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 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 AGESFPGIYDALFDIESKVDPSKAWGEVKRQIYVAAFTVQAAAETLSEVAProtein input sequence/s can be pasted or uploaded from a local file. Sequence uploading is achieved in two sequential steps, first browse/choose the local file with the sequences and second hit the upload bottom. This is done to facilitate preprocessing and error checking of input data prior to submission to the server.
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)
Frag. Size (N): This is the size of the peptide fragments in training and testing sets.
ECS: Expected Cleavage Sites. Calculated using the equation 100*C/(N-1) where C is the average number of cutpoint per fragment yield by a given model LMPCP when tested in a file of fragments size N.
MCC: Matthews Correlation Coefficient.
BTR: Better Than Random. Calculated as the difference between SE and ECS (BTR = SE - ECS). The bigger the difference between SE and ECS the better the prediction capacity of the model.
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.
E-mail is optional. If you enter a valid e-mail address you will be notified once the job is ready. You will be always
redirected to the result waiting page that will refresh until your job is completed.
|CONTACT: For any questions: Pedro Reche|