Gene Symbol: KDELR1
Description: KDEL endoplasmic reticulum protein retention receptor 1
Alias: ERD2, ERD2.1, HDEL, PM23, ER lumen protein-retaining receptor 1, KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 1, KDEL receptor 1
Species: human
Products:     KDELR1

Top Publications

  1. Lewis M, Pelham H. A human homologue of the yeast HDEL receptor. Nature. 1990;348:162-3 pubmed
    ..tetrapeptide signal, usually Lys-Asp-Glu-Leu (KDEL in the single letter code) in animal cells, His-Asp-Glu-Leu (HDEL) in Saccharomyces cerevisiae...
  2. Townsley F, Wilson D, Pelham H. Mutational analysis of the human KDEL receptor: distinct structural requirements for Golgi retention, ligand binding and retrograde transport. EMBO J. 1993;12:2821-9 pubmed
    ..We suggest that movement of the receptor is controlled by conformational changes and intermolecular interactions within the membrane bilayer. ..
  3. Wang P, Li B, Zhou L, Fei E, Wang G. The KDEL receptor induces autophagy to promote the clearance of neurodegenerative disease-related proteins. Neuroscience. 2011;190:43-55 pubmed publisher
    ..Taken together, our data provide evidence that KDELR, as a novel inducer of autophagy, participates in the degradation of misfolded neurodegenerative disease-related proteins. ..
  4. Giannotta M, Ruggiero C, Grossi M, Cancino J, Capitani M, Pulvirenti T, et al. The KDEL receptor couples to G?q/11 to activate Src kinases and regulate transport through the Golgi. EMBO J. 2012;31:2869-81 pubmed publisher
    ..These findings reveal an unexpected GPCR-like mode of action of the KDEL-R and shed light on a core molecular control mechanism of intra-Golgi traffic. ..
  5. Abrams E, Cheng Y, Andrew D. Drosophila KDEL receptor function in the embryonic salivary gland and epidermis. PLoS ONE. 2013;8:e77618 pubmed publisher
    ..We show that, unlike Saccharomyces cerevisiae Erd2 mutants, which are viable, KdelR mutations are early larval lethal, with homozygous mutant animals dying as first ..
  6. Bartels A, Göttert S, Desel C, Schäfer M, Krossa S, Scheidig A, et al. KDEL Receptor 1 Contributes to Cell Surface Association of Protein Disulfide Isomerases. Cell Physiol Biochem. 2019;52:850-868 pubmed publisher
    ..The cell surface trafficking of PDIA1, PDIA3, and PDIA6 is dependent on KDELR1, which travels in a dynamic manner to the cell surface...
  7. Jin N, Lee J, Heo W, Ryu M, So M, Ko B, et al. Low binding affinity and reduced complement-dependent cell death efficacy of ofatumumab produced using a plant system (Nicotiana benthamiana L.). Protein Expr Purif. 2019;159:34-41 pubmed publisher
    ..Two forms of plant ofatumumab (with or without HDEL-tag) were generated and their production yields were compared...
  8. An Y, DiTrani Lobacz A, Lehmann T, Baumeister J, Rose W, Higginson J, et al. Neuroplastic changes in anterior cruciate ligament reconstruction patients from neuromechanical decoupling. Scand J Med Sci Sports. 2019;29:251-258 pubmed publisher
    ..1% ± 14.2%, P = 0.001). Higher somatosensory cortical activity during midloading (ERD2) to the ACLR knee positively correlated with knee laxity (mm) during early loading (LAX1, r = 0...
  9. Kim T, Kwon O, Song J. Response prediction of nonlinear hysteretic systems by deep neural networks. Neural Netw. 2019;111:1-10 pubmed publisher
    ..The supporting source code and data are available for download at https://github.com/TyongKim/ERD2.

More Information


  1. Trychta K, Bäck S, Henderson M, Harvey B. KDEL Receptors Are Differentially Regulated to Maintain the ER Proteome under Calcium Deficiency. Cell Rep. 2018;25:1829-1840.e6 pubmed publisher
    ..In addition, we provide evidence that KDELR2 and KDELR3, but not KDELR1, are unfolded protein response (UPR) genes upregulated as an adaptive response to counteract the loss of ERS-..
  2. Goh J, Jeon J, Lee Y. ER retention receptor, MoERR1 is required for fungal development and pathogenicity in the rice blast fungus, Magnaporthe oryzae. Sci Rep. 2017;7:1259 pubmed publisher
    ..Magnaporthe oryzae identified MoERR1 as a pathogenicity gene encoding putative ER retention receptor orthologous to ERD2 in Saccharomyces cerevisiae. Search through the genome identified that M...
  3. Wang H, Shao Y, Zhang W, Li C, Lv Z, Jin C. Molecular characterization of two novel molecular chaperones in bacterial-challenged Apostichopus japonicus. Gene. 2015;570:141-9 pubmed publisher
    ..AjGRP78 contained a 23-amino acid signal peptide at the N-terminus and a HDEL motif at the C-terminus, which supported the location of the protein in the ER...
  4. Montesinos J, Pastor Cantizano N, Robinson D, Marcote M, Aniento F. Arabidopsis p24δ5 and p24δ9 facilitate Coat Protein I-dependent transport of the K/HDEL receptor ERD2 from the Golgi to the endoplasmic reticulum. Plant J. 2014;80:1014-30 pubmed publisher
    ..Here, we show that Arabidopsis p24δ5/δ9 and HDEL ligands shift the steady-state distribution of the K/HDEL receptor ERD2 from the Golgi to the ER...
  5. Silva Alvim F, An J, Alvim J, Foresti O, Grippa A, Pelgrom A, et al. Predominant Golgi Residency of the Plant K/HDEL Receptor Is Essential for Its Function in Mediating ER Retention. Plant Cell. 2018;30:2174-2196 pubmed publisher
    ..proteins in the endoplasmic reticulum (ER) of plants is mediated by a receptor termed ER RETENTION DEFECTIVE2 (ERD2) or K/HDEL receptor...
  6. Borhani Dizaji N, Basseri H, Naddaf S, Heidari M. Molecular characterization of calreticulin from Anopheles stephensi midgut cells and functional assay of the recombinant calreticulin with Plasmodium berghei ookinetes. Gene. 2014;550:245-52 pubmed publisher
    ..residues, a proline-rich region, and highly acidic C-terminal domain with endoplasmic reticulum retrieval sequence HDEL. The production of GST-AsCrt recombinant protein was confirmed by Western blot analysis using an antibody against ..
  7. Wang G, Jiang Z, Zhang M, Yang N, Zhu D. Identification of a new calreticulin homolog from Yesso scallop (Patinopecten yessoensis) and its role in innate immunity. Fish Shellfish Immunol. 2016;58:108-115 pubmed publisher
    ..domains (N-, P- and C-domains), a signal peptide and an endoplasmic reticulum (ER) retrieval signal sequence (HDEL)...
  8. Kamimura D, Katsunuma K, Arima Y, Atsumi T, Jiang J, Bando H, et al. KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR. Nat Commun. 2015;6:7474 pubmed publisher
    ..Here we describe a role for KDEL receptor 1 (KDELR1) that involves the regulation of integrated stress responses (ISR) in T cells...
  9. Singh P, Savithri H. GBNV encoded movement protein (NSm) remodels ER network via C-terminal coiled coil domain. Virology. 2015;482:133-46 pubmed publisher
    ..Furthermore, mCherry:NSm co-localized with ER-GFP (endoplasmic reticulum targeting peptide (HDEL peptide fused with GFP)...
  10. Oh hashi K, Soga A, Naruse Y, Takahashi K, Kiuchi K, Hirata Y. Elucidating post-translational regulation of mouse CREB3 in Neuro2a cells. Mol Cell Biochem. 2018;448:287-297 pubmed publisher
    ..and co-transfection with genes associated with ER-Golgi homeostasis, such as mutant Sar1 [H79G], GRP78, and KDEL receptor 1 (KDELR1)...
  11. Shibuya A, Margulis N, Christiano R, Walther T, Barlowe C. The Erv41-Erv46 complex serves as a retrograde receptor to retrieve escaped ER proteins. J Cell Biol. 2015;208:197-209 pubmed publisher
    ..In this study, we identify the Erv41-Erv46 complex as a new retrograde receptor for retrieval of non-HDEL-bearing ER resident proteins...
  12. Arakel E, Richter K, Clancy A, Schwappach B. ?-COP contains a helix C-terminal to its longin domain key to COPI dynamics and function. Proc Natl Acad Sci U S A. 2016;113:6916-21 pubmed publisher
    ..uncharacterized helix, C-terminal to the longin domain, that is specifically required for the retrieval of HDEL-bearing endoplasmic reticulum-luminal residents...
  13. Hou J, Li X, Li C, Sun L, Zhao Y, Zhao J, et al. Plasma membrane gp96 enhances invasion and metastatic potential of liver cancer via regulation of uPAR. Mol Oncol. 2015;9:1312-23 pubmed publisher
    ..Decreased KDELR1 levels in hepatoma cells contribute to cell membrane translocation of the normally ER-resident gp96...
  14. Pastor Cantizano N, Montesinos J, Bernat Silvestre C, Marcote M, Aniento F. p24 family proteins: key players in the regulation of trafficking along the secretory pathway. Protoplasma. 2016;253:967-85 pubmed publisher
    ..to modulate the transport of specific cargos, including GPI-anchored proteins, G-protein-coupled receptors, or K/HDEL ligands...
  15. Siggs O, Popkin D, Krebs P, Li X, Tang M, Zhan X, et al. Mutation of the ER retention receptor KDELR1 leads to cell-intrinsic lymphopenia and a failure to control chronic viral infection. Proc Natl Acad Sci U S A. 2015;112:E5706-14 pubmed publisher
    ..recessive mouse missense allele of the prototypical mammalian KDEL receptor, KDEL ER protein retention receptor 1 (KDELR1). Kdelr1 homozygous mutants were mildly lymphopenic, as were mice with a CRISPR/Cas9-engineered frameshift allele...
  16. Kamimura D, Arima Y, Tsuruoka M, Jiang J, Bando H, Meng J, et al. Strong TCR-mediated signals suppress integrated stress responses induced by KDELR1 deficiency in naive T cells. Int Immunol. 2016;28:117-26 pubmed publisher
    b>KDEL receptor 1 (KDELR1) regulates integrated stress responses (ISR) to promote naive T-cell survival in vivo...
  17. Xie W, Nielsen M, Pedersen C, Thordal Christensen H. A Split-GFP Gateway Cloning System for Topology Analyses of Membrane Proteins in Plants. PLoS ONE. 2017;12:e0170118 pubmed publisher
    ..We observed GFP signal from the ER when we reciprocally co-expressed GFP11-CNXTM with GFP1-10-HDEL and CNXTM-GFP with cytosolic GFP1-10. The opposite combinations did not result in GFP signal emission...
  18. Udayantha H, Godahewa G, Bathige S, Wickramaarachchi W, Umasuthan N, De Zoysa M, et al. A molluscan calreticulin ortholog from Haliotis discus discus: Molecular characterization and transcriptional evidence for its role in host immunity. Biochem Biophys Res Commun. 2016;474:43-50 pubmed publisher
    ..In contrast, the C-domain which terminated with the characteristic ER retrieval signal (HDEL) was relatively less conserved...
  19. Pastor Cantizano N, Bernat Silvestre C, Marcote M, Aniento F. Loss of Arabidopsis p24 function affects ERD2 trafficking and Golgi structure, and activates the unfolded protein response. J Cell Sci. 2018;131: pubmed publisher
    ..the early secretory pathway in Arabidopsis Loss of p24δ-1 proteins also induced the accumulation of the K/HDEL receptor ERD2a (ER lumen protein-retaining receptor A) at the Golgi and increased secretion of BiP family proteins, ..
  20. Dominguez M, Dejgaard K, Fullekrug J, Dahan S, Fazel A, Paccaud J, et al. gp25L/emp24/p24 protein family members of the cis-Golgi network bind both COP I and II coatomer. J Cell Biol. 1998;140:751-65 pubmed
    ..Surprisingly, upon expression of mutated members, steady-state distribution of unmutated ones shifted as well, presumably as a consequence of their observed oligomeric properties. ..
  21. Aoe T, Cukierman E, Lee A, Cassel D, Peters P, Hsu V. The KDEL receptor, ERD2, regulates intracellular traffic by recruiting a GTPase-activating protein for ARF1. EMBO J. 1997;16:7305-16 pubmed
    ..Here, we demonstrate that the intracellular KDEL receptor, ERD2, self-oligomerizes and interacts with ARF1 GAP, and thereby regulates the recruitment of cytosolic ARF1 GAP to ..
  22. Pastor Cantizano N, García Murria M, Bernat Silvestre C, Marcote M, Mingarro I, Aniento F. N-Linked Glycosylation of the p24 Family Protein p24?5 Modulates Retrograde Golgi-to-ER Transport of K/HDEL Ligands in Arabidopsis. Mol Plant. 2017;10:1095-1106 pubmed publisher
    The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER)-resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles...
  23. Lewis M, Pelham H. Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum. Cell. 1992;68:353-64 pubmed
    ..In yeast, the receptor that promotes this selective retrograde transport has been identified as the product of the ERD2 gene. We describe here the properties of a human homolog of this protein (hERD2)...
  24. Giannotta M, Fragassi G, Tamburro A, Vanessa C, Luini A, Sallese M. Prohibitin: A Novel Molecular Player in KDEL Receptor Signalling. Biomed Res Int. 2015;2015:319454 pubmed publisher
    ..We propose a model whereby in analogy to previous findings (e.g., the RAS-RAF signalling pathway), PHB can act as a signalling scaffold protein to assist in KDELR-dependent Src activation. ..
  25. Smith J, Tachibana I, Pohl U, Lee H, Thanarajasingam U, Portier B, et al. A transcript map of the chromosome 19q-arm glioma tumor suppressor region. Genomics. 2000;64:44-50 pubmed
    ..Tumor-specific alterations have not been identified in the transcripts examined thus far. Collectively, these data should facilitate subsequent efforts to identify and characterize the remaining transcripts in the 1.6-Mb interval. ..
  26. Bard F, Mazelin L, Péchoux Longin C, Malhotra V, Jurdic P. Src regulates Golgi structure and KDEL receptor-dependent retrograde transport to the endoplasmic reticulum. J Biol Chem. 2003;278:46601-6 pubmed
    ..We propose that Src has an appreciable role in the organization of the Golgi apparatus, which may be linked to its involvement in protein transport from the Golgi apparatus to the endoplasmic reticulum. ..
  27. Wang R, Wu Y, Chen H, Chen C. A KDEL Retrieval System for ER-Golgi Transport of Japanese Encephalitis Viral Particles. Viruses. 2016;8: pubmed publisher
    ..Altogether, we demonstrated that intracellular trafficking of JE assembled viral particles was mediated by the host ER-Golgi retrieval system prior to exit by the secretory pathway. ..
  28. Cancino J, Jung J, Luini A. Regulation of Golgi signaling and trafficking by the KDEL receptor. Histochem Cell Biol. 2013;140:395-405 pubmed publisher
    ..Here, we discuss the particular role of KDEL receptor signaling in the regulation of important pathways involved in the maintenance of the homeostasis of the transport apparatus, and in particular, of the Golgi complex. ..
  29. Pelham H. The dynamic organisation of the secretory pathway. Cell Struct Funct. 1996;21:413-9 pubmed
    ..The secretory pathway is thus a dynamic entity, split into discrete organelles by the constant segregation and recycling of lipids and proteins, processes that are ultimately driven by the mechanics of vesicle formation and fusion. ..
  30. Yamamoto K, Hamada H, Shinkai H, Kohno Y, Koseki H, Aoe T. The KDEL receptor modulates the endoplasmic reticulum stress response through mitogen-activated protein kinase signaling cascades. J Biol Chem. 2003;278:34525-32 pubmed
    ..These results indicate that the KDEL receptor participates in the ER stress response not only by its retrieval ability but also by modulating MAP kinase signaling, which may affect the outcomes of the mammalian ER stress response. ..
  31. Cancino J, Capalbo A, Di Campli A, Giannotta M, Rizzo R, Jung J, et al. Control systems of membrane transport at the interface between the endoplasmic reticulum and the Golgi. Dev Cell. 2014;30:280-94 pubmed publisher
    ..Thus, a Golgi-based control system maintains transport homeostasis through both signaling and transcriptional networks. ..
  32. Mei M, Zhai C, Li X, Zhou Y, Peng W, Ma L, et al. Characterization of aromatic residue-controlled protein retention in the endoplasmic reticulum of Saccharomyces cerevisiae. J Biol Chem. 2017;292:20707-20719 pubmed publisher
    ..found that the length, type of amino acid residue, and additional residues at positions -5 and -6 of the C-terminal HDEL motif all determined the retention of ERS in the yeast ER...
  33. Saudek V. Cystinosin, MPDU1, SWEETs and KDELR belong to a well-defined protein family with putative function of cargo receptors involved in vesicle trafficking. PLoS ONE. 2012;7:e30876 pubmed publisher
    ..searches in protein databases using endoplasmic reticulum lumen protein retaining receptors (KDEL, Erd2) as query reveal a large and diverse family of proteins with seven transmembrane helices and common topology and, ..
  34. Majoul I, Straub M, Hell S, Duden R, Söling H. KDEL-cargo regulates interactions between proteins involved in COPI vesicle traffic: measurements in living cells using FRET. Dev Cell. 2001;1:139-53 pubmed
    How the occupied KDEL receptor ERD2 is sorted into COPI vesicles for Golgi-to-ER transport is largely unknown...
  35. Ruggiero C, Fragassi G, Grossi M, Picciani B, Di Martino R, Capitani M, et al. A Golgi-based KDELR-dependent signalling pathway controls extracellular matrix degradation. Oncotarget. 2015;6:3375-93 pubmed
    ..This study furthers our understanding of the regulatory circuitry underlying invadopodia-dependent ECM degradation, a key phase in metastases formation and invasive growth. ..