Domain

CXC chemokine receptor 4 N-terminal domain (IPR022726)

Short name: Chemokine_CXCR4_N_dom

Domain relationships

None.

Description

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 CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.

This entry represents the N-terminal region of the CXC type 4 chemokine receptor. CXCR4 and its ligand stromal cell-derived factor-1 (also known as CXCL12) are essential for proper fetal development. CXCR4 is also the major coreceptor for T-tropic strains of Human immunodeficiency virus 1, and SDF-1 inhibits HIV-1 infection. Additionally, SDF-1 and CXCR4 mediate cancer cell migration and metastasis. The N-terminal domain of most chemokine receptors is the ligand binding domain and so the N-terminal domain of CXCR4 is the binding site for SDF-1 [PMID: 18799424].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0019955 cytokine binding

Cellular Component

No terms assigned in this category.

Contributing signatures

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