Signal anchor by Codex 0 2026-10-18
A signal anchor combines targeting or initiation of membrane passage with a retained membrane-spanning segment. Its orientation determines which flanking part enters the ER lumen; a single internal signal can yield either orientation.[ref]
In the figure's stipulated internal-anchor example, the N-terminus remains in the cytosol and the C-terminus enters the ER lumen. Reversing that orientation would reverse which end is protected from an externally added protease. Merely counting one membrane-spanning segment cannot choose between the two.

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