Non Classical Secretion
For targeting a protein to the extracellular space, it has for a long time been believed that an N-terminal signal peptide was strictly required. Recent studies, however, have shown that several extracellular proteins, such as FGF-1, FGF-2, IL-1 and galectins found in the extracellular matrix, can be exported without a classical N-terminal signal peptide. Furthermore, nuclear HMGB1 and viral proteins, such as HIV-tat or herpes simplex virus VP22, have been shown to enter the non-classical secretory pathway. Secretion of proteins without an N-terminal signal peptide is currently known as leaderless secretion or the non-conventional/non-classical secretory pathway.
This is a catalogue of verified and predicted human proteins undergoing non-classical secretion, i.e. proteins without an N-terminal signal peptide.
Verified non-classical secreted proteins in Humans
Predicted non-classical secreted proteins in Humans
Human proteins from Swiss-Prot entering the non-classical sectory pathway.
The list of predicted human proteins, entering the non-classical secretory pathway, is generated using a sequence based prediction method SecretomeP. The method is based on protein features like different physiochemical properties, post-translational modifications or structural motifs.
Version 3.05 (April 2005) of the human IPI database have been analyzed by SecretomeP. Links to the results are listed below. Proteins are ranked after highest neural network score.
- List A: Contain all proteins from IPI ranked by SecretomeP.
- List B: Proteins predicted to have a sigal peptide from list A are removed.
- List C: Contain only proteins from list B where the odds is > 5.0.
- List D: Is a fasta file of all proteins from list C which have a methionine start codon. This list is sorted by IPI accession number and begin with the lowest.
- List E: Are proteins from List D which are not predicted to be transmembrane proteins after running TMHMM. List E is in fasta file format and sorted by IPI accession number and begin with the lowest.
The list below is the top-thirty highest scoring human entries from SecretomeP and after stratifications mentioned above (No signal peptide, odds >5, M start codon, TMHMM = 0). All entries share significant homology to mouse sequences.
IPI NN Description in NR
00051307.4 0.985 Similar to hypothetical protein zc477.8
00006018.1 0.974 Hypothetical protein DKFZp434N0450
00008308.1 0.972 HGC6.3 protein
00397223.2 0.971 Similar to SMART/HDAC1 associated repressor protein
00444615.1 0.970 Hypothetical protein FLJ45073
00442531.1 0.968 Hypothetical protein FLJ27057
00234905.7 0.968 Unnamed protein product
00097028.1 0.968 Hypothetical protein XP_087208
00456168.1 0.964 Hypothetical protein XP_498608
00046805.1 0.964 Hypothetical protein XP_059473
00444711.1 0.963 Hypothetical protein FLJ44998
00176065.1 0.962 Hypothetical protein XP_211768
00553011.1 0.961 Mitogen-activated protein kinase associated protein 1 (fragment)
00455120.1 0.961 Hypothetical protein XP_499572
00402230.1 0.961 Similar to Mucin 4 (Tracheobronchial mucin)
00386457.1 0.961 OK/SW-CL.41
00014395.1 0.961 -
00450969.1 0.959 Hypothetical protein
00444414.1 0.959 Hypothetical protein FLJ45598
00384290.3 0.959 Hypothetical protein
00454901.1 0.958 Similar to CG7709-PA
00402418.1 0.958 Hypothetical protein XP_379189
00235542.1 0.958 Hypothetical protein XP_295126
00457129.1 0.957 Similar to KIAA0754 protein.
00031070.1 0.957 Hypothetical protein
00445342.1 0.956 Hypothetical protein FLJ44184
00552576.1 0.955 Novel protein
00022319.1 0.955 NPD002
00445898.1 0.953 Hypothetical protein FLJ43291
00434875.2 0.953 Hypothetical protein LOC130074
The SecretomeP method complements the highly popular method for detection of classically secreted proteins, SignalP.
More details about the SecretomeP method can be found in the paper:
"Feature based prediction of non-classical and leaderless protein secretion"
J. Dyrløv Bendtsen, L. Juhl Jensen, N. Blom, G. von Heijne and S. Brunak.
Protein Eng Des Sel, 2004 17(4), 349-356.
Predictions can be made at SecretomeP server.
This page is part of the BioSapiens Network funded by the European Commission within its FP6 programme, under the thematic area "Life science, genomics and biotechnology for health", contract number LHSG-CT-2003-503265.