A COOH-terminal double lysine motif maintains type I transmembrane pro
teins in the ER. Proteins tagged with this motif, eg., CD8/E19 and CD4
/E19, rapidly receive post-translational modifications characteristic
of the intermediate compartment and partially colocalized to this orga
nelle. These proteins also received modifications characteristic of th
e Golgi but much more slowly. Lectin staining localized these Golgi mo
dified proteins to ER indicating that this motif is a retrieval signal
. Differences in the subcellular distribution and rate of post-transla
tional modification of CD8 maintained in the ER by sequences derived f
rom a variety of ER resident proteins suggested that the efficiency of
retrieval was dependent on the sequence context of the double lysine
motif and that retrieval may be initiated from multiple positions alon
g the exocytotic pathway.