A large number of integral proteins in eukaryotes do not traverse the membrane but are anchored in one or other leaflet of the bilayer through covalent attachment to a hydrocarbon chain. Several proteins, having the prion protein the causative  agent  of  mad  cow  disease  are  stably anchored  at  the  cell  surface by  covalent  linkage  of their  C-terminal  amino  acid  to the  headgroup  of a   phosphatidylinositol   lipid   by   an   ethanolamine-phosphate-trimannose-glucosamine   bridge,  so-called GPI (glycosyl  phosphatidylinositol)-anchored proteins. This difficult structure is built up by sequential addition of the individual sugar residues and ethanolamine phosphate to phosphatidylinositol. The C-terminal hydrophobic signal peptide is deleted from the protein in the lumen of the RER and the preformed GPI anchor added to the new exposed C- terminal amino acid.

figure: Lipid-modified proteins. (a) A glycosyl phosphatidylinositol-anchored protein (G, glucosamine; M, mannose; EtP, ethanolamine phosphate); (b) A myristoylated protein; (c) A prenylated protein; (d) a palmitoylated protein. Some proteins are also customized on Cys residues with covalently attached palmitate (C16:0) (palmitoylated proteins). These have some with membrane-spanning polypeptides (fig. 2d), some prenylated proteins and some myristoylated  proteins. Various of the proteins having in cell signaling, like as the G proteins and the Ras family of proteins are lipid modified.