Details for: CXCL17

Gene ID: 284340

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: CXCL17

Ensembl ID: ENSG00000189377

Description: C-X-C motif chemokine ligand 17

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • epithelial cell of lower respiratory tract CL0002632
    CSI 38.52
    rCSI 29.86%
    PRS 96.23
  • nasal mucosa goblet cell CL0002480
    CSI 26.97
    rCSI 31.27%
    PRS 94.35
  • mucous neck cell CL0000651
    CSI 21.27
    rCSI 30.66%
    PRS 96.2
  • club cell CL0000158
    CSI 20.31
    rCSI 29.75%
    PRS 91.8
  • respiratory suprabasal cell CL4033048
    CSI 19.66
    rCSI 25.22%
    PRS 95.58
  • tracheal goblet cell CL1000329
    CSI 18.71
    rCSI 40.85%
    PRS 95.51
  • conjunctival epithelial cell CL1000432
    CSI 18.54
    rCSI 28.31%
    PRS 93.75
  • mucus secreting cell CL0000319
    CSI 16.87
    rCSI 26.79%
    PRS 97.16
  • duct epithelial cell CL0000068
    CSI 15.33
    rCSI 22.42%
    PRS 96.79
  • acinar cell CL0000622
    CSI 14.5
    rCSI 21.27%
    PRS 97.41
  • multi-ciliated epithelial cell CL0005012
    CSI 14.47
    rCSI 14.45%
    PRS 90.18
  • epithelial cell of lung CL0000082
    CSI 13.76
    rCSI 11.41%
    PRS 95.51
  • ependymal cell CL0000065
    CSI 12.79
    rCSI 25.95%
    PRS 80.74
  • secretory cell CL0000151
    CSI 12.79
    rCSI 13.34%
    PRS 93.88
  • bronchial goblet cell CL1000312
    CSI 11.77
    rCSI 47.04%
    PRS 96.47
  • pulmonary alveolar type 2 cell CL0002063
    CSI 11.54
    rCSI 17.9%
    PRS 94.87
  • brush cell of tracheobronchial tree CL0002075
    CSI 11.49
    rCSI 34.08%
    PRS 97.65
  • lung ciliated cell CL1000271
    CSI 11.31
    rCSI 13.08%
    PRS 90.6
  • respiratory basal cell CL0002633
    CSI 11.26
    rCSI 11.67%
    PRS 95.66
  • ciliated cell CL0000064
    CSI 11.22
    rCSI 18.18%
    PRS 89.43
  • fallopian tube secretory epithelial cell CL4030006
    CSI 10.72
    rCSI 10.31%
    PRS 93.44
  • foveolar cell of stomach CL0002179
    CSI 10.35
    rCSI 22.03%
    PRS 95.75
  • squamous epithelial cell CL0000076
    CSI 10.22
    rCSI 24.26%
    PRS 91.34
  • tracheobronchial serous cell CL0019001
    CSI 10
    rCSI 43.23%
    PRS 96.01
  • pancreatic acinar cell CL0002064
    CSI 9.96
    rCSI 13.24%
    PRS 96.24
  • adipocyte CL0000136
    CSI 9.82
    rCSI 12.61%
    PRS 88.56
  • ciliated epithelial cell CL0000067
    CSI 9.75
    rCSI 8.57%
    PRS 88.04
  • dendritic cell CL0000451
    CSI 8.37
    rCSI 10.31%
    PRS 93.78
  • pulmonary ionocyte CL0017000
    CSI 8.23
    rCSI 10.01%
    PRS 96.52
  • ionocyte CL0005006
    CSI 7.71
    rCSI 8.27%
    PRS 95.41
  • lung secretory cell CL1000272
    CSI 7.32
    rCSI 18.13%
    PRS 95.81
  • serous secreting cell CL0000313
    CSI 7.17
    rCSI 36.28%
    PRS 96.38
  • goblet cell CL0000160
    CSI 6.69
    rCSI 6.32%
    PRS 92.75
  • enteroendocrine cell CL0000164
    CSI 6.52
    rCSI 8.91%
    PRS 92.74
  • respiratory hillock cell CL4030023
    CSI 6.49
    rCSI 11.58%
    PRS 96.53
  • corneal epithelial cell CL0000575
    CSI 6.25
    rCSI 17.87%
    PRS 95.12
  • deuterosomal cell CL4033044
    CSI 6.24
    rCSI 21.11%
    PRS 89.45
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 5.4
    rCSI 12.31%
    PRS 88.72
  • pulmonary alveolar type 1 cell CL0002062
    CSI 4.96
    rCSI 28.62%
    PRS 92.61
  • peptic cell CL0000155
    CSI 3.91
    rCSI 38.47%
    PRS 96.8
  • respiratory goblet cell CL0002370
    CSI 3.88
    rCSI 42.18%
    PRS 96.29
  • basal cell of epithelium of trachea CL1000348
    CSI 3.61
    rCSI 25.5%
    PRS 94.9
  • luminal cell of prostate epithelium CL0002340
    CSI 3.52
    rCSI 18.95%
    PRS 96.79
  • airway submucosal gland duct basal cell CL4033024
    CSI 3.12
    rCSI 19.93%
    PRS 95.2
  • tracheobronchial goblet cell CL0019003
    CSI 2.79
    rCSI 44.9%
    PRS 94.36
  • mammary gland epithelial cell CL0002327
    CSI 2.71
    rCSI 9.52%
    PRS 96.89
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.28
    rCSI 8.2%
    PRS 84.38
  • neutrophil CL0000775
    CSI 2.19
    rCSI 12.26%
    PRS 92.08
  • parietal cell CL0000162
    CSI 2.04
    rCSI 17.59%
    PRS 96.51
  • glandular epithelial cell CL0000150
    CSI 1.86
    rCSI 4.9%
    PRS 98.23
  • lung goblet cell CL1000143
    CSI 1.8
    rCSI 20.16%
    PRS 96.5
  • stratified epithelial cell CL0000079
    CSI 1.63
    rCSI 10.07%
    PRS 95.79
  • epithelial cell of urethra CL1000296
    CSI 1.3
    rCSI 32.81%
    PRS 95.76
  • epithelial cell of esophagus CL0002252
    CSI 1.27
    rCSI 12.53%
    PRS 92.59
  • serous secreting cell of bronchus submucosal gland CL4033005
    CSI 1.18
    rCSI 6.73%
    PRS 94.78
  • acinar cell of salivary gland CL0002623
    CSI 0.18
    rCSI 4.11%
    PRS 97.36

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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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 [CXCL17](/details-gene/284340), or C-X-C motif chemokine ligand 17, is a secreted protein that functions as a chemokine. **Overall**, expression data reveals that [CXCL17](/details-gene/284340) is a highly significant marker for various mucosal and glandular epithelial cells, particularly those of the respiratory tract such as [epithelial cell of lower respiratory tract](/details-cell/CL0002632) and [nasal mucosa goblet cell](/details-cell/CL0002480). Its established roles in macrophage and monocyte chemotaxis, angiogenesis, and the regulation of inflammation suggest it is a key signaling molecule in mucosal immunity, tissue homeostasis, and pathological processes like tumor development ([Link](https://doi.org/10.1016/j.bbrc.2006.08.194)). ## Cellular Roles and Expression Landscape The expression profile of [CXCL17](/details-gene/284340) strongly points to a primary role at the body's barrier surfaces. **Overall**, it is most significantly expressed in a variety of secretory and epithelial cell types responsible for producing mucus and other protective fluids. The highest significance scores are observed in cells of the respiratory system, including [epithelial cell of lower respiratory tract](/details-cell/CL0002632) (CSI: 38.52), [nasal mucosa goblet cell](/details-cell/CL0002480) (CSI: 26.97), [club cell](/details-cell/CL0000158) (CSI: 20.31), and [tracheal goblet cell](/details-cell/CL1000329) (CSI: 18.71). This pattern extends to other mucosal and glandular tissues, with high significance in [mucous neck cell](/details-cell/CL0000651) of the stomach, [conjunctival epithelial cell](/details-cell/CL1000432) of the eye, and various [secretory cell](/details-cell/CL0000151) types like [acinar cell](/details-cell/CL0000622). This localization suggests [CXCL17](/details-gene/284340) functions as a sentinel chemokine, constitutively expressed at mucosal interfaces to orchestrate immune surveillance and maintain tissue integrity. An interesting observation is its notable expression in [ependymal cell](/details-cell/CL0000065), which line the ventricles of the brain, implying a potential role in central nervous system homeostasis or immune trafficking. ## Pathways and Molecular Function Functionally, [CXCL17](/details-gene/284340) is annotated as an extracellular protein ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)) involved in several key biological processes. Its primary role as a chemokine is supported by its involvement in the positive regulation of [macrophage chemotaxis](/details-cell/CL0000235) ([GO:0010759](https://www.ebi.ac.uk/QuickGO/term/GO:0010759)) and [monocyte chemotaxis](/details-cell/CL0000576) ([GO:0090026](https://www.ebi.ac.uk/QuickGO/term/GO:0090026)). Research has identified its cognate receptor as GPR35, also known as CXCR8, confirming its role in directing myeloid cell migration ([Link](https://doi.org/10.4049/jimmunol.1401704)). Beyond immune cell trafficking, [CXCL17](/details-gene/284340) is implicated in tissue modeling and inflammation. It participates in [angiogenesis](/details-cell/GO:0001525) ([GO:0001525](https://www.ebi.ac.uk/QuickGO/term/GO:0001525)) and positively regulates the production of vascular endothelial growth factor ([GO:0010575](https://www.ebi.ac.uk/QuickGO/term/GO:0010575)), processes critical for both wound healing and tumor growth ([Link](https://doi.org/10.1152/ajpendo.00083.2012)). Furthermore, its annotation for the [negative regulation of inflammatory response](/details-cell/GO:0050728) ([GO:0050728](https://www.ebi.ac.uk/QuickGO/term/GO:0050728)) suggests a complex, dual function where it may help resolve inflammation under certain conditions while promoting it in others. ## Research Directions The dual role of [CXCL17](/details-gene/284340) in both homeostatic immune surveillance at mucosal barriers and in pathological processes like tumor progression presents several compelling avenues for future research. **Proposed Hypotheses:** 1. Given its high expression by mucosal epithelia and its chemoattractant properties for monocytes and macrophages, it is hypothesized that [CXCL17](/details-gene/284340) is a key factor in establishing and maintaining the resident myeloid cell populations in tissues like the lung and gut, acting as a homeostatic signal that can be rapidly modulated during infection or injury. 2. Based on reports that [CXCL17](/details-gene/284340) promotes tumor growth ([Link](https://doi.org/10.1016/j.bbrc.2006.08.194)) and angiogenesis, a second hypothesis is that cancer cells, particularly those of epithelial origin (e.g., lung adenocarcinoma), hijack [CXCL17](/details-gene/284340) expression to recruit and polarize tumor-associated macrophages (TAMs) towards a pro-angiogenic and immunosuppressive phenotype, thereby creating a favorable tumor microenvironment. **Experimental Approach:** To test the second hypothesis, one could employ a syngeneic mouse model of lung cancer using tumor cells (e.g., Lewis Lung Carcinoma) engineered with a CRISPR-Cas9 knockout of *Cxcl17*. Following implantation in immunocompetent mice, tumor growth rates, metastasis, and microvessel density (via CD31 immunohistochemistry) would be compared between tumors expressing and lacking *Cxcl17*. Concurrently, the immune infiltrate of the tumors would be analyzed by single-cell RNA sequencing to determine if the absence of *Cxcl17* alters the abundance, spatial localization, or transcriptional state of specific macrophage and monocyte subsets. **Therapeutic Potential:** As a secreted protein, [CXCL17](/details-gene/284340) is an accessible therapeutic target. Its reported role in promoting tumor growth makes it a candidate for therapeutic **inhibition**. The development of a neutralizing monoclonal antibody against [CXCL17](/details-gene/284340) or a small molecule antagonist for its receptor, GPR35/CXCR8, could represent a novel anti-cancer strategy. Such a therapy might function by reducing tumor-associated angiogenesis and by altering the immune microenvironment to be less permissive to tumor growth, potentially synergizing with existing checkpoint inhibitor immunotherapies.

Genular Protein ID: 2799670511

Symbol: CXL17_HUMAN

Name: C-X-C motif chemokine 17

UniProtKB Accession Codes:

Q6UXB2 A8KAC0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 9 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 16989774

Title: VCC-1, a novel chemokine, promotes tumor growth.

PubMed ID: 16989774

DOI: 10.1016/j.bbrc.2006.08.194

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 25946035

Title: Human basal tear peptidome characterization by CID, HCD, and ETD followed by in silico and in vitro analyses for antimicrobial peptide identification.

PubMed ID: 25946035

DOI: 10.1021/acs.jproteome.5b00179

PubMed ID: 16455961

Title: Novel human dendritic cell- and monocyte-attracting chemokine-like protein identified by fold recognition methods.

PubMed ID: 16455961

DOI: 10.4049/jimmunol.176.4.2069

PubMed ID: 17307946

Title: Broad up-regulation of innate defense factors during acute cholera.

PubMed ID: 17307946

DOI: 10.1128/iai.01900-06

PubMed ID: 23115081

Title: CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor.

PubMed ID: 23115081

DOI: 10.1152/ajpendo.00083.2012

PubMed ID: 25411203

Title: GPR35/CXCR8 is the receptor of the mucosal chemokine CXCL17.

PubMed ID: 25411203

DOI: 10.4049/jimmunol.1401704

Sequence Information:

  • Length: 119
  • Mass: 13819
  • Checksum: F2D2FD686E47CC9B
  • Sequence:
    • MKVLISSLLL LLPLMLMSMV SSSLNPGVAR GHRDRGQASR RWLQEGGQEC ECKDWFLRAP 
RRKFMTVSGL PKKQCPCDHF KGNVKKTRHQ RHHRKPNKHS RACQQFLKQC QLRSFALPL