{PDOC00014}
{PS00014; ER_TARGET}
{BEGIN}
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* Endoplasmic reticulum targeting sequence *
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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 beta-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.
 - Alpha-2-macroglobulin receptor-associated protein (RAP).
 - Yeast peptidyl-prolyl cis-trans isomerase D (CYPD).
 - Yeast protein KRE5, a protein required for (1->6)-beta-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.

-Consensus pattern: [KRHQSA]-[DENQ]-E-L>
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for liver esterases which have H-[TVI]-E-L.
-Other sequence(s) detected in Swiss-Prot: 24 proteins which  are  clearly not
 located in  the  ER  (because  they  are  of  bacterial  or viral origin, for
 example) and a protein which can be considered as valid candidate: human 80K-
 H protein.
-Last update: November 1997 / Text revised.

[ 1] Munro S., Pelham H.R.B.
     "A C-terminal signal prevents secretion of luminal ER proteins."
     Cell 48:899-907(1987).
     PubMed=3545499
[ 2] Pelham H.R.B.
     "The retention signal for soluble proteins of the endoplasmic
     reticulum."
     Trends Biochem. Sci. 15:483-486(1990).
     PubMed=2077689

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