Endoplasmic Reticulum

ID #1857

What is the difference between the "signal sequence" on the protein that has its C terminus in the cytoplasm and the "internal signal sequence" on the protein that has its N terminus in the cytoplasm? Also, this might be a dumb question, but how do we know how many times a protein is supposed to span the membrane, and whether or not the C and N terminus will be on the same side?

Knowing where the C terminus is doesn't directly tell you anything about the signal peptide that got you to the ER to begin with. If the N terminus is in the lumen of the ER, then the first signal that was presented was an amino terminal signal sequence which has been removed, but that doesn't mean the C terminus is necessarily going to end up in the cytoplasm.

To predict where the termini end up and how many times it spans the membrane, you first identify what the first presented signal is, then alternate stop and start signals, where each one (other than an amino terminal signal sequence) represents a membrane spanning region. For example, a protein with an internal signal sequence as its first signal, followed by a stop transfer sequence and another internal signal sequence would span the membrane three times, have its N terminus in the cytoplasm, and its C terminus in the lumen (or exposed to the extracellular space).

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