Chemokine (C-C motif) ligand 8 (CCL8), also known as monocyte chemoattractant protein 2 (MCP2), is a protein that in humans is encoded by the CCL8 gene.[3][4]

CCL8
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesCCL8, HC14, MCP-2, MCP2, SCYA10, SCYA8, C-C motif chemokine ligand 8
External IDsOMIM: 602283; HomoloGene: 48362; GeneCards: CCL8; OMA:CCL8 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005623

n/a

RefSeq (protein)

NP_005614

n/a

Location (UCSC)Chr 17: 34.32 – 34.32 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

CCL8 is a small cytokine belonging to the CC chemokine family. The CCL8 protein is produced as a precursor containing 109 amino acids, which is cleaved to produce mature CCL8 containing 75 amino acids. The gene for CCL8 is encoded by 3 exons and is located within a large cluster of CC chemokines on chromosome 17q11.2 in humans.[4][5] MCP-2 is chemotactic for and activates many different immune cells, including mast cells, eosinophils and basophils, (that are implicated in allergic responses), and monocytes, T cells, and NK cells that are involved in the inflammatory response.[6][7] CCL8 elicits its effects by binding to several different cell surface receptors called chemokine receptors. These receptors include CCR1, CCR2B, CCR3 and CCR5.[7][8]

CCL8 is a CC chemokine that utilizes multiple cellular receptors to attract and activate human leukocytes. CCL8 is a potent inhibitor of HIV1 by virtue of its high-affinity binding to the receptor CCR5, one of the major co-receptors for HIV1.[9] In addition, CCL8 attributes to the growth of metastasis in breast cancer cells. The manipulation of this chemokine activity influences the histology of tumors promoting steps of metastatic processes.[10] CCL8 is also involved in attracting macrophages to the decidua in labor.[11]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000108700Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Entrez Gene: chemokine (C-C motif) ligand 8".
  4. ^ a b Van Coillie E, Fiten P, Nomiyama H, Sakaki Y, Miura R, Yoshie O, Van Damme J, Opdenakker G (March 1997). "The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2". Genomics. 40 (2): 323–31. doi:10.1006/geno.1996.4594. PMID 9119400.
  5. ^ 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". J. Exp. Med. 176 (1): 59–65. doi:10.1084/jem.176.1.59. PMC 2119277. PMID 1613466.
  6. ^ Proost P, Wuyts A, Van Damme J (January 1996). "Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1". J. Leukoc. Biol. 59 (1): 67–74. doi:10.1002/jlb.59.1.67. PMID 8558070. S2CID 30445255.
  7. ^ a b Gong W, Howard OM, Turpin JA, Grimm MC, Ueda H, Gray PW, Raport CJ, Oppenheim JJ, Wang JM (February 1998). "Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication". J. Biol. Chem. 273 (8): 4289–92. doi:10.1074/jbc.273.8.4289. PMID 9468473.
  8. ^ Ge B, Li J, Wei Z, Sun T, Song Y, Khan NU (2017). "Functional expression of CCL8 and its interaction with chemokine receptor CCR3". BMC Immunol. 18 (1): 54. doi:10.1186/s12865-017-0237-5. PMC 5745793. PMID 29281969.
  9. ^ PDB: 1ESR​; Blaszczyk J, Coillie EV, Proost P, Damme JV, Opdenakker G, Bujacz GD, Wang JM, Ji X (November 2000). "Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors". Biochemistry. 39 (46): 14075–81. doi:10.1021/bi0009340. PMID 11087354.
  10. ^ Farmaki E, Chatzistamou I, Kaza V, Kiaris H (2016). "A CCL8 gradient drives breast cancer cell dissemination". Oncogene. 35 (49): 6309–6318. doi:10.1038/onc.2016.161. PMC 5112152. PMID 27181207.
  11. ^ Hamilton SA, Tower CL, Jones RL (2013). "Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour". PLOS ONE. 8 (2): e56946. Bibcode:2013PLoSO...856946H. doi:10.1371/journal.pone.0056946. PMC 3579936. PMID 23451115.
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Further reading

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