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.
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
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,
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.
November 1997 / Text revised.
PROSITE method (with tools and information) covered by this documentation:
Munro S., Pelham H.R.B.
A C-terminal signal prevents secretion of luminal ER proteins.
PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to
or see: prosite_license.html.