The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
KDEL retrieving signals
Functional site description:
The ER retrieving signals are used to retrieve escaped ER resident proteins from the Golgi apparatus, via a retrograde transport flow involving COPI-coated vesicles.
ELM Description:
KDEL retrieving signal is used to recycle ER resident proteins that are carried along with secretory proteins to post-ER compartments. COPI-coated vesicles mediate the retrograde transport of soluble ER resident proteins bearing a KDEL-type signal from the Golgi to the ER. This signal is recognized by the KDEL-receptor (ERD2), a seven transmembrane protein found mainly at the cis Golgi, which interacts with COPI. FRET studies have led to a model in which it is the binding of KDEL-bearing cargo to ERD2 that induces its oligomerisation and the formation of the budding complex in the cis Golgi, thus regulating its sorting into COPI-coated vesicles (Majoul,2001). The KDEL signal is cleaved during the activation of cysteine endopeptidase in the ricinosome of plants, a unique organelle originating from the ER and involved in senescence (Schmid,2001).
Pattern Probability: 0.0000016
Present in taxon: Eukaryota
Interaction Domain:
ER_lumen_recept (PF00810) ER lumen protein retaining receptor (Stochiometry: 1 : 1)
o See 13 Instances for TRG_ER_KDEL_1
o Abstract
ER-resident proteins such as chaperones or enzymes involved in post-translational modifications need to be retained in the ER compartment. They also can escape the ER compartment and therefore are recycled from the Golgi apparatus through an ER-to-Golgi retrograde transport. Some short linear motifs allow retention and or/retrieval of ER resident proteins that are carried along with secretory proteins to post-ER compartments.
ER lumen (soluble) proteins bear a KDEL motif at their C-terminus. KDEL is recognised by the KDEL-receptor (an integral membrane protein), which in turns binds to COPI (coatomer) underlying vesicles involved in the retrotransport, thus targeting its ligands to the COPI-mediated retrograde transport.
Other types of retrieving signals exist for ER integral membrane proteins, they interact directly with components of the coatomer through motifs located at the end of the proteins facing the cytoplasmic compartment (depending on their topology): the di-Lysine motif at the C-term (TRG_ER_diLys_1) and the di-Arginine motif at the N-terminus (TRG_ER_diArg_1).
The general criteria defining targeting motifs are that they function in a specific position of a protein, they can be disrupted through mutation, and that they confer residency in a specific organelle when engineered onto a reporter protein.
o 7 selected references:

o 11 GO-Terms:

o 13 Instances for TRG_ER_KDEL_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P13810 Heat-labile enterotoxin IIA, A chain
256 259 LTFFMSEDDFIGVHGERDEL TP 2 Escherichia coli
P09103 P4hb
506 509 EALEPDMEEDDDQKAVKDEL TP 1 Mus musculus (House mouse)
Q63010 Liver carboxy
558 561 VAFWTQLLAKRQPQPHHNEL TP 1 Rattus norvegicus (Norway rat)
P29457 Serpinh1
414 417 SLLFIGRLVRPKGDKMRDEL TP 1 Rattus norvegicus (Norway rat)
Q15293 RCN1
328 331 FVGSQATNYGEDLTKNHDEL TP 2 Homo sapiens (Human)
Q29092 HSP90B1
801 804 GADEEEQETSETSTAEKDEL TP 1 Sus scrofa (Pig)
P01555 ctxA
255 258 QIFSGYQSDIDTHNRIKDEL TP 3 Vibrio cholerae
Q8T9B6 boca
177 180 KGVTIENKEYPGVNAKKDEL TP 1 Drosophila melanogaster (Fruit fly)
P36604 bip1
660 663 GAGDADEEDDDYFDDEADEL TP 2 Schizosaccharomyces pombe (Fission yeast)
Q9ZNY3 Calreticulin
398 401 EEDEDDDDEEEEEDDKKDEL TP 1 Euglena gracilis
P13689 ABP1
P27797 CALR
414 417 EEDKEEDEEEDVPGQAKDEL TP 1 Homo sapiens (Human)
P11021 HSPA5
651 654 YGSAGPPPTGEEDTAEKDEL TP 1 Homo sapiens (Human)
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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