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

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; AllianceGenome:HGNC:10647
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: mouse all
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Genomic context

Location:: 16q21

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (57372490..57385044)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (63167607..63180165)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (57406402..57418956)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Increased CX3CL1 in cerebrospinal fluid and ictal serum t-tau elevations in migraine: results from a cross-sectional exploratory case-control study.
Title: Increased CX3CL1 in cerebrospinal fluid and ictal serum t-tau elevations in migraine: results from a cross-sectional exploratory case-control study.
Direct interaction of platelet with tumor cell aggravates hepatocellular carcinoma metastasis by activating TLR4/ADAM10/CX3CL1 axis.
Title: Direct interaction of platelet with tumor cell aggravates hepatocellular carcinoma metastasis by activating TLR4/ADAM10/CX3CL1 axis.
The cytokine trio - visfatin, placental growth factor and fractalkine - and their role in myocardial infarction with non-obstructive coronary arteries (MINOCA).
Title: The cytokine trio - visfatin, placental growth factor and fractalkine - and their role in myocardial infarction with non-obstructive coronary arteries (MINOCA).
Fractalkine's dual role in inflammation and hard tissue formation in cultured human dental pulp cells.
Title: Fractalkine's dual role in inflammation and hard tissue formation in cultured human dental pulp cells.
Alpha-1 antitrypsin inhibits fractalkine-mediated monocyte-lung endothelial cell interactions.
Title: Alpha-1 antitrypsin inhibits fractalkine-mediated monocyte-lung endothelial cell interactions.
Plasma fractalkine contributes to systemic myeloid diversity and PD-L1/PD-1 blockade in lung cancer.
Title: Plasma fractalkine contributes to systemic myeloid diversity and PD-L1/PD-1 blockade in lung cancer.
CX3CL1 induces cell migration and invasion through ICAM-1 expression in oral squamous cell carcinoma cells.
Title: CX3CL1 induces cell migration and invasion through ICAM-1 expression in oral squamous cell carcinoma cells.
The Cytokine CX3CL1 and ADAMs/MMPs in Concerted Cross-Talk Influencing Neurodegenerative Diseases.
Title: The Cytokine CX3CL1 and ADAMs/MMPs in Concerted Cross-Talk Influencing Neurodegenerative Diseases.
Fractalkine Improves the Expression of Endometrium Receptivity-Related Genes and Proteins at Desferrioxamine-Induced Iron Deficiency in HEC-1A Cells.
Title: Fractalkine Improves the Expression of Endometrium Receptivity-Related Genes and Proteins at Desferrioxamine-Induced Iron Deficiency in HEC-1A Cells.
CX3CL1 promotes cell sensitivity to ferroptosis and is associated with the tumor microenvironment in clear cell renal cell carcinoma.
Title: CX3CL1 promotes cell sensitivity to ferroptosis and is associated with the tumor microenvironment in clear cell renal cell carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (299)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH86440 (e-PCR)
- UniSTS:90134

D8S2279 (e-PCR)
- UniSTS:473907

RH79608 (e-PCR)
- UniSTS:86368

D1S1423 (e-PCR)
- UniSTS:149619

D11S3114 (e-PCR)
- UniSTS:152207

RH67976 (e-PCR)
- UniSTS:57255

D16S2589E (e-PCR)
- UniSTS:51897

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables CCR chemokine receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables CX3C chemokine receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables CX3C chemokine receptor binding	NAS Non-traceable Author Statement more info	PubMed
enables CX3C chemokine receptor binding	TAS Traceable Author Statement more info	PubMed
enables CXCR1 chemokine receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables chemoattractant activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables chemokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables chemokine activity	IDA Inferred from Direct Assay more info	PubMed
enables chemokine activity	IGI Inferred from Genetic Interaction more info	PubMed
enables chemokine activity	TAS Traceable Author Statement more info	PubMed
enables integrin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in angiogenesis involved in wound healing	IEA Inferred from Electronic Annotation more info
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IBA Inferred from Biological aspect of Ancestor more info
involved_in autocrine signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell adhesion	IPI Inferred from Physical Interaction more info	PubMed
involved_in cell chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in cell-cell adhesion	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell-cell adhesion	TAS Traceable Author Statement more info	PubMed
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in chemokine-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in chemokine-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in chemokine-mediated signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cytokine-mediated signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in defense response	TAS Traceable Author Statement more info	PubMed
involved_in eosinophil chemotaxis	IBA Inferred from Biological aspect of Ancestor more info
involved_in extrinsic apoptotic signaling pathway in absence of ligand	IEA Inferred from Electronic Annotation more info
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in integrin activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in leukocyte adhesive activation	TAS Traceable Author Statement more info	PubMed
involved_in leukocyte chemotaxis	TAS Traceable Author Statement more info	PubMed
involved_in leukocyte migration involved in inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in microglial cell activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in microglial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell-substrate adhesion	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of glutamate receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of hippocampal neuron apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of interleukin-1 alpha production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interleukin-1 beta production	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of interleukin-6 production	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of neuron migration	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of tumor necrosis factor production	TAS Traceable Author Statement more info	PubMed
involved_in neuron cellular homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron remodeling	TAS Traceable Author Statement more info	PubMed
involved_in positive chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of I-kappaB phosphorylation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of MAPK cascade	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of actin filament bundle assembly	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of calcium-independent cell-cell adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell-matrix adhesion	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of inflammatory response	IEP Inferred from Expression Pattern more info	PubMed
involved_in positive regulation of microglial cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neuroblast proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of release of sequestered calcium ion into cytosol	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of smooth muscle cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transforming growth factor beta1 production	IEA Inferred from Electronic Annotation more info
involved_in regulation of lipopolysaccharide-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of neurogenesis	TAS Traceable Author Statement more info	PubMed
involved_in regulation of synaptic plasticity	TAS Traceable Author Statement more info	PubMed
involved_in response to ischemia	ISS Inferred from Sequence or Structural Similarity more info
involved_in synapse pruning	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cell projection	ISS Inferred from Sequence or Structural Similarity more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IMP Inferred from Mutant Phenotype more info	PubMed
located_in extracellular region	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in neuron projection	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed

General protein information

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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)

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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)

NM_001304392.3 → NP_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, CA396869, HY114023

UniProtKB/TrEMBL

J3QRA1

Conserved Domains (2) summary

PRK10263
Location:44 → 217

PRK10263; DNA translocase FtsK; Provisional

cl00134
Location:1 → 15

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 into 4 ...
NM_002996.6 → NP_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, HY114023

Consensus CDS

CCDS10779.1

UniProtKB/Swiss-Prot

O00672, P78423

UniProtKB/TrEMBL

A0N0N7, Q53H89, Q6I9S9

Related

ENSP00000006053.6, ENST00000006053.7

Conserved Domains (3) summary

PRK12323
Location:169 → 342

PRK12323; DNA polymerase III subunit gamma/tau

cd00274
Location:25 → 100

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 cleaved to a ...

NF033804
Location:102 → 243

Streccoc_I_II; antigen I/II family LPXTG-anchored adhesin