Details for: CX3CL1

Gene ID: 6376

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: CX3CL1

Ensembl ID: ENSG00000006210

Description: C-X3-C motif chemokine ligand 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • pulmonary capillary endothelial cell CL4028001
    CSI 8.89
    rCSI 16.95%
    PRS 94.35
  • epithelial cell of lung CL0000082
    CSI 5.64
    rCSI 4.67%
    PRS 89.25
  • acinar cell CL0000622
    CSI 4.89
    rCSI 7.17%
    PRS 94.05
  • luminal epithelial cell of mammary gland CL0002326
    CSI 4.28
    rCSI 7.78%
    PRS 93.96
  • multi-ciliated epithelial cell CL0005012
    CSI 3.52
    rCSI 3.52%
    PRS 82.45
  • secretory cell CL0000151
    CSI 3.37
    rCSI 3.52%
    PRS 87.03
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.3
    rCSI 2.56%
    PRS 91.12
  • duct epithelial cell CL0000068
    CSI 3.19
    rCSI 4.66%
    PRS 91.87
  • respiratory suprabasal cell CL4033048
    CSI 2.84
    rCSI 3.64%
    PRS 90.12
  • pulmonary artery endothelial cell CL1001568
    CSI 2.55
    rCSI 3.46%
    PRS 93.3
  • blood vessel endothelial cell CL0000071
    CSI 2.54
    rCSI 5.27%
    PRS 86.08
  • myofibroblast cell CL0000186
    CSI 2.44
    rCSI 3.38%
    PRS 84.74
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.42
    rCSI 6.13%
    PRS 80.96
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.41
    rCSI 3.41%
    PRS 85.57
  • cerebral cortex endothelial cell CL1001602
    CSI 2.4
    rCSI 4.15%
    PRS 81.98
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.39
    rCSI 8.6%
    PRS 71.72
  • inhibitory interneuron CL0000498
    CSI 2.3
    rCSI 5.31%
    PRS 78.37
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.23
    rCSI 3.56%
    PRS 91.07
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.1
    rCSI 2.51%
    PRS 73.86
  • respiratory basal cell CL0002633
    CSI 1.91
    rCSI 1.98%
    PRS 90.21
  • club cell CL0000158
    CSI 1.79
    rCSI 2.63%
    PRS 83.44
  • cardiac endothelial cell CL0010008
    CSI 1.77
    rCSI 7.15%
    PRS 88.69
  • melanocyte of skin CL1000458
    CSI 1.76
    rCSI 2.4%
    PRS 57.69
  • basal cell of prostate epithelium CL0002341
    CSI 1.71
    rCSI 4.95%
    PRS 91.64
  • cerebral cortex neuron CL0010012
    CSI 1.71
    rCSI 6.96%
    PRS 80.74
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.69
    rCSI 2.1%
    PRS 71.52
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.65
    rCSI 2.12%
    PRS 74.84
  • lung microvascular endothelial cell CL2000016
    CSI 1.55
    rCSI 29.91%
    PRS 93.14
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.54
    rCSI 1.87%
    PRS 68.76
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.54
    rCSI 2.47%
    PRS 74.88
  • mammary gland epithelial cell CL0002327
    CSI 1.46
    rCSI 5.12%
    PRS 92.8
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.36
    rCSI 3.93%
    PRS 87.39
  • vasa recta ascending limb cell CL1001131
    CSI 1.32
    rCSI 5.98%
    PRS 92.83
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.31
    rCSI 4.09%
    PRS 77.08
  • pancreatic ductal cell CL0002079
    CSI 1.23
    rCSI 2.39%
    PRS 89.93
  • tracheal goblet cell CL1000329
    CSI 1.18
    rCSI 2.58%
    PRS 91.29
  • luminal cell of prostate epithelium CL0002340
    CSI 1.08
    rCSI 5.81%
    PRS 92.78
  • medium spiny neuron CL1001474
    CSI 0.93
    rCSI 7.99%
    PRS 79.11
  • endothelial cell of vascular tree CL0002139
    CSI 0.9
    rCSI 4.91%
    PRS 84.8
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.87
    rCSI 2.12%
    PRS 71.49
  • dopaminergic neuron CL0000700
    CSI 0.84
    rCSI 4.75%
    PRS 76.76
  • vasa recta descending limb cell CL1001285
    CSI 0.84
    rCSI 6.68%
    PRS 92.92
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.82
    rCSI 3.11%
    PRS 74.01
  • collagen secreting cell CL0000667
    CSI 0.8
    rCSI 4.6%
    PRS 91.84
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.79
    rCSI 2.46%
    PRS 75.18
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 0.76
    rCSI 1.74%
    PRS 81.23
  • basal cell of epithelium of trachea CL1000348
    CSI 0.54
    rCSI 3.82%
    PRS 89.85
  • direct pathway medium spiny neuron CL4023026
    CSI 0.52
    rCSI 12.44%
    PRS 71.31
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.51
    rCSI 12.22%
    PRS 71.73
  • vein endothelial cell of respiratory system CL4033008
    CSI 0.43
    rCSI 2.95%
    PRS 91.94
  • prostate gland microvascular endothelial cell CL2000059
    CSI 0.39
    rCSI 9.43%
    PRS 92.52
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.38
    rCSI 2.22%
    PRS 74.23
  • respiratory goblet cell CL0002370
    CSI 0.37
    rCSI 4.05%
    PRS 91.94

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 [CX3CL1](/details-gene/6376) (C-X3-C motif chemokine ligand 1), also known as fractalkine, is a unique member of the chemokine family characterized by a CX3C motif. It is a type I transmembrane protein that can function in both a membrane-anchored form, mediating cell adhesion, and a proteolytically cleaved soluble form, acting as a potent chemoattractant for leukocytes expressing its receptor, CX3CR1 ([Link](https://doi.org/10.1038/42491)). **Overall**, expression data reveals that [CX3CL1](/details-gene/6376) is most significantly expressed in endothelial and epithelial cell populations, particularly within the pulmonary, renal, and cerebral vasculature, suggesting a critical role in immune surveillance and leukocyte trafficking at tissue barriers. Its dual function as an adhesion molecule and a chemoattractant underlies its involvement in inflammatory responses, angiogenesis, and neuronal-microglial communication. ## Cellular Roles and Expression Landscape The expression profile of [CX3CL1](/details-gene/6376) highlights its prominent role at the interface between the circulatory system and various tissues. **Overall**, the gene shows the highest significance in endothelial cells, including [pulmonary capillary endothelial cell](/details-cell/CL4028001) (CSI: 8.89), [pulmonary artery endothelial cell](/details-cell/CL1001568) (CSI: 2.55), general [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 2.54), and [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 2.40). This strong and widespread endothelial expression is consistent with its established function in mediating the capture and firm adhesion of leukocytes under physiological flow conditions ([Link](https://doi.org/10.1084/jem.188.8.1413)). In addition to its endothelial signature, [CX3CL1](/details-gene/6376) is also a significant marker for various epithelial cell types. It is highly expressed in [epithelial cell of lung](/details-cell/CL0000082) (CSI: 5.64), [acinar cell](/details-cell/CL0000622) (CSI: 4.89), [luminal epithelial cell of mammary gland](/details-cell/CL0002326) (CSI: 4.28), and specialized kidney epithelial cells like [kidney connecting tubule epithelial cell](/details-cell/CL1000768) (CSI: 2.42). This pattern suggests that [CX3CL1](/details-gene/6376) plays a key role in orchestrating immune responses directly at epithelial barriers, which are often the first line of defense against pathogens. The expression in myofibroblasts and secretory cells further points to its involvement in tissue remodeling and wound healing. ## Pathways and Molecular Function The functional annotations for [CX3CL1](/details-gene/6376) confirm its identity as a key signaling molecule in the immune system. Its molecular function is dominated by [chemokine activity](/details-go/GO:0008009) and specific binding to the [CX3C chemokine receptor](/details-go/GO:0031737) (CX3CR1), which triggers downstream signaling events. Reactome pathways detail this process, showing involvement in [GPCR ligand binding](/details-go/R-HSA-500792) and subsequent [G alpha (i) signalling events](/details-go/R-HSA-418594). [CX3CL1](/details-gene/6376) also exhibits [integrin binding](/details-go/GO:0005178) capacity, allowing it to act as a coreceptor that enhances cell adhesion independent of its primary chemokine receptor ([Link](https://doi.org/10.4049/jimmunol.1200889)). Biologically, [CX3CL1](/details-gene/6376) is implicated in a wide array of processes centered on immunity and cellular communication. It is a central player in [chemokine-mediated signaling pathways](/details-go/GO:0070098) that drive [leukocyte chemotaxis](/details-go/GO:0030595), including the specific migration of [macrophages](/details-go/GO:0048246), [neutrophils](/details-go/GO:0030593), and [lymphocytes](/details-go/GO:0048247). This aligns perfectly with its expression in endothelial cells lining blood vessels, where it serves to recruit immune cells to sites of inflammation. Beyond general immunity, [CX3CL1](/details-gene/6376) has specialized roles, including the regulation of [microglial cell activation](/details-go/GO:0001774) and [synapse pruning](/details-go/GO:0098883) in the central nervous system, and involvement in [angiogenesis involved in wound healing](/details-go/GO:0060055). This diverse functionality underscores its importance as a pleiotropic signaling molecule. ## Research Directions The high and specific expression of [CX3CL1](/details-gene/6376) on endothelial and epithelial cells, coupled with its potent chemoattractant and adhesive functions, presents several avenues for future research into its role in health and disease. **Proposed Hypotheses:** 1. Given its top-ranking significance in [pulmonary capillary endothelial cell](/details-cell/CL4028001) and [epithelial cell of lung](/details-cell/CL0000082), endothelial- and epithelial-derived [CX3CL1](/details-gene/6376) likely acts as a primary gatekeeper for recruiting CX3CR1-expressing immune cells (such as monocytes and cytotoxic lymphocytes) to the lungs during viral infections or acute respiratory distress syndrome (ARDS). Dysregulation of this axis may contribute to excessive inflammation and lung injury. 2. The significant expression of [CX3CL1](/details-gene/6376) in [cerebral cortex endothelial cell](/details-cell/CL1001602) suggests that it plays a critical role in mediating communication across the blood-brain barrier. It may be essential for the homeostatic surveillance of the CNS by microglia and for recruiting peripheral immune cells during neuroinflammatory conditions like multiple sclerosis or ischemic stroke. **Experimental Approach:** To test the first hypothesis regarding the role of [CX3CL1](/details-gene/6376) in lung inflammation, a robust experimental model could be employed. One could utilize conditional knockout mice lacking [Cx3cl1](/details-gene/6376) specifically in endothelial cells (e.g., using a Cdh5-Cre driver). These mice, along with littermate controls, could be subjected to an LPS or viral-induced model of acute lung injury. The subsequent inflammatory response could be quantified by measuring immune cell infiltration into bronchoalveolar lavage fluid and lung tissue via flow cytometry and immunohistochemistry. Furthermore, lung edema, cytokine levels (e.g., TNF-alpha, IL-6), and overall lung injury scores could be assessed to determine if the absence of endothelial [CX3CL1](/details-gene/6376) is protective. **Therapeutic Potential:** The [CX3CL1](/details-gene/6376)-CX3CR1 signaling axis is a well-recognized target for inflammatory diseases. Given its role in mediating leukocyte recruitment and adhesion, [CX3CL1](/details-gene/6376) represents a promising target for therapeutic **inhibition**. The development of monoclonal antibodies that block the binding site of [CX3CL1](/details-gene/6376) or small molecule antagonists for its receptor, CX3CR1, could be effective in treating chronic inflammatory disorders characterized by excessive infiltration of monocytes/macrophages and T cells, such as atherosclerosis, inflammatory bowel disease, and rheumatoid arthritis. Such a strategy would aim to dampen the inflammatory cascade by preventing the migration and retention of key effector cells at the site of pathology.

Genular Protein ID: 938967506

Symbol: X3CL1_HUMAN

Name: Small-inducible cytokine D1

UniProtKB Accession Codes:

P78423 O00672

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTAC 1 CPTC 1 CTD 1 ChEMBL 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 EMDB 4 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 79 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 10 PDBsum 10 PRINTS 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 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: 9177350

Title: Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation.

PubMed ID: 9177350

DOI: 10.1038/42491

PubMed ID: 9024663

Title: A new class of membrane-bound chemokine with a CX3C motif.

PubMed ID: 9024663

DOI: 10.1038/385640a0

PubMed ID: 10493829

Title: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.

PubMed ID: 10493829

DOI: 10.1006/geno.1999.5927

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: 9782118

Title: Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow.

PubMed ID: 9782118

DOI: 10.1084/jem.188.8.1413

PubMed ID: 12055230

Title: Dual functions of fractalkine/CX3C ligand 1 in trafficking of perforin+/granzyme B+ cytotoxic effector lymphocytes that are defined by CX3CR1 expression.

PubMed ID: 12055230

DOI: 10.4049/jimmunol.168.12.6173

PubMed ID: 19838169

Title: Enrichment of glycopeptides for glycan structure and attachment site identification.

PubMed ID: 19838169

DOI: 10.1038/nmeth.1392

PubMed ID: 22171320

Title: Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD.

PubMed ID: 22171320

DOI: 10.1074/mcp.m111.013649

PubMed ID: 23125415

Title: Integrins alphavbeta3 and alpha4beta1 act as coreceptors for fractalkine, and the integrin-binding defective mutant of fractalkine is an antagonist of CX3CR1.

PubMed ID: 23125415

DOI: 10.4049/jimmunol.1200889

PubMed ID: 23765988

Title: A role for the chemokine receptor CCR6 in mammalian sperm motility and chemotaxis.

PubMed ID: 23765988

DOI: 10.1002/jcp.24418

PubMed ID: 24789099

Title: The chemokine fractalkine can activate integrins without CX3CR1 through direct binding to a ligand-binding site distinct from the classical RGD-binding site.

PubMed ID: 24789099

DOI: 10.1371/journal.pone.0096372

PubMed ID: 27653778

Title: Plasmodium falciparum proteins involved in cytoadherence of infected erythrocytes to chemokine CX3CL1.

PubMed ID: 27653778

DOI: 10.1038/srep33786

PubMed ID: 9931005

Title: Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1.

PubMed ID: 9931005

DOI: 10.1021/bi9820614

PubMed ID: 10770945

Title: The crystal structure of the chemokine domain of fractalkine shows a novel quaternary arrangement.

PubMed ID: 10770945

DOI: 10.1074/jbc.m002584200

PubMed ID: 21829356

Title: Structural basis of chemokine sequestration by CrmD, a poxvirus-encoded tumor necrosis factor receptor.

PubMed ID: 21829356

DOI: 10.1371/journal.ppat.1002162

PubMed ID: 25745166

Title: Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor.

PubMed ID: 25745166

DOI: 10.1126/science.aaa5026

PubMed ID: 29882741

Title: Viral GPCR US28 can signal in response to chemokine agonists of nearly unlimited structural degeneracy.

PubMed ID: 29882741

DOI: 10.7554/elife.35850

Sequence Information:

  • Length: 397
  • Mass: 42203
  • Checksum: BAC71F5080DF9CA6
  • Sequence:
    • MAPISLSWLL RLATFCHLTV LLAGQHHGVT KCNITCSKMT SKIPVALLIH YQQNQASCGK 
RAIILETRQH RLFCADPKEQ WVKDAMQHLD RQAAALTRNG GTFEKQIGEV KPRTTPAAGG 
MDESVVLEPE ATGESSSLEP TPSSQEAQRA LGTSPELPTG VTGSSGTRLP PTPKAQDGGP 
VGTELFRVPP VSTAATWQSS APHQPGPSLW AEAKTSEAPS TQDPSTQAST ASSPAPEENA 
PSEGQRVWGQ GQSPRPENSL EREEMGPVPA HTDAFQDWGP GSMAHVSVVP VSSEGTPSRE 
PVASGSWTPK AEEPIHATMD PQRLGVLITP VPDAQAATRR QAVGLLAFLG LLFCLGVAMF 
TYQSLQGCPR KMAGEMAEGL RYIPRSCGSN SYVLVPV