Alternative titles; symbols
HGNC Approved Gene Symbol: CXCL3
Cytogenetic location: 4q13.3 Genomic coordinates (GRCh38) : 4:74,036,589-74,038,689 (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 GRO gene (GRO1; 155730) was initially identified by Anisowicz et al. (1987) by its constitutive overexpression in spontaneously transformed Chinese hamster fibroblasts. (The name GRO stood for growth-related.) Subsequently, a protein with melanoma growth-stimulating activity (MGSA) was shown to be identical. Haskill et al. (1990) reported the identification of 2 other GRO genes, which they called GRO-beta (GRO2; 139110) and GRO-gamma. These 2 share 90% and 86% identity at the deduced amino acid level with the original GRO-alpha isolate. One amino acid substitution, proline in GRO-alpha by leucine in GRO-beta and GRO-gamma, leads to a large predicted change in protein conformation. Significant differences were also found in the 3-prime untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirmed that the 3 forms are derived from related but different genes. It appeared that all 3 genes mapped to 4q21. Expression studies revealed tissue-specific regulation as well as regulation by specific inducing agents, including interleukin-1, tumor necrosis factor, and lipopolysaccharide.
Tekamp-Olson et al. (1990) used a cDNA clone of murine macrophage inflammatory protein-2 (Mip2) to clone cDNAs for 2 human homologs, MIP2-alpha and MIP2-beta, which are highly homologous to each other and to the previously isolated gene for MGSA. Thus, the 3 GRO genes represent the human homologs of the murine Mip2 gene.
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 (146930)--GRO1/PPBP (121010)/PF4 (173460)--SCYB5 (600324)/SCYB6 (138965)--GRO2/GRO3--SCYB11 (604852)--SCYB10 (147310)--MIG (601704)--telomere. The GRO3 gene was localized to 4q12-q13.
Anisowicz, A., Bardwell, L., Sager, R. Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells. Proc. Nat. Acad. Sci. 84: 7188-7192, 1987. [PubMed: 2890161] [Full Text: https://doi.org/10.1073/pnas.84.20.7188]
Haskill, S., Peace, A., Morris, J., Sporn, S. A., Anisowicz, A., Lee, S. W., Smith, T., Martin, G., Ralph, P., Sager, R. Identification of three related human GRO genes encoding cytokine functions. Proc. Nat. Acad. Sci. 87: 7732-7736, 1990. [PubMed: 2217207] [Full Text: https://doi.org/10.1073/pnas.87.19.7732]
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]
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]
Tekamp-Olson, P., Gallegos, C., Bauer, D., McClain, J., Sherry, B., Fabre, M., van Deventer, S., Cerami, A. Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. J. Exp. Med. 172: 911-919, 1990. [PubMed: 2201751] [Full Text: https://doi.org/10.1084/jem.172.3.911]
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]