A.
Some remain embedded in the ER membrane as transmembrane proteins. The translocation process for such proteins is more complicated than it is for soluble proteins, as some parts of the polypeptide chain must be translocated completely across the lipid bilayer, whereas other parts remain fixed within the membrane.
B.
In the simplest case, that of a transmembrane protein with a single membrane-spanning segment, the N-terminal signal sequence initiates translocation—as it does for a soluble protein. But the transfer process is then halted by an additional sequence of hydrophobic amino acids, a stop-transfer sequence, further along the polypeptide chain.
C.
At this point, the protein translocator releases the growing polypeptide chain sideways into the lipid bilayer. The N-terminal signal sequence is cleaved off, and the stop-transfer sequence remains in the bilayer, where it forms an α-helical membrane-spanning segment that anchors the protein in the membrane.
D.
As a result, the protein ends up as a single-pass transmembrane protein inserted in the membrane with a defined orientation—the N-terminus on the lumenal side of the lipid bilayer and the C-terminus on the cytosolic side. Once inserted into the membrane, a transmembrane protein will never change its orientation; its cytosolic portion will always remain in the cytosol, even if the protein is subsequently transported to another organelle via vesicle budding and fusion.