[5] Retention of resident soluble proteins in the lumen of the endoplasmic reticulum (ER) is achieved in both yeast and animal cells by their continual retrieval from the cis-Golgi, or a pre-Golgi compartment.

Sorting of these proteins is dependent on a C-terminal tetrapeptide signal, lys-asp-glu-leu (KDEL) in animal cells and his-asp-glu-leu (HDEL) in S. cerevisiae.

This process is mediated by a receptor that recognizes, and binds the tetrapeptide-containing protein, and returns it to the ER.

In yeast, the sorting receptor encoded by a single gene, ERD2, is a seven-transmembrane protein.

Two transcript variants of KDELR3 that arise by alternative splicing, and encode different isoforms of KDELR3 receptor, have been described.