Alternative titles; symbols
HGNC Approved Gene Symbol: CXCL5
Cytogenetic location: 4q13.3 Genomic coordinates (GRCh38): 4:73,995,642-73,998,677 (from NCBI)
Epithelial cell-derived neutrophil-activating peptide ENA78 is an inflammatory chemokine that is produced concomitantly with interleukin-8 (IL8; 146930) in response to stimulation with either interleukin-1 (IL1B; 147720) or tumor necrosis factor-alpha (TNFA; 191160). Chang et al. (1994) identified a full-length ENA78 cDNA and isolated its genomic clone.
Rovai et al. (1997) cloned the human ENA78 gene (which is also symbolized SCYB5) as well as GCP2 (SCYB6; 138965). 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. 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.
Chang et al. (1994) determined that the ENA78 gene consists of 4 exons and 3 introns, with a structure resembling that of the IL8 gene. The transcriptional initiation site was mapped to a position 96 bp upstream from the translation initiation site.
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).
By PCR analysis and mapping of YAC clones, O'Donovan et al. (1999) localized a number of CXC chemokine genes to chromosome 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 (601704)--telomere. The SCYB5 gene was localized to 4q12-q13.
By fluorescence in situ hybridization, Chang et al. (1994) mapped the ENA78 gene to 4q13-q21, the same region to which several other inflammatory cytokine genes have been mapped. Chang et al. (1994) found that even though the ENA78 and IL8 genes share great similarity in genomic structure and chromosome location, they appear to be regulated by different mechanisms.
Chang, M., McNinch, J., Basu, R., Simonet, S. Cloning and characterization of the human neutrophil-activating peptide (ENA-78) gene. J. Biol. Chem. 269: 25277-25282, 1994. [PubMed: 7929219]
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]
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]
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]