CXCR4 Gene

CXCR4 (C-X-C Motif Chemokine Receptor 4) is a protein-coding gene located on chromosome 2q22.1. Alternative transcriptional splice variants encoding different isoforms have been characterized.

The CXCR4 gene encodes a CXC chemokine receptor specific for stromal cell factor-1. The CXC chemokine receptor (like other chemokine receptors) has 7 transmembrane domains and is located on the cell surface. The receptor interacts with the CD4 protein. The HIV virus uses this receptor protein to enter the cell. CXCR4 is also highly expressed in breast cancer cells.

Mutations in the CXCR4 gene are associated with WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis). Waldenstroem macroglobulinemia is also associated with mutations in this gene.

The encoded CXCR4- protein is a receptor for the C-X-C chemokine CXCL12/SDF-1, and its associated activation induces signaling by increasing intracellular calcium ion levels resulting in enhancement of MAPK1/MAPK3 activation. Plays a role in regulating cell migration, e.g., in wound healing.

CXCR4 acts as a receptor for extracellular ubiquitin; leads to increased intracellular calcium ions and reduced cellular cAMP levels. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Is involved in hematopoiesis and in the formation of the ventricular septum. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in the development of the cerebellum.

Chemokine receptors are 7-transmembrane G protein-coupled receptors that are activated by the binding of one or more chemokines. Chemokines are a family of chemoattractant molecules, of which more than 50 have been identified to date. They are classified into four main groups according to the number and spacing of conserved cysteines: CXC, CC, CX3C and C.

1. Bachelerie F (2010) CXCL12/CXCR4-axis dysfunctions: markers of the rare immunodeficiency disorder WHIM syndrome. Dis Markers 29:189-198.
2. Pozzobon T et al (2016) CXCR4 signaling in health and disease. Immunol Lett 177:6-15.