Details for: KDELR3

Gene ID: 11015

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: KDELR3

Ensembl ID: ENSG00000100196

Description: KDEL endoplasmic reticulum protein retention receptor 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • bronchus fibroblast of lung CL2000093
    CSI 8.4
    rCSI 6.83%
    PRS 90.93
  • myofibroblast cell CL0000186
    CSI 7.44
    rCSI 10.31%
    PRS 88.54
  • ependymal cell CL0000065
    CSI 6.74
    rCSI 13.67%
    PRS 74.95
  • goblet cell CL0000160
    CSI 4.08
    rCSI 3.85%
    PRS 89.57
  • mucus secreting cell CL0000319
    CSI 3.68
    rCSI 5.84%
    PRS 95.23
  • intestine goblet cell CL0019031
    CSI 3.62
    rCSI 3.21%
    PRS 89.28
  • neural crest cell CL0011012
    CSI 3.45
    rCSI 2.73%
    PRS 85.16
  • alveolar adventitial fibroblast CL4028006
    CSI 3.26
    rCSI 5.16%
    PRS 92.42
  • extravillous trophoblast CL0008036
    CSI 3.2
    rCSI 3.96%
    PRS 90.02
  • skin fibroblast CL0002620
    CSI 3.02
    rCSI 2.61%
    PRS 91.05
  • intestinal epithelial cell CL0002563
    CSI 2.91
    rCSI 3.04%
    PRS 89.34
  • mesodermal cell CL0000222
    CSI 2.83
    rCSI 3.4%
    PRS 90.46
  • epithelial cell of lung CL0000082
    CSI 2.81
    rCSI 2.33%
    PRS 92.38
  • tracheobronchial serous cell CL0019001
    CSI 2.79
    rCSI 12.07%
    PRS 93.43
  • stem cell CL0000034
    CSI 2.51
    rCSI 2.42%
    PRS 87.79
  • mucous neck cell CL0000651
    CSI 2.42
    rCSI 3.49%
    PRS 93.87
  • ciliated epithelial cell CL0000067
    CSI 2.39
    rCSI 2.1%
    PRS 83.38
  • foveolar cell of stomach CL0002179
    CSI 1.91
    rCSI 4.06%
    PRS 93.35
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.87
    rCSI 1.8%
    PRS 90.15
  • mesenchymal cell CL0008019
    CSI 1.64
    rCSI 4.17%
    PRS 86.97
  • chondrocyte CL0000138
    CSI 1.51
    rCSI 2.4%
    PRS 87.36
  • bronchial goblet cell CL1000312
    CSI 1.25
    rCSI 5.01%
    PRS 94.24
  • fibroblast of breast CL4006000
    CSI 1.25
    rCSI 5.27%
    PRS 93.15
  • GABAergic neuron CL0000617
    CSI 1.19
    rCSI 3.99%
    PRS 79.07
  • podocyte CL0000653
    CSI 1.09
    rCSI 4.85%
    PRS 91.81
  • colon goblet cell CL0009039
    CSI 1.01
    rCSI 2.39%
    PRS 93.05
  • pancreatic stellate cell CL0002410
    CSI 0.69
    rCSI 4.03%
    PRS 92.92
  • respiratory goblet cell CL0002370
    CSI 0.66
    rCSI 7.15%
    PRS 93.83
  • osteoblast CL0000062
    CSI 0.33
    rCSI 8.27%
    PRS 95.57

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [KDELR3](/details-gene/11015), or KDEL Endoplasmic Reticulum Protein Retention Receptor 3, is a transmembrane protein that plays a fundamental role in intracellular protein trafficking. As a member of the KDEL receptor family, its primary function is to recognize and retrieve soluble endoplasmic reticulum (ER) resident proteins that have escaped to the Golgi apparatus, ensuring their return to the ER. This process is critical for maintaining ER homeostasis and function. **Overall**, expression data indicates that [KDELR3](/details-gene/11015) is particularly significant in cells with high secretory and protein processing demands, such as various types of fibroblasts, secretory epithelial cells like [goblet cell](/details-cell/CL0000160)s, and [ependymal cell](/details-cell/CL0000065)s. ## Cellular Roles and Expression Landscape The expression profile of [KDELR3](/details-gene/11015) highlights its importance in cells responsible for secretion and the production of extracellular matrix components. **Overall**, it shows the highest significance in mesenchymal and secretory cell types. - **Mesenchymal and Structural Cells:** The gene is a top marker in several fibroblast populations, including [bronchus fibroblast of lung](/details-cell/CL2000093) (CSI: 8.40), [myofibroblast cell](/details-cell/CL0000186) (CSI: 7.44), [alveolar adventitial fibroblast](/details-cell/CL4028006) (CSI: 3.26), and [skin fibroblast](/details-cell/CL0002620) (CSI: 3.02). This strong association suggests a critical role in managing the high volume of protein synthesis and secretion required for building and maintaining the extracellular matrix. - **Secretory Epithelial and Glial Cells:** [KDELR3](/details-gene/11015) is also highly significant in specialized secretory cells, such as [goblet cell](/details-cell/CL0000160)s (CSI: 4.08), [mucus secreting cell](/details-cell/CL0000319)s (CSI: 3.68), and [intestine goblet cell](/details-cell/CL0019031)s (CSI: 3.62), consistent with its function in handling the heavy protein load of mucus production. Its high significance in [ependymal cell](/details-cell/CL0000065)s (CSI: 6.74), which line the ventricles of the brain and are involved in cerebrospinal fluid production, further underscores its importance in cells with specialized secretory functions. The elevated expression in these distinct cell lineages points to a ubiquitous and essential role for [KDELR3](/details-gene/11015) in the quality control and efficiency of the secretory pathway, particularly in cells that are professionally engaged in protein export. ## Pathways and Molecular Function The functional annotations for [KDELR3](/details-gene/11015) confirm its central role in the ER-Golgi trafficking system. Its molecular function is defined by [Kdel sequence binding](https://www.ebi.ac.uk/QuickGO/term/GO:0005046) and [Er retention sequence binding](https://www.ebi.ac.uk/QuickGO/term/GO:0046923), which are the key recognition steps for retrieving ER-resident proteins. This function has been shown to be specific among the three mammalian KDEL receptors ([Link](https://doi.org/10.1083/jcb.200705180)). This binding activity enables its primary biological process: [Retrograde vesicle-mediated transport, golgi to endoplasmic reticulum](https://www.ebi.ac.uk/QuickGO/term/GO:0006890). This is further detailed in Reactome pathways such as [Copi-dependent golgi-to-er retrograde traffic](https://reactome.org/content/detail/R-HSA-6811434) and [Intra-golgi and retrograde golgi-to-er traffic](https://reactome.org/content/detail/R-HSA-6811442). [KDELR3](/details-gene/11015) is an integral component of the [Copi-coated vesicle membrane](https://www.ebi.ac.uk/QuickGO/term/GO:0030663), which facilitates this transport. Furthermore, its involvement in pathways like the [Unfolded protein response (upr)](https://reactome.org/content/detail/R-HSA-381119) and [Cellular responses to stress](https://reactome.org/content/detail/R-HSA-2262752) suggests that its function is crucial for mitigating ER stress, a condition that can arise from high rates of protein synthesis. This is highly consistent with its prominent expression in professionally secretory cells. ## Research Directions The specific expression pattern and core biological function of [KDELR3](/details-gene/11015) suggest potential involvement in pathologies characterized by dysregulated protein secretion. **Proposed Hypotheses:** 1. Given its high significance in multiple fibroblast types, dysregulation of [KDELR3](/details-gene/11015) may contribute to fibrotic diseases, such as idiopathic pulmonary fibrosis or scleroderma. An overload or malfunction of the KDELR3-mediated retrieval pathway could lead to ER stress and subsequent activation of pro-fibrotic pathways, resulting in excessive deposition of extracellular matrix proteins. 2. The high significance of [KDELR3](/details-gene/11015) in mucus-producing cells suggests that altered [KDELR3](/details-gene/11015) expression or function could be a factor in diseases of mucus hypersecretion, such as chronic obstructive pulmonary disease (COPD) or certain types of mucinous adenocarcinomas. Impaired ER-Golgi trafficking could affect the proper folding and processing of mucin proteins, contributing to pathology. **Experimental Approach:** To test the hypothesis regarding its role in fibrosis (Hypothesis 1), a compelling experiment would be to investigate the consequence of its loss of function in a relevant cell model. One could use CRISPR-Cas9 to knock out [KDELR3](/details-gene/11015) in primary human lung fibroblasts ([bronchus fibroblast of lung](/details-cell/CL2000093)). These knockout and control cells could then be stimulated with a pro-fibrotic cytokine, such as TGF-beta. The impact on fibrosis-related endpoints could be assessed by measuring the secretion of collagen and fibronectin via ELISA or Western blot, and by analyzing the expression of fibrotic marker genes (e.g., *ACTA2*, *COL1A1*) using RT-qPCR. This would directly test whether [KDELR3](/details-gene/11015) is required for the pathological secretion of ECM proteins. **Therapeutic Potential:** As an intracellular trafficking receptor, [KDELR3](/details-gene/11015) presents a challenging but potentially valuable therapeutic target. Direct inhibition might be beneficial in diseases driven by excessive protein secretion, such as fibrosis or mucinous cancers. However, because it is a fundamental component of cellular machinery, systemic inhibition would likely cause significant toxicity. A more targeted approach, such as developing small molecules that selectively disrupt the interaction of [KDELR3](/details-gene/11015) with specific pro-pathogenic cargo proteins, could offer a more viable therapeutic strategy with a better safety profile.

Genular Protein ID: 1529403035

Symbol: ERD23_HUMAN

Name: ER lumen protein-retaining receptor 3

UniProtKB Accession Codes:

O43731 A8K7T7 B8ZZ26 O95557 Q4V750 Q4V767 Q53FP4 Q53GK1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 13 Ensembl 2 ExpressionAtlas 1 GO 12 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 3 RefSeq 2 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12529303

Title: Reevaluating human gene annotation: a second-generation analysis of chromosome 22.

PubMed ID: 12529303

DOI: 10.1101/gr.695703

PubMed ID: 15461802

Title: A genome annotation-driven approach to cloning the human ORFeome.

PubMed ID: 15461802

DOI: 10.1186/gb-2004-5-10-r84

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18086916

Title: A molecular specificity code for the three mammalian KDEL receptors.

PubMed ID: 18086916

DOI: 10.1083/jcb.200705180

Sequence Information:

  • Length: 214
  • Mass: 25027
  • Checksum: ED5F7D303390B314
  • Sequence:
    • MNVFRILGDL SHLLAMILLL GKIWRSKCCK GISGKSQILF ALVFTTRYLD LFTNFISIYN 
TVMKVVFLLC AYVTVYMIYG KFRKTFDSEN DTFRLEFLLV PVIGLSFLEN YSFTLLEILW 
TFSIYLESVA ILPQLFMISK TGEAETITTH YLFFLGLYRA LYLANWIRRY QTENFYDQIA 
VVSGVVQTIF YCDFFYLYVT KVLKGKKLSL PMPI