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Surface proteins are typically located on the outer or inner surfaces of the cell membrane, interacting with the extracellular environment or cytoplasm, whereas membrane-spanning proteins, also known as transmembrane proteins, extend across the lipid bilayer and have regions that interact with both the extracellular space and the cytoplasm. This structural difference allows surface proteins to function primarily in signaling and recognition, while membrane-spanning proteins often serve roles in transport, communication, and structural support.

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