Alternative titles; symbols
HGNC Approved Gene Symbol: CCL7
Cytogenetic location: 17q12 Genomic coordinates (GRCh38): 17:34,270,221-34,272,242 (from NCBI)
Chemokines are generally subdivided into C-C chemokines, which have 2 adjacent cysteines, and C-X-C chemokines, in which the cysteines are separated by 1 amino acid. Members of the former subfamily predominantly attract monocytes/macrophages, whereas the latter family consists of neutrophil chemotactic proteins. CCL7, also known as MCP3, belongs to the C-C chemokine family. Other members of the C-C chemokine family include MCP1 (CCL2; 158105), SCYA5 (CCL5; 187011), MIP1A (CCL3; 182283), SCYA1 (CCL1; 182281), and SCYA4 (CCL4; 182284), all of which are located with CCL7 in a gene cluster on chromosome 17q.
Monocyte chemotactic proteins (MCPs) are chemokines involved in macrophage recruitment during inflammation and cancer invasion (Mantovani et al., 1992). These factors are often produced by invasive cancer cells. Recruitment of leukocytes to the invasion front and stimulation of the secretion of invasion-promoting proteolytic enzymes from the attracted leukocytes may contribute to invasion and metastasis of tumor cells (Opdenakker and Van Damme, 1992). Opdenakker et al. (1994) used a full-length cDNA for MCP3, also known as SCYA7, to isolate the functional human MCP3 gene. Opdenakker et al. (1994) determined the sequence of the MCP3 gene.
Tissue degradation by the matrix metalloproteinase gelatinase A (120360) is pivotal to inflammation and metastasis. Recognizing the catalytic importance of substrate-binding exosites outside the catalytic domain, McQuibban et al. (2000) screened for extracellular substrates using the gelatinase A hemopexin domain as bait in the yeast 2-hybrid system. MCP3 was identified as a physiologic substrate of gelatinase A. Cleaved MCP3 binds to CC-chemokine receptors-1 (601159), -2 (601267), and -3 (601268), but no longer induces calcium fluxes or promotes chemotaxis, and instead acts as a general chemokine antagonist that dampens inflammation. McQuibban et al. (2000) suggested that matrix metalloproteinases are both effectors and regulators of the inflammatory response.
Using dermal fibroblasts from patients with systemic sclerosis (181750) and controls and from type-1 tight-skin (Tsk1) mice, Ong et al. (2003) demonstrated overexpression of MCP3 in early-stage systemic sclerosis and neonatal Tsk1 skin. Pro-alpha-2(I) collagen (COL1A2; 120160) promoter-reporter gene constructs were activated by MCP3 in transgenic mice and in transient transfection assays; the effects of MCP3 could be diminished by a neutralizing antibody to transforming growth factor-beta (TGFB1; 190180). Ong et al. (2003) concluded that MCP3 may operate as a profibrotic mediator with the potential to activate gene expression in the extracellular matrix, at least in part via induction of TGFB1, in addition to promoting an inflammatory cellular response.
By fluorescence in situ hybridization, Opdenakker et al. (1994) mapped the MCP3 gene to chromosome 17q11.2-q12.
Modi et al. (2003) genotyped 9 SNPs spanning the CCL2-CCL7-CCL11 (601156) gene cluster on chromosome 17q in more than 3,000 DNA samples from 5 AIDS cohorts (see 609423). Extensive linkage disequilibrium was observed, particularly for 3 SNPs, -2136T in the CCL2 promoter (158105.0001), 767G in intron 1 of the CCL2 gene (158105.0002), and -1385A in the CCL11 promoter (601156.0001), that formed a 31-kb haplotype (H7) containing the 3 genes. The frequencies of these 3 SNPs and the H7 haplotype were significantly elevated in uninfected individuals repeatedly exposed to HIV-1 through high-risk sexual behavior or contaminated blood products. Since these chemokines do not bind the primary HIV-1 coreceptors CCR5 (601373) or CXCR4 (162643), Modi et al. (2003) proposed that the influence of the H7 haplotype on HIV-1 transmission may result from activation of the immune system rather than receptor blockage.
Mantovani, A., Bottazzi, B., Colotta, F., Sozzani, S., Ruco, L. The origin and function of tumor-associated macrophages. Immun. Today 13: 265-270, 1992. [PubMed: 1388654] [Full Text: https://doi.org/10.1016/0167-5699(92)90008-U]
McQuibban, G. A., Gong, J.-H., Tam, E. M., McCulloch, C. A. G., Clark-Lewis, I., Overall, C. M. Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 289: 1202-1206, 2000. [PubMed: 10947989] [Full Text: https://doi.org/10.1126/science.289.5482.1202]
Modi, W. S., Goedert, J. J., Strathdee, S., Buchbinder, S., Detels, R., Donfield, S., O'Brien, S. J., Winkler, C. MCP-1-MCP-3-eotaxin gene cluster influences HIV-1 transmission. AIDS 17: 2357-2365, 2003. [PubMed: 14571188] [Full Text: https://doi.org/10.1097/00002030-200311070-00011]
Ong, V. H., Evans, L. A., Shiwen, X., Fisher, I. B., Rajkumar, V., Abraham, D. J., Black, C. M., Denton, C. P. Monocyte chemoattractant protein 3 as a mediator of fibrosis: overexpression in systemic sclerosis and the type 1 tight-skin mouse. Arthritis Rheum. 48: 1979-1991, 2003. [PubMed: 12847692] [Full Text: https://doi.org/10.1002/art.11164]
Opdenakker, G., Fiten, P., Nys, G., Froyen, G., Van Roy, N., Speleman, G., Laureys, G., Van Damme, J. The human MCP-3 gene (SCYA7): cloning, sequence analysis, and assignment to the C-C chemokine gene cluster on chromosome 17q11.2-q12. Genomics 21: 403-408, 1994. [PubMed: 7916328] [Full Text: https://doi.org/10.1006/geno.1994.1283]
Opdenakker, G., Van Damme, J. Chemotactic factors, passive invasion and metastasis of cancer cells. (Letter) Immun. Today 13: 463-464, 1992. [PubMed: 1298279] [Full Text: https://doi.org/10.1016/0167-5699(92)90079-M]