ER lumen protein-retaining receptor 1 (KDELR1)
The protein contains 212 amino acids for an estimated molecular weight of 24542 Da.
Receptor for the C-terminal sequence motif K-D-E-L that is present on endoplasmic reticulum resident proteins and that mediates their recycling from the Golgi back to the endoplasmic reticulum. (updated: May 8, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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Biological Process
Endoplasmic reticulum to Golgi vesicle-mediated transport
Intracellular protein transport
Protein retention in ER lumen
Protein transport
Retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
T cell apoptotic process
T cell cytokine production
T cell differentiation
Vesicle-mediated transport
Cellular Component
Cis-Golgi network
COPI-coated vesicle membrane
Endoplasmic reticulum
Endoplasmic reticulum membrane
Endoplasmic reticulum-Golgi intermediate compartment
Endoplasmic reticulum-Golgi intermediate compartment membrane
Golgi apparatus
Golgi membrane
Integral component of membrane
Membrane
Transport vesicle
The reference OMIM entry for this protein is 131235
Kdel endoplasmic reticulum protein retention receptor 1; kdelr1
Erd2, s. cerevisiae, homolog of; erd2
Hdel receptor, s. cerevisiae, homolog of
DESCRIPTION
Resident soluble proteins within the lumen of the endoplasmic reticulum (ER) are retained there by virtue of a C-terminal tetrapeptide ER retention signal, commonly lys-asp-glu-leu (KDEL) in mammals. KDELR1 cycles between the Golgi apparatus and the ER, returning proteins containing the KDEL signal to the ER (Lewis and Pelham, 1992).CLONING
By PCR of a T-cell cDNA library using degenerate primers based on yeast ERD2, followed by screening a placenta cDNA library, Lewis and Pelham (1990) cloned KDELR1. The deduced 212-amino acid protein has 7 hydrophobic regions and shares 50% identity with the yeast receptor. Following expression in COS cells, epitope tagged KDELR1 concentrated in the Golgi apparatus and in punctate structures that may have been transport vesicles or functional intermediates between the ER and Golgi.GENE FUNCTION
Lewis and Pelham (1992) found that overexpression of human ERD2 improved the retention of a protein with a weakly recognized variant of the KDEL retention signal, DDEL. Overexpression of KDEL or DDEL ligands caused redistribution of ERD2 from the Golgi apparatus to the ER, and mutation of ERD2 altered the ligand specificity of this redistribution. The authors concluded that ligand control of receptor movement may limit retrograde flow and minimize fruitless recycling of secretory proteins. Hsu et al. (1992) found that about half of KDELR1- or KDELR2 (609024)-transfected COS cells expressed the receptors in a juxtanuclear, Golgi-like pattern, while the remainder showed a reticular, ER-like pattern with nuclear envelope staining. Overexpression of the KDEL receptors led to the ER-like pattern and was associated with the collapse of the Golgi apparatus into the ER, as seen in cells treated with brefeldin A. In addition to the loss of the Golgi apparatus as a distinct organelle, overexpression resulted in redistribution of the Golgi coat protein, beta-COP (COPB; 600959), to the cytosol, addition of complex oligosaccharides to resident ER glycoproteins, and blockage of anterograde traffic. Hsu et al. (1992) concluded that the KDEL receptors provide signals that regulate retrograde traffic between the Golgi and the ER. Townsley et al. (1993) expressed mutant forms of KDELR1 in COS cells and examined their intracellular locations and ligand-binding capacities. They found that ligand binding was dependent on charged residues within the transmembrane domains. Retrograde transport of occupied receptors was unaffected by most mutations in the cytoplasmic loops, but was critically dependent upon asp193 in transmembrane domain 7. Retention in the Golgi apparatus required neither ligand binding nor asp193. Townsley et al. (1993) concluded that movement of the receptor is controlled by conformational changes and intermolecular interactions within the membrane bilayer.MAPPING
By genomic sequence analysis, Smith et al. (2000) mapped the KDELR1 gene to chromosome 19q13.3.ANIMAL MODEL
Hamada et al. (2004) created transgenic mice expressing a transport-defective human KDEL receptor. The mutant receptor sensitized cells to ER stress, and mutant mice developed dilated cardiomyopathy. Ultrastructural analysis revealed expanded sarcoplasmic reticulums and protein aggregates that obstructed the adjacent transverse tubules of mutant cardiomyocytes. Mutant cardiomyocytes were sensitive to ER stress following treatment with an N-glycosylation inhibitor, and they showed ... More on the omim web site
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for KDELR1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 131235 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed