The fate of transmembrane proteins is determined at the rough endoplasmic reticulum (RER). Integral membrane proteins with the amino end exposed on the extracellular surface begin their lives like secreted proteins. Protein growth from the ribosome and extrusion in the RER lumen proceeds, but then hits a snag:

1. The protein gets stuck in the membrane at a hydrophobic sequence, a stop-transfer and anchor sequence.

2. The ribosome breaks free and finished translation in the cytosol, leaving the protein stuck - amino end unalterably facing into the RER lumen.

     Subsequent transport of the protein to the plasma membrane leaves it with its amino end facing outside the cell.