Consensus N-terminal Secretory Signal Peptide
A generic representation of N-terminal signal peptides that direct newly synthesized proteins to the ER lumen and secretory pathway. Commonly used examples include the IgK leader, IL-2 signal peptide, and mouse Ig heavy chain signal. This entry represents the class rather than a single sequence.
Origin: Various mammalian secretory proteins (IgK, IL-2, albumin, etc.)
Characteristics
Tripartite structure: positively charged n-region, hydrophobic h-region (~10 aa), c-region with signal peptidase cleavage site (A-X-A motif). Cleaved co-translationally by signal peptidase in ER lumen. Cargo ends up secreted or membrane-integrated depending on downstream sequences.
Applications
Directing antibody chains, cytokines, growth factors, and secreted reporters to the secretory pathway. Required for all ER-targeted proteins. Used in AAV-delivered secreted therapeutic payloads.
Limitations
Signal peptide efficiency is context-dependent—the downstream protein sequence can affect cleavage efficiency and targeting. Not all signal peptides work equally well for all cargo. IgK leader is generally preferred for antibody applications; species-matched signals preferred for expression in specific cell types.
Literature References
- von Heijne et al. (1990). The signal peptide. J Membr Biol - vonHeijne 1990 Signal Peptides