Identification of a consensus motif for retention of transmembrane proteins in the endoplasmic reticulum

• Published in: The EMBO journal 1990-10, Vol.9 (10), p.3153-3162
• Main Authors: Jackson, M. R., Nilsson, T., Peterson, P. A.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antigens, CD - genetics; Antigens, Differentiation, T-Lymphocyte - genetics; Base Sequence; Biological and medical sciences; CD8 Antigens; Cell membranes. Ionic channels. Membrane pores; Cell structures and functions; DNA, Recombinant - metabolism; Endoplasmic Reticulum - metabolism; Flow Cytometry; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; HeLa Cells - metabolism; Humans; Lysine; membrane proteins; Membrane Proteins - analysis; Membrane Proteins - genetics; Molecular and cellular biology; Molecular Sequence Data; Mutation; Oligonucleotide Probes; Sequence Homology, Nucleic Acid
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1990.tb07513.x

Several families of transmembrane endoplasmic reticulum (ER) proteins contain retention motifs in their cytoplasmically exposed tails. Mutational analyses demonstrated that two lysines positioned three and four or five residues from the C‐terminus represent the retention motif. The introduction of a lysine preceding the lysine that occurs three residues from the terminus of Lyt2 renders this cell surface protein a resident of the ER. Likewise, the appropriate positioning of two lysine residues in a poly‐serine sequence confines marker proteins to the ER. Arginines or histidines cannot replace lysines, suggesting that simple charge interactions are not sufficient to explain the retention. The identified consensus motif may serve as a retrieval signal that brings proteins back from a sorting compartment adjacent to the ER.