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CX3CL1 C-X3-C motif chemokine ligand 1 [ Homo sapiens (human) ]

Gene ID: 6376, updated on 12-Aug-2018

Summary

Official Symbol
CX3CL1provided by HGNC
Official Full Name
C-X3-C motif chemokine ligand 1provided by HGNC
Primary source
HGNC:HGNC:10647
See related
Ensembl:ENSG00000006210 MIM:601880; Vega:OTTHUMG00000133469
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
NTN; NTT; CXC3; CXC3C; SCYD1; ABCD-3; C3Xkine; fractalkine; neurotactin
Summary
This gene belongs to the CX3C subgroup of chemokines, characterized by the number of amino acids located between the conserved cysteine residues. This is the only member of the CX3C subgroup, which contains three amino acids between cysteine residues, resulting in a Cys-X-X-X-Cys configuration. The encoded protein contains an extended mucin-like stalk with a chemokine domain on top, and exists in both a membrane-anchored form where it acts as a binding molecule, or, in soluble form, as a chemotactic cytokine. The mature form of this protein can be cleaved at the cell surface, yielding different soluble forms that can interact with the G-protein coupled receptor, C-X3-C motif chemokine receptor 1 gene product. This gene plays a role in a wide range of diseases, including cancer, vasculitis, neuropathies, atherosclerosis, inflammatory diseases, and in human immunodeficiency virus infections. [provided by RefSeq, Sep 2017]
Expression
Broad expression in brain (RPKM 40.1), lung (RPKM 37.8) and 21 other tissues See more
Orthologs

Genomic context

See CX3CL1 in Genome Data Viewer
Location:
16q21
Exon count:
3
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 16 NC_000016.10 (57372458..57385048)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (57406414..57418956)

Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene ribosomal protein L23a pseudogene 91 Neighboring gene C-C motif chemokine ligand 22 Neighboring gene C-C motif chemokine ligand 17 Neighboring gene cytokine induced apoptosis inhibitor 1 Neighboring gene coenzyme Q9

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Upregulation of the human proteins CCL2, CX3CL1, IL-1beta, and CXCL10 by HIV-1 gp120 involves CB2 receptor in mesencephalic neuronal/glial culture model PubMed
env Chemokines such as fractalkine, macrophage-derived chemokine (MDC), RANTES, and SDF-1alpha are able to block gp120-induced apoptosis of hippocampal neurons; both fractalkine and MDC activate ERK-1/2, while SDF-1alpha activates CREB PubMed
env Fractalkine (CX3CL1) protects hippocampal neurons from the neurotoxicity induced by the HIV-1 envelope protein gp120, and neuronal CX(3)CR1 receptors and Akt activation are responsible for the neuroprotective effects of fractalkine PubMed
Tat tat HIV-1 Tat-mediated downregulation of CX3CR1 inhibits CX3CL1-induced migration of microglia PubMed
tat Pretreatment of microglia with HIV-1 Tat followed by treatment with CX3CL1 results in inhibition of CX3CL1-mediated activation of ERK1/2 and JNK MAPKs compared to cells not treated with Tat PubMed
tat Fractalkine-CX3CR1 signaling contributes to the inhibition of the synergistic neurotoxic effects by opioids and HIV-1 Tat PubMed
tat Fractalkine is neuroprotective to cultured neurons when co-administered with HIV-1 Tat, a viral protein that induces neuronal apoptosis PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Chemokine receptors bind chemokines, organism-specific biosystem (from REACTOME)
    Chemokine receptors bind chemokines, organism-specific biosystemChemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. Following interaction, these receptors trigger a flux of i...
  • Chemokine signaling pathway, organism-specific biosystem (from KEGG)
    Chemokine signaling pathway, organism-specific biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
  • Chemokine signaling pathway, conserved biosystem (from KEGG)
    Chemokine signaling pathway, conserved biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
  • Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
    Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
  • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Direct p53 effectors, organism-specific biosystem (from Pathway Interaction Database)
    Direct p53 effectors, organism-specific biosystem
    Direct p53 effectors
  • GPCR ligand binding, organism-specific biosystem (from REACTOME)
    GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
  • Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
    Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by GPCR, organism-specific biosystem (from REACTOME)
    Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
  • TNF signaling pathway, organism-specific biosystem (from KEGG)
    TNF signaling pathway, organism-specific biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
  • TNF signaling pathway, conserved biosystem (from KEGG)
    TNF signaling pathway, conserved biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
CCR chemokine receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
CX3C chemokine receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
CX3C chemokine receptor binding NAS
Non-traceable Author Statement
more info
PubMed 
CX3C chemokine receptor binding TAS
Traceable Author Statement
more info
PubMed 
CXCR1 chemokine receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
chemoattractant activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
chemokine activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemokine activity IDA
Inferred from Direct Assay
more info
PubMed 
chemokine activity IGI
Inferred from Genetic Interaction
more info
PubMed 
chemokine activity TAS
Traceable Author Statement
more info
PubMed 
integrin binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor binding TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
G-protein coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
G-protein coupled receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
G-protein coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 
aging ISS
Inferred from Sequence or Structural Similarity
more info
 
angiogenesis involved in wound healing IEA
Inferred from Electronic Annotation
more info
 
autocrine signaling ISS
Inferred from Sequence or Structural Similarity
more info
 
cell adhesion IPI
Inferred from Physical Interaction
more info
PubMed 
cell-cell adhesion ISS
Inferred from Sequence or Structural Similarity
more info
 
cell-cell adhesion TAS
Traceable Author Statement
more info
PubMed 
cell-cell signaling TAS
Traceable Author Statement
more info
PubMed 
cellular response to interferon-gamma IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to interleukin-1 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to tumor necrosis factor IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemokine-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
chemotaxis IMP
Inferred from Mutant Phenotype
more info
PubMed 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
PubMed 
defense response TAS
Traceable Author Statement
more info
PubMed 
eosinophil chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
immune response TAS
Traceable Author Statement
more info
PubMed 
inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
integrin activation IMP
Inferred from Mutant Phenotype
more info
PubMed 
leukocyte adhesive activation TAS
Traceable Author Statement
more info
PubMed 
leukocyte chemotaxis TAS
Traceable Author Statement
more info
PubMed 
leukocyte migration involved in inflammatory response IMP
Inferred from Mutant Phenotype
more info
PubMed 
lymphocyte chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
macrophage chemotaxis IEA
Inferred from Electronic Annotation
more info
 
microglial cell activation ISS
Inferred from Sequence or Structural Similarity
more info
 
microglial cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
monocyte chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of apoptotic signaling pathway IGI
Inferred from Genetic Interaction
more info
PubMed 
negative regulation of cell migration IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell-substrate adhesion NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand IEA
Inferred from Electronic Annotation
more info
 
negative regulation of glutamate receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of hippocampal neuron apoptotic process IGI
Inferred from Genetic Interaction
more info
PubMed 
negative regulation of interleukin-1 alpha production ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of interleukin-1 beta production TAS
Traceable Author Statement
more info
PubMed 
negative regulation of interleukin-6 production TAS
Traceable Author Statement
more info
PubMed 
negative regulation of microglial cell activation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of neuron migration TAS
Traceable Author Statement
more info
PubMed 
negative regulation of tumor necrosis factor production TAS
Traceable Author Statement
more info
PubMed 
negative regulation of tumor necrosis factor secretion IDA
Inferred from Direct Assay
more info
PubMed 
neuron cellular homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
neuron remodeling TAS
Traceable Author Statement
more info
PubMed 
neutrophil chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive chemotaxis IEA
Inferred from Electronic Annotation
more info
 
positive regulation of ERK1 and ERK2 cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of ERK1 and ERK2 cascade TAS
Traceable Author Statement
more info
PubMed 
positive regulation of GTPase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of I-kappaB kinase/NF-kappaB signaling ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of I-kappaB phosphorylation IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of MAPK cascade IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of actin filament bundle assembly IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of angiogenesis IEA
Inferred from Electronic Annotation
more info
 
positive regulation of calcium-independent cell-cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell-matrix adhesion TAS
Traceable Author Statement
more info
PubMed 
positive regulation of inflammatory response IEP
Inferred from Expression Pattern
more info
PubMed 
positive regulation of neuroblast proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of neuron projection development ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of protein kinase B signaling IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of protein kinase B signaling ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of release of sequestered calcium ion into cytosol IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of smooth muscle cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transforming growth factor beta1 production IEA
Inferred from Electronic Annotation
more info
 
regulation of lipopolysaccharide-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
regulation of neurogenesis TAS
Traceable Author Statement
more info
PubMed 
regulation of signaling receptor activity IEA
Inferred from Electronic Annotation
more info
 
regulation of synaptic plasticity TAS
Traceable Author Statement
more info
PubMed 
response to ischemia ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
cell projection ISS
Inferred from Sequence or Structural Similarity
more info
 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
extracellular region IDA
Inferred from Direct Assay
more info
PubMed 
extracellular region IMP
Inferred from Mutant Phenotype
more info
PubMed 
extracellular region ISS
Inferred from Sequence or Structural Similarity
more info
 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
integral component of membrane IDA
Inferred from Direct Assay
more info
PubMed 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
neuron projection IEA
Inferred from Electronic Annotation
more info
 
neuronal cell body ISS
Inferred from Sequence or Structural Similarity
more info
 
perinuclear region of cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 
plasma membrane TAS
Traceable Author Statement
more info
PubMed 

General protein information

Preferred Names
fractalkine
Names
C-X3-C motif chemokine 1
CX3C membrane-anchored chemokine
chemokine (C-X3-C motif) ligand 1
small inducible cytokine subfamily D (Cys-X3-Cys), member 1 (fractalkine, neurotactin)
small inducible cytokine subfamily D (Cys-X3-Cys), member-1
small-inducible cytokine D1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001304392.2NP_001291321.1  fractalkine isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate exon in the 5' end and initiates translation at an alternate start codon compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AC009052, BC001163, BP251342, CA396869, GU047346, HY114023
    Conserved Domains (1) summary
    cl00134
    Location:115
    Chemokine; Chemokine: small cytokines, including a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; distinguished from other cytokines by their receptors, which are G-protein coupled receptors; divided ...
  2. NM_002996.5NP_002987.1  fractalkine isoform 1 precursor

    See identical proteins and their annotated locations for NP_002987.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC009052, BC001163, BP251342, GU047346, HY114023
    Consensus CDS
    CCDS10779.1
    UniProtKB/Swiss-Prot
    P78423
    UniProtKB/TrEMBL
    A0N0N7
    Related
    ENSP00000006053.6, OTTHUMP00000164674, ENST00000006053.6
    Conserved Domains (2) summary
    cd00274
    Location:25100
    Chemokine_CX3C; Chemokine_CX3C: 1 of 4 subgroup designations based on the arrangement of the two N-terminal cysteines; differ structurally from the other subgroups in that they are attached to a membrane-spanning domain via a mucin-like stalk and can be proteolytically ...
    cl28271
    Location:131324
    dnaA; chromosomal replication initiation protein; Provisional

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000016.10 Reference GRCh38.p12 Primary Assembly

    Range
    57372458..57385048
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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