CX3CL1
Fractalkine
Also known as: ABCD-3, C3Xkine, CXC3, CXC3C, NTN, SCYD1, X3CL1_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P78423
- Gene
- CX3CL1
- Ensembl
- ENSG00000006210
- Chromosome
- 16
- Canonical length
- 397 aa
- Protein class
- Plasma proteins, Predicted membrane proteins, Predicted secreted proteins
- Subcellular location
- Plasma membrane
- Secretome location
- Secreted to blood
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
397 residues, UniProt reviewed canonical sequence.
>P78423|CX3CL1
1 MAPISLSWLL RLATFCHLTV LLAGQHHGVT KCNITCSKMT SKIPVALLIH YQQNQASCGK
61 RAIILETRQH RLFCADPKEQ WVKDAMQHLD RQAAALTRNG GTFEKQIGEV KPRTTPAAGG
121 MDESVVLEPE ATGESSSLEP TPSSQEAQRA LGTSPELPTG VTGSSGTRLP PTPKAQDGGP
181 VGTELFRVPP VSTAATWQSS APHQPGPSLW AEAKTSEAPS TQDPSTQAST ASSPAPEENA
241 PSEGQRVWGQ GQSPRPENSL EREEMGPVPA HTDAFQDWGP GSMAHVSVVP VSSEGTPSRE
301 PVASGSWTPK AEEPIHATMD PQRLGVLITP VPDAQAATRR QAVGLLAFLG LLFCLGVAMF
361 TYQSLQGCPR KMAGEMAEGL RYIPRSCGSN SYVLVPVLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CX3CL1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.61
- Highest tissue expression
- 101 nTPM
Expression across tissuesHPA
Tissue
- breast: 101 nTPM
- lung: 94 nTPM
- salivary gland: 70 nTPM
- blood vessel: 69 nTPM
- adipose tissue: 65 nTPM
- cerebral cortex: 58 nTPM
Single-cell type
- breast secretory cells: 133 nCPM
- vascular endothelial cells: 93 nCPM
- pancreatic duct cells: 78 nCPM
- salivary duct cells: 71 nCPM
- epididymal clear cells: 69 nCPM
- submucosal glandular cells: 65 nCPM
Immune cell
- basophil: 0.2 nTPM
- neutrophil: 0.1 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
Brain region
- hippocampal formation: 96 nTPM
- cerebral cortex: 91 nTPM
- basal ganglia: 77 nTPM
- amygdala: 68 nTPM
- thalamus: 63 nTPM
- white matter: 62 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CX3CL1.
Disease | ImmuneIEDB
Conditions an epitope on CX3CL1 was assayed in.
- type 1 diabetes mellitus T cell
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.55
- gnomAD pLI
- 0.61
- gnomAD missense Z
- 0.84
- DepMap mean gene effect
- -0.01
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- angiogenesis involved in wound healing
- antimicrobial humoral immune response mediated by antimicrobial peptide
- autocrine signaling
- cell adhesion
- cell chemotaxis
- cell-cell adhesion
- cell-cell signaling
- chemokine-mediated signaling pathway
- chemotaxis
- cytokine-mediated signaling pathway
- defense response
- eosinophil chemotaxis
- extrinsic apoptotic signaling pathway in absence of ligand
- G protein-coupled receptor signaling pathway
- immune response
- inflammatory response
- integrin activation
- leukocyte adhesive activation
- leukocyte chemotaxis
- leukocyte migration involved in inflammatory response
- lymphocyte chemotaxis
- macrophage chemotaxis
- microglial cell activation
- microglial cell proliferation
- negative regulation of apoptotic process
- negative regulation of apoptotic signaling pathway
- negative regulation of cell migration
- negative regulation of cell-substrate adhesion
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- negative regulation of glutamate receptor signaling pathway
- negative regulation of hippocampal neuron apoptotic process
- negative regulation of interleukin-1 alpha production
- negative regulation of interleukin-1 beta production
- negative regulation of interleukin-6 production
- negative regulation of microglial cell activation
- negative regulation of neuron migration
- negative regulation of tumor necrosis factor production
- neuron cellular homeostasis
- neuron remodeling
- neutrophil chemotaxis
- positive chemotaxis
- positive regulation of actin filament bundle assembly
- positive regulation of angiogenesis
- positive regulation of canonical NF-kappaB signal transduction
- positive regulation of cell migration
- positive regulation of cell population proliferation
- positive regulation of cell-matrix adhesion
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of inflammatory response
- positive regulation of MAPK cascade
- positive regulation of microglial cell migration
- positive regulation of neuroblast proliferation
- positive regulation of neuron projection development
- positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- positive regulation of release of sequestered calcium ion into cytosol
- positive regulation of smooth muscle cell proliferation
- positive regulation of transcription by RNA polymerase II
- positive regulation of transforming growth factor beta1 production
- regulation of lipopolysaccharide-mediated signaling pathway
- regulation of neurogenesis
- regulation of synaptic plasticity
- response to ischemia
- synapse pruning
- positive regulation of calcium-independent cell-cell adhesion
Molecular functions
- CCR chemokine receptor binding
- chemoattractant activity
- chemokine activity
- CX3C chemokine receptor binding
- integrin binding
- signaling receptor binding
- CXCR1 chemokine receptor binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CX3CL1 as an antibody target. Whether an autoantibody or antibody against CX3CL1 could matter depends on whether native CX3CL1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CX3CL1 is annotated at the cell surface, where native CX3CL1 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label CX3CL1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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