PCPS
Proteasome Cleavage Prediction Server

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• BACKGROUND
• USER GUIDE
• Input
• Cleavage models
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• Output
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       The proteasome is the main responsible of proteolytic degradation of cytosolic proteins, generating protein fragments between 7 and 15 amino acids. Some of these peptides can be transported into the endoplasmic reticulum by TAP. Whereas proteases of the endoplasmic reticulum trim amino acids from the amino-terminus of the peptides the carboxy-terminus of MHCI peptide ligands is generated by the proteasome. Therefore the proteasome plays a central role in the MHCI antigen processing pathway. There are two different proteasomes, the constitutive proteasome, presented in all types of cells, and the immunoproteasome, constitutively presented only in dendritic cells. 
       PCPS is a server for the prediction of cleavage sites generated by both, the constitutive proteasome and the immunoproteasome

Input

       Input query for PCPS can be one or more protein sequences in FASTA, GenBank, EMBL or Phylip formats. Example of a protein sequence in FASTA Format.

>A56881  PIR2 release 71.00 
MWNLLHETDSAVATARRPRWLCAGALVLAGGFFLLGFLFGWFIKSSNEAT
NITPKHNMKAFLDELKAENIKKFLYNFTQIPHLAGTEQNFQLAKQIQSQW
KEFGLDSVELAHYDVLLSYPNKTHPNYISIINEDGNEIFNTSLFEPPPPG
YENVSDIVPPFSAFSPQGMPEGDLVYVNYARTEDFFKLERDMKINCSGKI
VIARYGKVFRGNKVKNAQLAGAKGVILYSDPADYFAPGVKSYPDGWNLPG
GGVQRGNILNLNGAGDPLTPGYPANEYAYRRGIAEAVGLPSIPVHPIGYY
DAQKLLEKMGGSAPPDSSWRGSLKVPYNVGPGFTGNFSTQKVKMHIHSTN
EVTRIYNVIGTLRGAVEPDRYVILGGHRDSWVFGGIDPQSGAAVVHEIVR
SFGTLKKEGWRPRRTILFASWDAEEFGLLGSTEWAEENSRLLQERGVAYI
NADSSIEGNYTLRVDCTPLMYSLVHNLTKELKSPDEGFEGKSLYESWTKK
SPSPEFSGMPRISKLGSGNDFEVFFQRLGIASGRARYTKNWETNKFSGYP
LYHSVYETYELVEKFYDPMFKYHLTVAQVRGGMVFELANSIVLPFDCRDY
AVVLRKYADKIYSISMKHPQEMKTYSVSFDSLFSAVKNFTEIASKFSERL
QDFDKSNPIVLRMMNDQLMFLERAFIDPLGLPDRPFYRHVIYAPSSHNKY
AGESFPGIYDALFDIESKVDPSKAWGEVKRQIYVAAFTVQAAAETLSEVA

Cleavage models

      The user can select a single cleavage prediction model, proteasome or immunoproteasome, or both models simultaneously. The different available models correspond to the constitutive proteasome (PCP-p) or the immunoproteasome (PCP-ip), models were trained on 382 MHCI-eluted peptide ligands and 553 CD8 T cell epitopes and their flanking regions, respectively.PCPs were obtained using N-GRAM-COUNT and tested using HIDDEN-NGRAM. Different models were obtained from different training sets consisting of peptide fragments containing the carboxy-terminus (P1 residue of cleavage site) of the MHCI-restricted peptides (MHCI-eluted peptides and CD8 T cell epitopes) and a variable number of flanking residues. The predictive cleavage models for proteasome (PCP-p) and immunoproteasome (PCP-ip) available in PCPS are the following:

Model	Frag. Size (N)	SE	SP	ECS	MCC	BTR
model 1: PCP-p12	12	0.87 (± 0.03)	0.53 (± 0.06)	0.35 (± 0.02)	0.43 (± 0.07)	0.53 (± 0.02)
model 2: PCP-p8	8	0.85 (± 0.04)	0.60 (± 0.05)	0.38 (± 0.02)	0.47 (± 0.07)	0.47 (± 0.02)
model 3: PCP-p6	6	0.79 (± 0.05)	0.72 (± 0.04)	0.52 (± 0.08)	0.36 (± 0.02)	0.43 (± 0.03)
model 1: PCP-ip12	12	0.90 (± 0.03)	0.41 (± 0.03)	0.46 (± 0.01)	0.36 (± 0.06)	0.44 (± 0.01)
model 2: PCP-ip8	8	0.91 (± 0.02)	0.54 (± 0.04)	0.51 (± 0.01)	0.48 (± 0.06)	0.39 (± 0.01)
model 3: PCP-ip6	6	0.76 (± 0.04)	0.71 (± 0.04)	0.39 (± 0.01)	0.47 (± 0.07)	0.38 (± 0.02)

Output

       The server will compute cleavage prediction after each residue of the protein by the proteasome and/or the immunoproteasome and return a table with all the residues and their cleavage prediction score, marking with a tick when the score is > 0.5. When both, proteasome and immunoproteasome, are selected, the server return a table with both cleavage predictions. Here follows a representative output.

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