PCPS: A Web Server to Predict Proteasomal Cleavage Sites

  • Marta Gomez-Perosanz
  • Alvaro Ras-Carmona
  • Pedro A. RecheEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 2131)


The proteasome complex is mainly responsible for proteolytic degradation of cytosolic proteins, generating the C-terminus of MHC I-restricted peptide ligands and CD8 T cell epitopes. Therefore, prediction of proteasomal cleavage sites is relevant for anticipating CD8 T-cell epitopes. There are two different proteasomes, the constitutive proteasome, expressed in all types of cells, and the immunoproteasome, constitutively expressed in dendritic cells. Although both proteasome forms generate peptides for presentation by MHC I molecules, the immunoproteasome is the main form involved in providing peptide fragments for priming CD8 T cells. On the contrary, the proteasome provides peptides for presentation by MHC I molecules that can be targeted by already primed CD8 T cells. Proteasome cleavage prediction server (PCPS) is a server for predicting cleavage sites generated by both the constitutive proteasome and the immunoproteasome. Here, we illustrate the usage of PCPS to predict proteasome and immunoproteasome cleavage sites and compare the results with those provided by NetChop, a related tool available online. PCPS is implemented for free public use available online at

Key words

Proteasome Immunoproteasome Prediction of cleavage sites PCPS 



We wish to thank the Spanish department of science at MINECO for supporting the research of the immunomedicine group through grants SAF2006:07879, SAF2009:08301 and BIO2014:54164-R to P.A.R.


  1. 1.
    Kloetzel PM (2001) Antigen processing by the proteasome. Nat Rev Mol Cell Biol 2(3):179–187CrossRefGoogle Scholar
  2. 2.
    Blum JS, Wearsch PA, Cresswell P (2013) Pathways of antigen processing. Annu Rev Immunol 31:443–473CrossRefGoogle Scholar
  3. 3.
    Rock KL, Goldberg AL (1999) Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu Rev Immunol 17:739–779CrossRefGoogle Scholar
  4. 4.
    Craiu A, Akopian T, Goldberg A, Rock KL (1997) Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented peptide. Proc Natl Acad Sci U S A 94(20):10850–10855CrossRefGoogle Scholar
  5. 5.
    Dalet A, Stroobant V, Vigneron N, Van den Eynde BJ (2011) Differences in the production of spliced antigenic peptides by the standard proteasome and the immunoproteasome. Eur J Immunol 41(1):39–46CrossRefGoogle Scholar
  6. 6.
    Morel S, Levy F, Burlet-Schiltz O, Brasseur F, Probst-Kepper M, Peitrequin AL et al (2000) Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity 12(1):107–117CrossRefGoogle Scholar
  7. 7.
    Nielsen M, Lundegaard C, Lund O, Kesmir C (2005) The role of the proteasome in generating cytotoxic T-cell epitopes: insights obtained from improved predictions of proteasomal cleavage. Immunogenetics 57(1–2):33–41CrossRefGoogle Scholar
  8. 8.
    Rivett AJ, Hearn AR (2004) Proteasome function in antigen presentation: immunoproteasome complexes, peptide production, and interactions with viral proteins. Curr Protein Pept Sci 5(3):153–161CrossRefGoogle Scholar
  9. 9.
    Nussbaum AK, Kuttler C, Hadeler KP, Rammensee HG, Schild H (2001) PAProC: a prediction algorithm for proteasomal cleavages available on the WWW. Immunogenetics 53(2):87–94CrossRefGoogle Scholar
  10. 10.
    Tenzer S, Peters B, Bulik S, Schoor O, Lemmel C, Schatz MM et al (2005) Modeling the MHC class I pathway by combining predictions of proteasomal cleavage, TAP transport and MHC class I binding. Cell Mol Life Sci 62(9):1025–1037CrossRefGoogle Scholar
  11. 11.
    Holzhutter HG, Frommel C (1999) Kloetzel PM. A theoretical approach towards the identification of cleavage-determining amino acid motifs of the 20 S proteasome. J Mol Biol 286(4):1251–1265CrossRefGoogle Scholar
  12. 12.
    Kuttler C, Nussbaum AK, Dick TP, Rammensee HG, Schild H, Hadeler KP (2000) An algorithm for the prediction of proteasomal cleavages. J Mol Biol 298(3):417–429CrossRefGoogle Scholar
  13. 13.
    Bhasin M, Raghava GP (2005) Pcleavage: an SVM based method for prediction of constitutive proteasome and immunoproteasome cleavage sites in antigenic sequences. Nucleic Acids Res 33(Web Server issue):W202–W207CrossRefGoogle Scholar
  14. 14.
    Saxova P, Buus S, Brunak S, Kesmir C (2003) Predicting proteasomal cleavage sites: a comparison of available methods. Int Immunol 15(7):781–787CrossRefGoogle Scholar
  15. 15.
    Kesmir C, Nussbaum AK, Schild H, Detours V, Brunak S (2002) Prediction of proteasome cleavage motifs by neural networks. Protein Eng 15(4):287–296CrossRefGoogle Scholar
  16. 16.
    Diez-Rivero CM, Lafuente EM, Reche PA (2010) Computational analysis and modeling of cleavage by the immunoproteasome and the constitutive proteasome. BMC Bioinformatics 11:479CrossRefGoogle Scholar
  17. 17.
    Fleri W, Paul S, Dhanda SK, Mahajan S, Xu X, Peters B et al (2017) The immune epitope database and analysis resource in epitope discovery and synthetic vaccine design. Front Immunol 8:278CrossRefGoogle Scholar
  18. 18.
    Reche PA, Glutting JP, Zhang H, Reinherz EL (2004) Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles. Immunogenetics 56(6):405–419CrossRefGoogle Scholar
  19. 19.
    Reche PA, Glutting JP, Reinherz EL (2002) Prediction of MHC class I binding peptides using profile motifs. Hum Immunol 63(9):701–709CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Marta Gomez-Perosanz
    • 1
  • Alvaro Ras-Carmona
    • 1
  • Pedro A. Reche
    • 1
    Email author
  1. 1.Department of Immunology, School of MedicineComplutense University of MadridMadridSpain

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