CCL7
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| Location (UCSC) | Chr 17: 34.27 – 34.27 Mb | n/a | |||||||
| PubMed search | [2] | n/a | |||||||
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Chemokine (C-C motif) ligand 7 (CCL7) is a small
Genomics
In the human genome, CCL7 is encoded by the CCL7 gene which is one of the several chemokine genes clustered on chromosome 17q11.2-q12. This region contains the gene for the MCP subset of CC chemokines. The CCL7 gene has been given the locus symbol SCYA7.[4]
The gene consists of three exons and two introns. The first exon contains a 5′-untranslated region (5′-UTR), the information for the signal sequence (23 amino acids), and the mature protein's first two amino acids. The second exon encodes amino acids 3–42 of the mature proteins. The third exon is composed of the C-terminal region of the protein, a 3′-UTR containing one or more destabilizing AU-rich sequences and a polyadenylation signal.[5]
Molecular biology
CCL7 was first characterized from osteosarcoma supernatant.[6] CCL7 consists of 99 amino acids, which contains 23-amino acid signal peptide. The mature protein about 76 amino acids is secreted after cleavage of the signal peptide.[7] In contrast to most chemokines, CCL7 exists in a general monomeric form, differing from the dimer formed in a highly concentrated solution.[8][9]
CCL7 can exist in four different glycotypes with a molecular weight 11, 13, 17 and 18 kDa in COS cells.[5]
CCL7 mediates effects on the immune cell types through binding to numerous receptors, including CCR1, CCR2, CCR3, CCR5, and CCR10.[10][7] These receptors belongs to the G protein-coupled seven-transmembrane receptors.[11] CCL7 can also interact with cell surface glycosaminoglycans (GAGs) present on all animal cell surfaces.[12]
Function
CCL7 is expressed in many types of cells, including stromal cells, keratinocytes, airway smooth muscle cells, parenchymal cells, fibroblasts and leukocytes and also in tumor cells.[5][7][13]
CCL7 mainly acts as a
The speed of immune responses varies depending on the type of the cells. In epithelial cells, fibroblasts, and endothelial cells the response is immediate after the stimulation by proinflammatory cytokines as IL-1β and TNFα. In T lymphocytes the expression of CCL7 occurs after 3–5 days after the stimulation.[18]
CCL7 has been shown to interact with MMP2 by binding CCR2 receptor.[19]
Clinical importance
CCL7 is a multipotent chemokine involved in anti-bacterial, anti-viral and anti-fungal immune responses. For example, CCL7-mediated stimulation of CCR2 chemokine receptors on monocytes is participating in the elimination of
Diseases associated with CCL7 dysregulation are observed. For example, an abnormal increase of CCL7 worsens many disorders, like HIV or lesional psoriasis.[23][24] Furthermore, CCL7 is implicated in various immunological diseases, as ulcerative colitis, multiple sclerosis or nonatopic and atopic asthma.[12][25]
It seems, that the expression of CCL7 can activate an antitumor immune response.[17]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000108688 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 9242519.
- PMID 7916328.
- ^ PMID 10379912.
- PMID 1613466.
- ^ PMID 29915688.
- S2CID 24062093.
- PMID 9109648.
- PMID 26466066.
- S2CID 10579265.
- ^ PMID 11781181.
- PMID 10064085.
- S2CID 32126355.
- S2CID 25639109.
- PMID 17364026.
- ^ S2CID 36845889.
- S2CID 30184294.
- PMID 8461011.
- PMID 22244581.
- PMID 26401006.
- PMID 21252989.
- PMID 27321752.
- S2CID 2805402.
- PMID 12009564.
Further reading
- Menten P, Wuyts A, Van Damme J (2002). "Monocyte chemotactic protein-3". European Cytokine Network. 12 (4): 554–60. PMID 11781181.
- Van Damme J, Proost P, Lenaerts JP, Opdenakker G (July 1992). "Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family". The Journal of Experimental Medicine. 176 (1): 59–65. PMID 1613466.
- Ben-Baruch A, Xu L, Young PR, Bengali K, Oppenheim JJ, Wang JM (September 1995). "Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors. C-C CKR1, a receptor for macrophage inflammatory protein-1 alpha/Rantes, is also a functional receptor for MCP3". The Journal of Biological Chemistry. 270 (38): 22123–8. PMID 7545673.
- Opdenakker G, Fiten P, Nys G, Froyen G, Van Roy N, Speleman F, et al. (May 1994). "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 (2): 403–8. PMID 7916328.
- Minty A, Chalon P, Guillemot JC, Kaghad M, Liauzun P, Magazin M, et al. (1993). "Molecular cloning of the MCP-3 chemokine gene and regulation of its expression". European Cytokine Network. 4 (2): 99–110. PMID 8318676.
- Opdenakker G, Froyen G, Fiten P, Proost P, Van Damme J (March 1993). "Human monocyte chemotactic protein-3 (MCP-3): molecular cloning of the cDNA and comparison with other chemokines". Biochemical and Biophysical Research Communications. 191 (2): 535–42. PMID 8461011.
- Combadiere C, Ahuja SK, Van Damme J, Tiffany HL, Gao JL, Murphy PM (December 1995). "Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine receptors 1 and 2B". The Journal of Biological Chemistry. 270 (50): 29671–5. PMID 8530354.
- Power CA, Clemetson JM, Clemetson KJ, Wells TN (August 1995). "Chemokine and chemokine receptor mRNA expression in human platelets". Cytokine. 7 (6): 479–82. PMID 8580362.
- Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS (May 1996). "Cloning, expression, and characterization of the human eosinophil eotaxin receptor". The Journal of Experimental Medicine. 183 (5): 2349–54. PMID 8642344.
- Kim KS, Rajarathnam K, Clark-Lewis I, Sykes BD (October 1996). "Structural characterization of a monomeric chemokine: monocyte chemoattractant protein-3". FEBS Letters. 395 (2–3): 277–82. S2CID 24062093.
- Meunier S, Bernassau JM, Guillemot JC, Ferrara P, Darbon H (April 1997). "Determination of the three-dimensional structure of CC chemokine monocyte chemoattractant protein 3 by 1H two-dimensional NMR spectroscopy". Biochemistry. 36 (15): 4412–22. PMID 9109648.
- Polentarutti N, Introna M, Sozzani S, Mancinelli R, Mantovani G, Mantovani A (September 1997). "Expression of monocyte chemotactic protein-3 in human monocytes and endothelial cells". European Cytokine Network. 8 (3): 271–4. PMID 9346360.
- Bonini JA, Martin SK, Dralyuk F, Roe MW, Philipson LH, Steiner DF (October 1997). "Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3". DNA and Cell Biology. 16 (10): 1249–56. PMID 9364936.
- Nibbs RJ, Wylie SM, Yang J, Landau NR, Graham GJ (December 1997). "Cloning and characterization of a novel promiscuous human beta-chemokine receptor D6". The Journal of Biological Chemistry. 272 (51): 32078–83. PMID 9405404.
- Wang JM, Ueda H, Howard OM, Grimm MC, Chertov O, Gong X, et al. (October 1998). "HIV-1 envelope gp120 inhibits the monocyte response to chemokines through CD4 signal-dependent chemokine receptor down-regulation". Journal of Immunology. 161 (8): 4309–17. S2CID 27267900.
- Albini A, Ferrini S, Benelli R, Sforzini S, Giunciuglio D, Aluigi MG, et al. (October 1998). "HIV-1 Tat protein mimicry of chemokines". Proceedings of the National Academy of Sciences of the United States of America. 95 (22): 13153–8. PMID 9789057.
- Rabin RL, Park MK, Liao F, Swofford R, Stephany D, Farber JM (April 1999). "Chemokine receptor responses on T cells are achieved through regulation of both receptor expression and signaling". Journal of Immunology. 162 (7): 3840–50. S2CID 39401025.
- Wedemeyer J, Lorentz A, Göke M, Meier PN, Flemming P, Dahinden CA, et al. (May 1999). "Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa". Gut. 44 (5): 629–35. PMID 10205198.
- Blanpain C, Migeotte I, Lee B, Vakili J, Doranz BJ, Govaerts C, et al. (September 1999). "CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist". Blood. 94 (6): 1899–905. PMID 10477718.
- Jordan NJ, Kolios G, Abbot SE, Sinai MA, Thompson DA, Petraki K, Westwick J (October 1999). "Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells". The Journal of Clinical Investigation. 104 (8): 1061–9. PMID 10525044.
External links
- Human CCL7 genome location and CCL7 gene details page in the UCSC Genome Browser.
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