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The attachment of a GPI anchor to a protein in the ER. GPI-anchored proteins are targeted to the ER membrane by an N-terminal signal sequence (not shown), integrated into the membrane, and processed by signal peptidase similarly to a single-pass transmembrane protein (see Figure 12–27). Immediately after the completion of protein synthesis, the precursor protein remains anchored in the ER membrane by a hydrophobic C-terminal sequence of 15–20 amino acids; the rest of the protein is in the ER lumen. Within less than a minute, a transamidase enzyme in the ER cleaves the protein from its membrane-bound C-terminus and simultaneously attaches the new C-terminus to an amino group on a preassembled GPI intermediate. The sugar chain contains an inositol attached to the lipid from which the GPI anchor derives its name. It is followed by a glucosamine and three mannoses. The terminal mannose links to a phosphoethanolamine that provides the amino group to attach the protein through an amide bond. The signal that specifies this modification is contained within the hydrophobic C-terminal sequence and a few amino acids adjacent to it on the lumenal side of the ER membrane; if this signal is added to other proteins, they too become modified in this way. Because of the covalently linked lipid anchor, the protein remains membrane-bound, with all of its amino acids exposed initially on the lumenal side of the ER and eventually on the exterior of the plasma membrane