Abstract
Membrane proteins can contain short sequence motifs that determine their intracellular location, either by a retention or a retrieval mechanism. In both cases the targeting signal is essentially a specific binding site for other proteins that effect the localization. The folding of targeting motifs is often robust leading to a dominant effect in molecular cut and paste experiments designed to identify them. However regulation can also occur, allowing a single membrane protein to express different targeting signals at different locations in the cell. Regulation can be achieved by phosphorylation of the cytoplasmic domain leading to changes in binding affinity for effector proteins, or by masking of the targeting signal by complex formation.