Signal peptide

A signal peptide is a short targeting segment of a newly made polypeptide chain. A familiar ER signal sequence lies near the N-terminus and is removed during entry; Günter Blobel and Bernhard Dobberstein's 1975 experiments linked a larger immunoglobulin light chain precursor to a processed product.^[ref]

Cleavage is a separate question from recognition. Not every targeting signal is a cleaved signal peptide: an internal signal anchor can remain part of a transmembrane protein. Conversely, loss of a segment does not by itself prove membrane crossing. Compare the independent size and accessibility readouts in the microsomal protein import experiment.

A signal peptidase removes a cleavable signal peptide; a suitable cleavage site and access are required.^[ref]

For the stipulated $180$-amino acid residue precursor under ER signal sequence, removal of the first $20$ amino acid residues leaves $160$. Now stipulate that positions $101$–$120$ of that precursor are instead retained as a stop-transfer sequence. Their positions in the mature chain become $81$–$100$, because the numbering origin changes when the first $20$ positions are removed. The mature chain still has $160$ amino acid residues, but its membrane-spanning segment is retained. A second hypothetical chain with an uncleaved internal signal anchor loses no positions at all. These are conditional bookkeeping examples, not predictions from invented biological sequences.