The CXCR1 gene (il8ra) is 4149 bp long and is composed of two exons, one of them included in the coding region (1053 bp) CXCR1 has 165 known SNPs; many of them correlate with disease states.
Genetic locus: CXCR1, together with its homolog CXCR2 (76% amino acids identity) and its pseudogene (il8rp), reside in chromosome 2q34-35. The high homology and close chromosomal localization between the three genes suggest gene duplications.

Transcripts: primer extension analysis revealed two start sites for CXCR1 (Sprenger et al., 1995). In addition, neutrophils contain two transcripts of CXCR1 (2.0 and 4.0 kb) which result from the usage of alternative poly adenylation signals.
Transcription regulators: PU.1, which belongs to the ets family of transcription factors, is a major activator of CXCR1 expression (Wilkinson and Navarro, 1999). HIF1 and NF-kappaB mediate the transcription of CXCR1 under hypoxia in prostate cancer cells (Maxwell et al., 2007). CXCR1 mRNA expression is also regulated by G-CSF (Lloyd et al., 1995).

Conservation during evolution: the CXCR1 gene was present in the common ancestor of chordates and has orthologs in diverse species, from lizards and Xenopus to primates. There is a high level of homology between CXCR1 from human, rabbit, rat, and mouse. The sequencing of the coding region of CXCR1 in worldwide human populations and 5 representative nonhuman primate species revealed accelerated protein evolution in the human lineage, mainly at the N-terminal ligand/receptor recognition domain (Liu et al., 2005).

350 amino acids, 39791 Da.
CXCR1 is a G protein coupled receptor (GPCR), composed of seven transmembrane (TM) helices, an N-terminal ligand binding domain and a signaling cytoplasmic tail.

Expression in tissues: according to SAGE (serial analysis of gene expression), CXCR1 is mainly expressed in the bone marrow, retina, heart, lungs and in the placenta.
Expression in cell types: CXCR1 is expressed on a wide variety of cell types, including neutrophils, monocytes, CD8 T cells, mast cells, basophils, natural killer cells, keratinocytes, fibroblasts, neurons, endothelial cells, and melanocytes.
Expression regulators: CXCR1 was found to be up-regulated by IL6, by a yet-unknown mechanism (Eikawa et al., 2010).

CXCR1 resides in the plasma membrane and transduces signals into the cell (figure 1).

Upon binding to its ligands, CXCR1 transduces signals via the phosphatidylinositol-calcium second messenger system and plays an important role in acute inflammation. IL-8 (CXCL8), the main ligand of CXCR1, is a powerful neutrophil chemotactic factor and its binding to CXCR1 induces activation and migration of neutrophils (Holmes et al., 1991; Liu et al., 2005). In neutrophils, receptor activation also stimulates the release of granule enzymes and the generation of superoxide in respiratory burst (Jones et al., 1996). In addition to its effect on immune cells, CXCR1 may be important in regulating vasculogenesis and consequent tumor growth (Strieter et al., 1995). The signaling pathway of CXCR1 as a G protein coupled receptor is presented in figure 1. Noteworthy, CXCR1 signaling also activates monomeric, low molecular weight G proteins of the Ras and Rho families (Laudanna et al., 1996).
Ligand selectivity: CXCR1 displays a relatively narrow selectivity and high preference for IL-8. At low affinity it also binds MGSA/GRO.