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- ********************************************
- * 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 disulphide-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).
- - The hsp70 related protein GRP78 (also known as the immunoglobulin heavy
- chain binding protein (BiP), and as KAR2, in fungi).
- - The hsp90 related protein 'endoplasmin' (also known as GRP94, Erp99, or
- Hsp108).
- - Calreticulin, a calcium-binding protein (also known as calregulin, CRP55,
- or HACBP).
- - 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).
- - ERp72, a mammalian protein of unknown function.
- - Trypanosoma brucei bloodstream-specific protein 2.
- - 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: [KRHSA]-[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: 17 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: June 1994 / Pattern and text revised.
-
- [ 1] Munro S., Pelham H.R.B.
- Cell 48:899-907(1987).
- [ 2] Pelham H.R.B.
- Trends Biochem. Sci. 15:483-486(1990).
-