PROSITE documentation PDOC00014
Endoplasmic reticulum targeting sequence


Proteins that permanently reside in the lumen of the endoplasmic reticulum (ER) seem to be distinguished from newly synthesized secretory proteins by the presence of the C-terminal sequence Lys-Asp-Glu-Leu (KDEL) [1,2]. While KDEL is the preferred signal in many species, variants of that signal are used by different species. This situation is described in the following table.

   Signal   Species
   KDEL     Vertebrates, Drosophila, Caenorhabditis elegans, plants
   HDEL     Saccharomyces cerevisiae, Kluyveromyces lactis, plants
   DDEL     Kluyveromyces lactis
   ADEL     Schizosaccharomyces pombe (fission yeast)
   SDEL     Plasmodium falciparum

The signal is usually very strictly conserved in major ER proteins but some minor ER proteins have divergent sequences (probably because efficient retention of these proteins is not crucial to the cell).

Proteins bearing the KDEL-type signal are not simply held in the ER, but are selectively retrieved from a post-ER compartment by a receptor and returned to their normal location.

The currently known ER luminal proteins are listed below.

  • Protein disulfide-isomerase (PDI) (also known as the β-subunit of prolyl 4-hydroxylase, as a component of oligosaccharyl transferase, as glutathione-insulin transhydrogenase and as a thyroid hormone binding protein).
  • ERp60, ERp72, and P5, three minor isoforms of PDI.
  • Trypanosoma brucei bloodstream-specific protein 2, a probable PDI.
  • hsp70 related protein GRP78 (also known as the immunoglobulin heavy chain binding protein (BiP), and as KAR2, in fungi).
  • hsp90 related protein 'endoplasmin' (also known as GRP94, Erp99 or Hsp108).
  • Calreticulin, a calcium-binding protein (also known as calregulin, CRP55, or HACBP).
  • ERC-55, a calcium-binding protein.
  • Reticulocalbin, a calcium-binding protein.
  • Hsp47, a heat-shock protein that binds strongly to collagen and could act as a chaperone in the collagen biosynthetic pathway.
  • A receptor for a plant hormone, auxin.
  • Thiol proteases from rice bean (SH-EP) and kidney bean (EP-C1).
  • Esterases from mammalian liver and from nematodes.
  • α-2-macroglobulin receptor-associated protein (RAP).
  • Yeast peptidyl-prolyl cis-trans isomerase D (CYPD).
  • Yeast protein KRE5, a protein required for (1->6)-β-D-glucan synthesis.
  • Yeast protein SEC20, required for the transport of proteins from the endoplasmic reticulum to the Golgi apparatus.
  • Yeast protein SCJ1, involved in protein sorting.
Last update:

November 1997 / Text revised.


Technical section

PROSITE method (with tools and information) covered by this documentation:

ER_TARGET, PS00014; Endoplasmic reticulum targeting sequence  (PATTERN)


1AuthorsMunro S. Pelham H.R.B.
TitleA C-terminal signal prevents secretion of luminal ER proteins.
SourceCell 48:899-907(1987).
PubMed ID3545499

2AuthorsPelham H.R.B.
TitleThe retention signal for soluble proteins of the endoplasmic reticulum.
SourceTrends Biochem. Sci. 15:483-486(1990).
PubMed ID2077689

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)