and temporal cleavage of a variety of substrates to change their conformation, function and stability ([Glading *et al* , 2002][Glading _et al_ _ 2002] ), Ca2+-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 ([Squier *et al* , 1999][Squier _et al_ _ 1999] ; [Tan *et al* , 2006][Tan _et al_ _ 2006] ; [Yousefi *et al* , 2006][Yousefi _et al_ _ 2006] ). Moreover, calpain aberrancies are frequently implicated in a variety of diseases and cancers ([Arrington *et al* , 2006][Arrington _et al_ _ 2006] ; [Williams *et al* , 2008][Williams _et al_ _ 2008] ). Although many studies have tried to dissect the regulatory roles and molecular mechanisms of calpain-dependent cleavage, in fact our understanding of calpain is still fragmentary.

In this work, we collected **368** experimentally verified calpain cleavage sites in **130** proteins. With a previously developed algorithm of **GPS** (Group-based Prediction System)([Xue *et al* , 2008][Xue _et al_ _ 2008] ), we developed a novel software package of GPS-CCD (Calpain Cleavage Detector) for the prediction of calpain cleavage sites. The leave-one-out validation and 4-, 6-, 8-, 10-fold cross-validations were performed to evaluate the performance of the prediction system. By comparison, the **GPS 2.0**  algorithm was employed for its outstanding prediction performance, with an accuracy **89.98%** , sensitivity **60.87%** and specificity **90.07%** . Furthermore, there are many proteins experimentally identified as calpain substrates for which the exact cleavage sites have not been verified, and we collected 196 such proteins from PubMed. As an application, we predicted potential calpain cleavage sites for these targets. These prediction results might be a useful resource for further experimental investigation. Finally, the online service and local packages of **GPS-CCD** 1.0 were implemented in JAVA 1.5 (J2SE 5.0) and are freely available for academic researchers at: [http://ccd.biocuckoo.org/][http_ccd.biocuckoo.org] .

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***GPS-CCD 1.0 User Interface***

[bg06.gif]: http://ccd.biocuckoo.org/images/bg06.gif
[Goll _et al_ _ 2003]: http://www.ncbi.nlm.nih.gov/pubmed/12843408
[Franco _et al_ _ 2005]: http://www.ncbi.nlm.nih.gov/pubmed/16129881
[Zatz _et al_ _ 2005]: http://www.ncbi.nlm.nih.gov/pubmed/15944426
[Liu _et al_ _ 2008]: http://www.ncbi.nlm.nih.gov/pubmed/18398107
[Futai _et al_ _ 2001]: http://www.ncbi.nlm.nih.gov/pubmed/9928935
[Croall _et al_ _ 2007]: http://www.ncbi.nlm.nih.gov/pubmed/17608959
[Hayashi _et al_ _ 2001]: http://www.ncbi.nlm.nih.gov/pubmed/16227598
[Huang _et al_ _ 2005]: http://www.ncbi.nlm.nih.gov/pubmed/11516996
[Glading _et al_ _ 2002]: http://www.ncbi.nlm.nih.gov/pubmed/11854009
[Squier _et al_ _ 1999]: http://www.ncbi.nlm.nih.gov/pubmed/9989777
[Tan _et al_ _ 2006]: http://www.ncbi.nlm.nih.gov/pubmed/16632474
[Yousefi _et al_ _ 2006]: http://www.ncbi.nlm.nih.gov/pubmed/16998475
[Arrington _et al_ _ 2006]: http://www.ncbi.nlm.nih.gov/pubmed/16790502
[Williams _et al_ _ 2008]: http://www.ncbi.nlm.nih.gov/pubmed/18391949
[Xue _et al_ _ 2008]: http://www.ncbi.nlm.nih.gov/pubmed/18463090
[http_ccd.biocuckoo.org]: http://ccd.biocuckoo.org/
[CCD.gif]: http://ccd.biocuckoo.org/images/CCD.gif