Details for: CCL26

Gene ID: 10344

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: CCL26

Ensembl ID: ENSG00000006606

Description: C-C motif chemokine ligand 26

Cell Significance Landscape

Associated with

Significant Cells

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

  • stromal cell of ovary CL0002132
    CSI 1.57
    rCSI 4.31%
    PRS 99.75
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.15
    rCSI 3.33%
    PRS 99.59
  • pancreatic stellate cell CL0002410
    CSI 0.81
    rCSI 4.71%
    PRS 99.42

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.

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  • Node Color (Target Cell CSI, relative to current network):
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    • 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 [CCL26](/details-gene/10344) (C-C motif chemokine ligand 26) is a protein-coding gene that encodes a small, secreted cytokine belonging to the CC chemokine family. Also known as eotaxin-3, this protein functions as a potent chemoattractant, primarily for immune cells such as eosinophils, monocytes, and T cells, by binding to chemokine receptors CCR3 and CX3CR1 ([Link](https://doi.org/10.1074/jbc.274.39.27975), [Link](https://doi.org/10.4049/jimmunol.0904126)). Its primary roles are in cell-cell signaling, mediating chemotaxis, and contributing to inflammatory responses. **Overall**, expression data indicates that [CCL26](/details-gene/10344) is a significant marker in several non-hematopoietic cell types, including the [stromal cell of ovary](/details-cell/CL0002132), [microcirculation associated smooth muscle cell](/details-cell/CL0008035), and [pancreatic stellate cell](/details-cell/CL0002410), suggesting a role for these structural cells in orchestrating localized immune cell recruitment. ## Cellular Roles and Expression Landscape The expression profile of [CCL26](/details-gene/10344) highlights its role as a chemokine produced by tissue-resident, structural cells rather than by canonical immune cells. **Overall**, its most significant expression is observed in the [stromal cell of ovary](/details-cell/CL0002132) (CSI: 1.57), [microcirculation associated smooth muscle cell](/details-cell/CL0008035) (CSI: 1.15), and [pancreatic stellate cell](/details-cell/CL0002410) (CSI: 0.81). This pattern suggests that [CCL26](/details-gene/10344) is not a lineage marker for these cells but rather a functional effector molecule they secrete to communicate with the immune system. The high expression in these diverse stromal and smooth muscle backgrounds points to a conserved mechanism whereby structural tissues can initiate and shape inflammatory infiltrates in response to local cues or injury. This is consistent with early studies showing its expression in IL-4-stimulated vascular endothelial cells ([Link](https://pubmed.ncbi.nlm.nih.gov/10415065/)). ## Pathways and Molecular Function Functionally, [CCL26](/details-gene/10344) operates as an extracellular signaling molecule ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)) with potent `chemokine activity` ([GO:0008009](https://www.ebi.ac.uk/QuickGO/term/GO:0008009)). Its biological effects are mediated through the `chemokine-mediated signaling pathway` ([GO:0070098](https://www.ebi.ac.uk/QuickGO/term/GO:0070098)) upon binding to its cognate receptors. It is a well-established functional ligand for `CCR3 chemokine receptor binding` ([GO:0031728](https://www.ebi.ac.uk/QuickGO/term/GO:0031728)) and `CX3C chemokine receptor binding` ([GO:0031737](https://www.ebi.ac.uk/QuickGO/term/GO:0031737)). This interaction triggers intracellular signaling cascades that lead to `chemotaxis` ([GO:0006935](https://www.ebi.ac.uk/QuickGO/term/GO:0006935)), the directed migration of cells. The gene is specifically implicated in `eosinophil chemotaxis` ([GO:0048245](https://www.ebi.ac.uk/QuickGO/term/GO:0048245)), `monocyte chemotaxis` ([GO:0002548](https://www.ebi.ac.uk/QuickGO/term/GO:0002548)), and `T cell chemotaxis` ([GO:0010818](https://www.ebi.ac.uk/QuickGO/term/GO:0010818)), aligning with the expression of CCR3 and CX3CR1 on these immune cell populations. This functional profile solidifies the role of [CCL26](/details-gene/10344) as a key orchestrator of the `inflammatory response` ([GO:0006954](https://www.ebi.ac.uk/QuickGO/term/GO:0006954)) by recruiting specific leukocyte subsets to sites of its expression, such as the ovary, pancreas, and microvasculature. ## Research Directions The expression of [CCL26](/details-gene/10344) in tissue-resident stromal cells, combined with its potent chemoattractant properties, opens several avenues for investigation into its role in tissue-specific inflammation and pathology. **Proposed Hypotheses:** 1. Given its high significance in [pancreatic stellate cell](/details-cell/CL0002410), [CCL26](/details-gene/10344) likely functions as a critical mediator in the pathogenesis of pancreatitis and pancreatic fibrosis by recruiting CCR3- and CX3CR1-expressing monocytes and eosinophils, which contribute to tissue damage and remodeling. 2. The prominent expression of [CCL26](/details-gene/10344) in the [stromal cell of ovary](/details-cell/CL0002132) suggests it plays a role in regulating the cyclical inflammation associated with the normal ovarian cycle or contributes to the inflammatory microenvironment in pathologies like ovarian cancer or endometriosis. **Experimental Approach:** To test the first hypothesis regarding the role of [CCL26](/details-gene/10344) in pancreatic pathology, a compelling experiment would involve a mouse model of chronic pancreatitis. `Ccl26` knockout mice and wild-type controls could be subjected to repeated cerulein injections to induce chronic inflammation and fibrosis. The extent of disease could be assessed by measuring pancreatic histology (for fibrosis and acinar cell loss), quantifying the infiltration of specific immune cell populations (monocytes/macrophages, eosinophils) via flow cytometry and immunohistochemistry, and analyzing the expression of pro-fibrotic genes (e.g., *Col1a1*, *Acta2*) in pancreatic tissue using qPCR. A significant reduction in immune infiltration and fibrosis in the knockout mice would confirm [CCL26](/details-gene/10344) as a key driver of the disease. **Therapeutic Potential:** As a secreted protein that orchestrates pathological inflammation, [CCL26](/details-gene/10344) represents an attractive therapeutic target. The strategy would focus on **inhibition** to block the recruitment of damaging inflammatory cells. This could be particularly relevant for eosinophil-driven diseases such as eosinophilic esophagitis, asthma, or atopic dermatitis, as well as diseases involving monocyte infiltration like pancreatitis or certain fibrotic conditions. Potential therapeutic modalities include monoclonal antibodies designed to neutralize circulating [CCL26](/details-gene/10344) or small molecule antagonists that block its binding to its receptors, CCR3 and CX3CR1. Such an approach could offer a targeted anti-inflammatory therapy with potentially fewer side effects than broad-spectrum immunosuppressants.

Genular Protein ID: 2384088005

Symbol: CCL26_HUMAN

Name: C-C motif chemokine 26

UniProtKB Accession Codes:

Q9Y258 A0N0Q5 Q52LV8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 EMBL 12 Ensembl 2 EvolutionaryTrace 1 GO 20 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 2 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10373330

Title: Molecular cloning and characterization of a novel human CC chemokine, SCYA26.

PubMed ID: 10373330

DOI: 10.1006/geno.1999.5837

PubMed ID: 10415065

Title: A novel human CC chemokine, eotaxin-3, which is expressed in IL-4-stimulated vascular endothelial cells, exhibits potent activity toward eosinophils.

PubMed ID: 10415065

PubMed ID: 10488147

Title: Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3.

PubMed ID: 10488147

DOI: 10.1074/jbc.274.39.27975

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

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: 11425309

Title: NMR solution structure and backbone dynamics of the CC chemokine eotaxin-3.

PubMed ID: 11425309

DOI: 10.1021/bi010252s

PubMed ID: 20974991

Title: Eotaxin-3/CC chemokine ligand 26 is a functional ligand for CX3CR1.

PubMed ID: 20974991

DOI: 10.4049/jimmunol.0904126

Sequence Information:

  • Length: 94
  • Mass: 10648
  • Checksum: 8525B1E4BDD39A5F
  • Sequence:
    • MMGLSLASAV LLASLLSLHL GTATRGSDIS KTCCFQYSHK PLPWTWVRSY EFTSNSCSQR 
AVIFTTKRGK KVCTHPRKKW VQKYISLLKT PKQL