Alternative titles; symbols
HGNC Approved Gene Symbol: CXCL6
Cytogenetic location: 4q13.3 Genomic coordinates (GRCh38): 4:73,836,678-73,838,760 (from NCBI)
Chemokines are a group of small (approximately 8-14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC, based on the arrangement of the first 2 of the 4 conserved cysteine residues; the 2 cysteines are separated by a single amino acid in CXC chemokines and are adjacent in CC chemokines. CXC chemokines are further subdivided into ELR and non-ELR types based on the presence or absence of a glu-leu-arg sequence adjacent and N terminal to the CXC motif (summary by Strieter et al., 1995; Zlotnik and Yoshie, 2000).
The best characterized granulocyte chemotactic protein is interleukin-8 (IL8; 146930), also known as GCP1. Proost et al. (1993) isolated a new human granulocyte chemotactic protein, GCP2, coproduced with IL8 by osteosarcoma cells. They found that human and bovine GCP2 are 67% identical at the amino acid level. Their sequences showed only weak similarity with that of IL8, and human GCP2 did not crossreact in a radioimmunoassay for IL8.
Rovai et al. (1997) cloned the human GCP2 gene, as well as epithelial cell-derived neutrophil-activating peptide-78 (ENA78, or SCYB5; 600324). Both coding and noncoding portions of the GCP2 gene share very high nucleotide similarity to ENA78, except for the occurrence of a long interspersed sequence 5-prime of the GCP2 gene. The GCP2 gene encodes a propeptide of 114 amino acids. Despite 85% identity of the first 270 nucleotides 5-prime of the transcription start sites, GCP2 and the other CXC chemokine gene ENA78 showed cell-specific differences in regulation.
Wuyts et al. (1997) synthesized and purified a human GCP2 protein of 75 amino acids. In vitro, synthetic GCP2 was an equally active chemoattractant for neutrophilic granulocytes as was natural 75-amino acid GCP2. Synthetic GCP2 did not stimulate eosinophil, monocyte, or lymphocyte chemotaxis.
Wuyts et al. (1997) showed that GCP2 binds to the chemokine receptors CXCR1 and CXCR2. In vivo studies in rabbit demonstrated that GCP2 is a potent inflammatory mediator.
Using PCR of a radiation hybrid panel, Modi and Chen (1998) mapped the GCP2 gene to an 1.8-cR interval on chromosome 4q. This tight cluster contains many members of the CXC chemokine subfamily, and 2 additional genes, IL8 and MIG (601704), are located about 6 cR distal to this group. Modi and Chen (1998) suggested that these chemokine genes are all derived through tandem gene duplication from an ancestral gene located on chromosome 4, and that the position of SDF1 (600835) on chromosome 10 represents a translocation event.
By PCR analysis and mapping of YAC clones, O'Donovan et al. (1999) localized a number of CXC chemokine genes to 4q12-q21. They proposed that the order in this region is centromere--IL8--GRO1 (155730)/PPBP (121010)/PF4 (173460)--SCYB5/SCYB6--GRO2 (139110)/GRO3 (139111)--SCYB11 (604852)--SCYB10 (147310)--MIG--telomere. The SCYB6 gene was mapped to 4q12-q13.
Modi, W. S., Chen, Z.-Q. Localization of the human CXC chemokine subfamily on the long arm of chromosome 4 using radiation hybrids. Genomics 47: 136-139, 1998. [PubMed: 9465307] [Full Text: https://doi.org/10.1006/geno.1997.5100]
O'Donovan, N., Galvin, M., Morgan, J. G. Physical mapping of the CXC chemokine locus on human chromosome 4. Cytogenet. Cell Genet. 84: 39-42, 1999. [PubMed: 10343098] [Full Text: https://doi.org/10.1159/000015209]
Proost, P., Wuyts, A., Conings, R., Lenaerts, J.-P., Billiau, A., Opdenakker, G., Van Damme, J. Human and bovine granulocyte chemotactic protein-2: complete amino acid sequence and functional characterization as chemokines. Biochemistry 32: 10170-10177, 1993. [PubMed: 8399143] [Full Text: https://doi.org/10.1021/bi00089a037]
Rovai, L. E., Herschman, H. R., Smith, J. B. Cloning and characterization of the human granulocyte chemotactic protein-2 gene. J. Immun. 158: 5257-5266, 1997. [PubMed: 9164944]
Strieter, R. M., Polverini, P. J., Arenberg, D. A., Kunkel, S. L. The role of CXC chemokines as regulators of angiogenesis. Shock 4: 155-160, 1995. [PubMed: 8574748] [Full Text: https://doi.org/10.1097/00024382-199509000-00001]
Wuyts, A., van Osselaer, N., Haelens, A., Samson, I., Herdewijn, P., Ben-Baruch, A., Oppenheim, J. J., Proost, P., van Damme, J. Characterization of synthetic human granulocyte chemotactic protein 2: usage of chemokine receptors CXCR1 and CXCR2 and in vivo inflammatory properties. Biochemistry 36: 2716-2723, 1997. [PubMed: 9054580] [Full Text: https://doi.org/10.1021/bi961999z]
Zlotnik, A., Yoshie, O. Chemokines: a new classification system and their role in immunity. Immunity 12: 121-127, 2000. [PubMed: 10714678] [Full Text: https://doi.org/10.1016/s1074-7613(00)80165-x]