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Symbol CX3CL1 contributors: mct/npt/pgu - updated : 28-09-2020
HGNC name chemokine (C-X3-C motif) ligand 1
HGNC id 10647
Location 16q13      Physical location : 57.406.413 - 57.418.954
Synonym name
  • neurotactin
  • small inducible cytokine subfamily D (Cys-X3-Cys), member 1 (fractalkine, neurotactin)
  • fractalkine
  • neurotactin
  • Synonym symbol(s) NRTC, CXC3C, SCYD1, NTN, CXC3, ABCD3, C3Xkine, FKN, NTT, SCYD1
    TYPE functioning gene
    STRUCTURE 12.56 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    TRANSCRIPTS type messenger
    text two alternatively spliced isoforms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 3285 - 397 - 1997 9177350
    2 - 3164 - 312 - 1997 9177350
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine     Homo sapiens
    Endocrinepancreas     Homo sapiens
    Nervousbrainforebraincerebral cortex   Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Homo sapiens
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Lymphoid/Immunedendritic cell Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    Lymphoid/ImmuneT cell
    Nervousglia Homo sapiens
    Nervousneuron Homo sapiens
    Skeletonosteoblast Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period embryo
  • developing kidney
  • abundant in endometrial vasculature, epithelial, and decidual cells
    a chemokine domain with 76 AAs :
  • N terminus up to the first cysteine (Cys-8)
  • a long loop followed by a three-stranded antiparallel beta-sheet (residues 24–51)
  • a mucin stalk domain (241 AAs)
  • a membrane associated structure (18 AAs)
  • a stretch of hydrophobic residues towards the C terminus
  • a C-terminal alpha-helix (residues 56–67) packed against the beta-sheet, and C-terminus carries important determinants for cellular trafficking but not for function of the chemokine during leukocyte recruitment
  • cytoplasmic tail facilitating its constitutive clathrin-mediated endocytosis
  • small inducible cytokine subfamily D (Cys-X3-Cys)
  • intercrine delta family, CX3C family
  • CATEGORY adhesion , signaling cytokine
        plasma membrane
    basic FUNCTION
  • involved in recruitment of T cells for interaction with mature dendritic cell in the immune response
  • chemotactic for neutrophils with direct role in cell adhesion
  • involved in mononuclear cell recruitment into atherosclerotic lesions and in inflammatory response
  • playing a major role in promoting adhesion of monocytic cells to activated smooth muscle cells
  • involved in the control of leukocyte traffic at the endothelium
  • increasing cell-cell adhesion and aortic smooth muscle proliferation, indicating a role in initiation and progression of atherosclerotic vascular disease
  • promote trophoblast migration (having direct effects with CCL14 on trophoblast adhesion molecules and ECM, suggesting mechanisms by which trophoblast cells migrate during early pregnancy)
  • role of CX3CL1 in osteoblast-induced osteoclast differentiation
  • soluble CX3CL1 induced migration of bone marrow cells containing osteoclast precursors, whereas immobilized CX3CL1 mediated firm adhesion of osteoclast precursors
  • may play a key role in the mechanism of angiogenesis and carcinogenesis of hepatocellular carcinoma (
  • expressed on both endothelial and epithelial cells induces leukocyte transmigration, via the DRY motif and C-terminus of CX3CR1 and the activity of ADAM10 (
  • CX3CR1 and CX3CL1 are required for the survival of both TH1 and TH2 cells in inflamed airways
  • CX3CL1 exerts cytotoxic effects on the endothelium as well as anti-apoptotic and proliferative effects on vascular cells, affecting the context and stability of the atherosclerotic plaque
  • important pathogenic role of CX3CL1/CX3CR1 in atherogenesis and plaque destabilization
  • islets express and secrete CX3CL1 and CX3CL1 impacts them by decreasing glucagon secretion without affecting insulin secretion
  • fractalkine present at the apical microvillous plasma membrane of the syncytiotrophoblast may mediate close interaction of placental villi with circulating maternal blood cells
  • fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules
  • CX3CL1 has a major role in the progression of Alzheimer Disease
  • CX3CL1 and its receptor CX3CR1 play a fundamental role in the pathophysiology of stroke
  • CX3CL1/CX3CR1 communication system has anti-inflammatory and neuroprotective effects and plays an important role in maintaining autophagy activity
  • CX3CL1 is essential in the crosstalk between neurons and microglia
  • chemokine involved in the anticancer function of lymphocytes-mainly NK cells, T cells and dendritic cells 0
    PHYSIOLOGICAL PROCESS immunity/defense
    a component
  • CX3CL1-CX3CR1 axis is a highly adhesive pair involved in the firm adhesion of monocytes or lymphocytes on activated endothelium
    small molecule
  • CX3CR1 (to function as a chemoattractant and adhesion protein)
  • cleaved by ADAM10
  • CX3CL1-CX3CR1 axis is central in defenses against neurodegenerative disorders and against several cancers, and also involved in various inflammatory diseases, including renal inflammation and atherosclerosis
  • CCL26 is yet a functional ligand for CX3CR1, the receptor for fractalkine/CX3CL1, which is expressed by CD16(+) NK cells, cytotoxic effector CD8(+) T cells, and CD14(low)CD16(high) monocytes
  • CX3CL1 protects beta-cells from the adverse effects of TNF on their function by restoring the expression and phosphorylation of key proteins of the insulin secretion pathway
  • CX3CL1/CX3CR1 axis acts in many physiological phenomena including those occurring in the central nervous system (CNS), by regulating the interactions between neurons, microglia, and immune cells
  • CX3CL1 is secreted by neurons and plays an important role in modulating glial activation in the central nervous system after binding to its sole receptor CX3CR1 which mainly is expressed on microglia
  • CX3CL1/CX3CR1 contributes positively to neuron protective as well as detrimental role in the course of the disease
  • CX3CR1/CX3CL1 axis plays a key role in the phagocytosis of MAPT by microglia and that it is affected as Alzheimer disease progresses
  • CX3CL1 activates the pro-inflammatory pathway mediated by the transcription factor NFKB1 as an early response in microglial cells
  • role of MSK1 in the induction of NFKB1 by the chemokine CX3CL1 in microglial cells
  • cell & other
    activated by upregulated upon dendritic cell maturation
    RETN (resistin up-regulated its expression at comparable level to that of TNF by a mechanism involving MAPK14 and JNK MAPK and NF-kappaB)
    induced by IFNG and TNFA during vascular inflammation
    Other regulated by ADAM17 (cleavage and shedding )
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in airway smooth muscle, lung endothelium and epithelium upon allergen challenge, in people with asthma
    constitutional     --over  
    increased in patients with chronic heart failure, in accordance with disease severity
    Variant & Polymorphism
    Candidate gene
    Therapy target
    CX3CR1 and CX3CL1 may represent attractive therapeutic targets in asthma
    CX3CL1-CX3CR1 axis may be a novel target for the therapeutic intervention of bone resorbing diseases such as cancer bone metastasis
    CX3CL1-CX3CR1 axis may be a novel target for the therapeutic intervention of bone resorbing diseases such as rheumatoid arthritis, osteoporosis
    CX3CL1/CX3CR1 communication system is a therapeutic target for amyotrophic lateral sclerosis (ALS)patients
    CX3CL1-CX3CR1 signaling is a molecular mechanism capable of modulating microglial-mediated degeneration and represents a potential molecular target in therapeutic approaches to RP