Home LiteratureArticle Details
PMID: 15980455 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Validation Study

GraBCas: a bioinformatics tool for score-based prediction of Caspase- and Granzyme B-cleavage sites in protein sequences.

Nucleic acids research ·Vol. 33 ·No. Web Server issue ·2005-07-01 ·Pages W208-13

Backes C, Kuentzer J, Lenhof HP, Comtesse N, Meese E

Abstract

Caspases and granzyme B are proteases that share the primary specificity to cleave at the carboxyl terminal of aspartate residues in their substrates. Both, caspases and granzyme B are enzymes that are involved in fundamental cellular processes and play a central role in apoptotic cell death. Although various targets are described, many substrates still await identification and many cleavage sites of known substrates are not identified or experimentally verified. A more comprehensive knowledge of caspase and granzyme B substrates is essential to understand the biological roles of these enzymes in more detail. The relatively high variability in cleavage site recognition sequence often complicates the identification of cleavage sites. As of yet there is no software available that allows identification of caspase and/or granzyme with cleavage sites differing from the consensus sequence. Here, we present a bioinformatics tool 'GraBCas' that provides score-based prediction of potential cleavage sites for the caspases 1-9 and granzyme B including an estimation of the fragment size. We tested GraBCas on already known substrates and showed its usefulness for protein sequence analysis. GraBCas is available at http://wwwalt.med-rz.uniklinik-saarland.de/med_fak/humangenetik/software/index.html.

MeSH Terms
Caspases/metabolism Computational Biology/methods Granzymes Internet Sequence Analysis, Protein/methods Serine Endopeptidases/metabolism Software Substrate Specificity
Chemicals
Granzymes Serine Endopeptidases Caspases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Backes Christina
Department of Human Genetics Building 60 Medical School, University of Saarland, 66421 Homburg/Saar, Germany.
Kuentzer Jan
Lenhof Hans-Peter
Comtesse Nicole
Meese Eckart
References (15)
15 references, click to expand
  1. DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis.
    Immunity. 2000 Jun;12(6):621-32 PMID: 10894162
  2. Cleavage by granzyme B is strongly predictive of autoantigen status: implications for initiation of autoimmunity.
    J Exp Med. 1999 Sep 20;190(6):815-26 PMID: 10499920
  3. Initiation of apoptosis by granzyme B requires direct cleavage of bid, but not direct granzyme B-mediated caspase activation.
    J Exp Med. 2000 Nov 20;192(10):1403-14 PMID: 11085743
  4. Caspases: more than just killers?
    Trends Immunol. 2001 Jan;22(1):31-4 PMID: 11286689
  5. Direct cleavage of the human DNA fragmentation factor-45 by granzyme B induces caspase-activated DNase release and DNA fragmentation.
    EMBO J. 2001 Jun 15;20(12):3101-13 PMID: 11406587
  6. Apoptosis-independent functions of killer caspases.
    Curr Opin Cell Biol. 2002 Dec;14(6):721-6 PMID: 12473345
  7. Many cuts to ruin: a comprehensive update of caspase substrates.
    Cell Death Differ. 2003 Jan;10(1):76-100 PMID: 12655297
  8. Toward computer-based cleavage site prediction of cysteine endopeptidases.
    Biol Chem. 2003 Jun;384(6):899-909 PMID: 12887057
  9. Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells.
    Cell. 1994 Mar 25;76(6):977-87 PMID: 8137431
  10. Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B.
    Nature. 1995 Oct 5;377(6548):446-8 PMID: 7566124
  11. A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis.
    J Biol Chem. 1997 Jul 18;272(29):17907-11 PMID: 9218414
  12. Granzyme B directly and efficiently cleaves several downstream caspase substrates: implications for CTL-induced apoptosis.
    Immunity. 1998 Apr;8(4):451-60 PMID: 9586635
  13. Definition and redesign of the extended substrate specificity of granzyme B.
    J Biol Chem. 1998 Oct 16;273(42):27364-73 PMID: 9765264
  14. Purification and catalytic properties of human caspase family members.
    Cell Death Differ. 1999 Apr;6(4):362-9 PMID: 10381624
  15. Internally quenched fluorescent peptide substrates disclose the subsite preferences of human caspases 1, 3, 6, 7 and 8.
    Biochem J. 2000 Sep 1;350 Pt 2:563-8 PMID: 10947972
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
Published
2005-07-01
Pages
W208-13
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1160194
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]