Browse CX3CL1

Summary
SymbolCX3CL1
Namechemokine (C-X3-C motif) ligand 1
Aliases C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location16q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane Single-pass type I membrane protein ; SUBCELLULAR LOCATION: Processed fractalkine: Secreted
Domain PF00048 Small cytokines (intecrine/chemokine)
Function

Acts as a ligand for both CX3CR1 and integrins. Binds to CX3CR1 (PubMed:23125415, PubMed:9931005, PubMed:21829356). Binds to integrins ITGAV:ITGB3 and ITGA4:ITGB1. Can activate integrins in both a CX3CR1-dependent and CX3CR1-independent manner. In the presence of CX3CR1, activates integrins by binding to the classical ligand-binding site (site 1) in integrins. In the absence of CX3CR1, binds to a second site (site 2) in integrins which is distinct from site 1 and enhances the binding of other integrin ligands to site 1 (PubMed:23125415, PubMed:24789099). The soluble form is chemotactic for T-cells and monocytes and not for neutrophils. The membrane-bound form promotes adhesion of those leukocytes to endothelial cells. May play a role in regulating leukocyte adhesion and migration processes at the endothelium (PubMed:9024663, PubMed:9177350).

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0001819 positive regulation of cytokine production
GO:0002523 leukocyte migration involved in inflammatory response
GO:0002548 monocyte chemotaxis
GO:0016338 calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules
GO:0030336 negative regulation of cell migration
GO:0030593 neutrophil chemotaxis
GO:0030595 leukocyte chemotaxis
GO:0031349 positive regulation of defense response
GO:0032103 positive regulation of response to external stimulus
GO:0032905 transforming growth factor beta1 production
GO:0032908 regulation of transforming growth factor beta1 production
GO:0032914 positive regulation of transforming growth factor beta1 production
GO:0033622 integrin activation
GO:0034341 response to interferon-gamma
GO:0034612 response to tumor necrosis factor
GO:0038034 signal transduction in absence of ligand
GO:0040013 negative regulation of locomotion
GO:0043410 positive regulation of MAPK cascade
GO:0045123 cellular extravasation
GO:0045765 regulation of angiogenesis
GO:0045766 positive regulation of angiogenesis
GO:0045785 positive regulation of cell adhesion
GO:0048246 macrophage chemotaxis
GO:0048247 lymphocyte chemotaxis
GO:0048514 blood vessel morphogenesis
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050900 leukocyte migration
GO:0050902 leukocyte adhesive activation
GO:0051040 regulation of calcium-independent cell-cell adhesion
GO:0051041 positive regulation of calcium-independent cell-cell adhesion
GO:0051271 negative regulation of cellular component movement
GO:0060055 angiogenesis involved in wound healing
GO:0060326 cell chemotaxis
GO:0070098 chemokine-mediated signaling pathway
GO:0070371 ERK1 and ERK2 cascade
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070555 response to interleukin-1
GO:0071346 cellular response to interferon-gamma
GO:0071347 cellular response to interleukin-1
GO:0071356 cellular response to tumor necrosis factor
GO:0071604 transforming growth factor beta production
GO:0071621 granulocyte chemotaxis
GO:0071634 regulation of transforming growth factor beta production
GO:0071636 positive regulation of transforming growth factor beta production
GO:0071674 mononuclear cell migration
GO:0072676 lymphocyte migration
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0097529 myeloid leukocyte migration
GO:0097530 granulocyte migration
GO:0098742 cell-cell adhesion via plasma-membrane adhesion molecules
GO:1901099 negative regulation of signal transduction in absence of ligand
GO:1901342 regulation of vasculature development
GO:1904018 positive regulation of vasculature development
GO:1990266 neutrophil migration
GO:2000146 negative regulation of cell motility
GO:2001233 regulation of apoptotic signaling pathway
GO:2001234 negative regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
GO:2001239 regulation of extrinsic apoptotic signaling pathway in absence of ligand
GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
Molecular Function GO:0001664 G-protein coupled receptor binding
GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
GO:0005178 integrin binding
GO:0008009 chemokine activity
GO:0031737 CX3C chemokine receptor binding
GO:0042379 chemokine receptor binding
GO:0048020 CCR chemokine receptor binding
GO:0050839 cell adhesion molecule binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04062 Chemokine signaling pathway
hsa04668 TNF signaling pathway
Reactome R-HSA-380108: Chemokine receptors bind chemokines
R-HSA-373076: Class A/1 (Rhodopsin-like receptors)
R-HSA-500792: GPCR ligand binding
R-HSA-375276: Peptide ligand-binding receptors
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
Summary
SymbolCX3CL1
Namechemokine (C-X3-C motif) ligand 1
Aliases C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location16q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CX3CL1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between CX3CL1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25428504MelanomaInhibit immunity (T cell function); resistant to immunotherapyFurthermore, responses were associated with T-helper type 1 (TH1) gene expression, CTLA4 expression and the absence of fractalkine (CX3CL1) in baseline tumour specimens.
17372897B16 Malignant MelanomaPromote immunityWe found that B16-treated CX3CR1-/- mice had increased lung tumor burden and cachexia. However, CX3CR1-deficient NK cells exhibited a tumorigenic cytokine production profile with defective IFN-gamma expression and enhanced IL-6 production in response to TLR3 activation with polyIC. Our studies indicate that CX3CR1 is an important contributor to innate immunity at multiple levels.
17332365NeuroblastomaPromote immunityTherefore, we tested the hypothesis that a combined increase of FKN and interleukin-2 (IL-2) in the neuroblastoma microenvironment induces an effective antitumor immune response. The depletion of T cells and NK cells in vivo abrogated the effect, and these effector cells showed the highest cytolytic activity in vitro. Finally, only the FKN- and IL-2-enriched neuroblastoma microenvironment resulted in T-cell activation and the release of proinflammatory cytokines.
Summary
SymbolCX3CL1
Namechemokine (C-X3-C motif) ligand 1
Aliases C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location16q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CX3CL1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCX3CL1
Namechemokine (C-X3-C motif) ligand 1
Aliases C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location16q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CX3CL1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.7440.153
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.7130.702
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.7730.564
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.3650.549
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.6710.695
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.020.993
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.1010.824
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.1040.93
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1590.907
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.8390.668
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.8440.765
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2480.194
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CX3CL1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86016.7-16.70.429
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCX3CL1
Namechemokine (C-X3-C motif) ligand 1
Aliases C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location16q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CX3CL1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCX3CL1
Namechemokine (C-X3-C motif) ligand 1
Aliases C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location16q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CX3CL1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CX3CL1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCX3CL1
Namechemokine (C-X3-C motif) ligand 1
Aliases C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location16q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CX3CL1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCX3CL1
Namechemokine (C-X3-C motif) ligand 1
Aliases C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location16q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CX3CL1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCX3CL1
Namechemokine (C-X3-C motif) ligand 1
Aliases C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location16q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CX3CL1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCX3CL1
Namechemokine (C-X3-C motif) ligand 1
Aliases C3Xkine; ABCD-3; CXC3C; CXC3; fractalkine; neurotactin; SCYD1; small inducible cytokine subfamily D (Cys-X3- ......
Chromosomal Location16q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CX3CL1 collected from DrugBank database.
> Drugs from DrugBank database
 

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