CX3C chemokine receptor 1 (IPR005387)

Short name: Chemokine_CX3CR1

Overlapping homologous superfamilies


Family relationships


Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role [PMID: 11544102]. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [PMID: 9689100], and endothelial cells, where they may act as either angiogenic or angiostatic factors [PMID: 7592998].

The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).

Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors [PMID: 10714678]. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [PMID: 10601351, PMID: 9500790]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).

The only CX3C chemokine identified to date is CX3C chemokine ligand 1 (CX3CL1), also known as fractalkine or neurotactin. It is a transmembrane molecule containing a chemokine domain on an extended mucin-like stalk [PMID: 9024663].

Both the adhesive and chemotactic effects of CX3CL1 are mediated through CX3C chemokine receptor type 1 (CX3CR1), also known as fractalkine receptor [PMID: 9390561]. The receptor is expressed specifically on T cells, natural killer cells and monocytes [PMID: 15786508, PMID: 7590284]. Coupling of the receptor to pertussis toxin-sensitive Gi proteins leads to calcium mobilisation and chemotaxis [PMID: 9390561]. In contrast, adhesion mediated by the receptor is insensitive to pertussis toxin and does not appear to involve calcium mobilisation. CX3CR1 has also been found to act as a weak fusion cofactor for some HIV-1 strains, an interaction that can be potently and specifically blocked by CX3CL1 [PMID: 9726990].

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway
GO:0007155 cell adhesion
GO:0006935 chemotaxis

Molecular Function

GO:0016495 C-X3-C chemokine receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.