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FLASH GENE
Symbol CX3CL1 contributors: mct/npt/pgu - updated : 04-05-2011
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
    DNA
    TYPE functioning gene
    STRUCTURE 12.54 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Physical map
    LOC390733 16 similar to MTM MT1B 16q13 metallothionein 1B (functional) MT1F 16q13 metallothionein 1F (functional) MT1G 16q13 metallothionein 1G MT1H 16q13 metallothionein 1H MT1X 16q13 metallothionein 1X KIAA0095 16q13 metallothionein 1X SLC12A3 16q13 solute carrier family 12 (sodium/chloride transporters), member 3 HERPUD1 16q12.2-13 homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1 CETP 16q13 cholesteryl ester transfer protein, plasma NOD27 16q13 nucleotide-binding oligomerization domains 27 CPNE2 16q13 copine II NIP30 16q13 NEFA-interacting nuclear protein NIP30 KIAA1972 16q13 KIAA1972 protein TM4SF11 16q12-q13 transmembrane 4 superfamily member 11 (plasmolipin) BART1 CX3CL1 16q13 chemokine (C-X3-C motif) ligand 1 CCL22 16q13 chemokine (C-C motif) ligand 22 CCL17 16q13 chemokine (C-C motif) ligand 17 LOC57019 16q13-q21 hypothetical protein LOC57019 POLR2C 16q13-q21 polymerase (RNA) II (DNA directed) polypeptide C, 33kDa DOK4 16q13 docking protein 4 MGC10992 16q13 hypothetical protein LOC92922 GPR114 16q13 G protein-coupled receptor 114 LOC255519 16q13 similar to high mobility group protein homolog HMG4 GPR56 16q13 G protein-coupled receptor 56 GPR97 16q13 G protein-coupled receptor 97 DKFZp434I099 16q13 hypothetical protein DKFZp434I099 KATNB1 16q13 katanin p80 (WD repeat containing) subunit B 1 KIFC3 16q13-q21 kinesin family member C3 LOC388282 16 hypothetical gene supported by AF452719; BC041062 CNGB1 16q13 cyclic nucleotide gated channel beta 1
    RNA
    TRANSCRIPTS type messenger
    text two alternatively spliced isoforms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 3304 - 397 - 1997 9177350
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine     Homo sapiens
    Nervousbrain   highly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Digestiveepithelial cell Homo sapiens
    Lymphoid/Immunedendritic cell Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    Lymphoid/ImmuneT cell
    Skeletonosteoblast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text
  • developing kidney
  • abundant in endometrial vasculature, epithelial, and decidual cells
    • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    		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
    • HOMOLOGY
    Homologene
    FAMILY
  • small inducible cytokine subfamily D (Cys-X3-Cys)
  • intercrine delta family
    • CATEGORY adhesion , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        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
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
  • CX3CL1-CX3CR1 axis is a highly adhesive pair involved in the firm adhesion of monocytes or lymphocytes on activated endothelium
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
    • cell & other
    REGULATION
    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 )
    ASSOCIATED DISORDERS
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    allergyasthm 
    CX3CR1 and CX3CL1 may represent attractive therapeutic targets in asthma
    cancermetastases 
    CX3CL1-CX3CR1 axis may be a novel target for the therapeutic intervention of bone resorbing diseases such as cancer bone metastasis
    osteoarticularboneostéoporosis
    CX3CL1-CX3CR1 axis may be a novel target for the therapeutic intervention of bone resorbing diseases such as rheumatoid arthritis, osteoporosis
    ANIMAL & CELL MODELS