CCL8

Chemokine (C-C motif) ligand 8
Crystallographic structure of human C-C motif chemokine 8.[1]
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1ESR​
Identifiers
Symbols	CCL8 ; HC14; MCP-2; MCP2; SCYA10; SCYA8
External IDs	OMIM: 602283 HomoloGene: 48362 GeneCards: CCL8 Gene
Gene ontology Molecular function • protein kinase activity • chemokine activity • heparin binding • phospholipase activator activity • CCR chemokine receptor binding Cellular component • extracellular space • cell Biological process • monocyte chemotaxis • positive regulation of leukocyte migration • protein phosphorylation • calcium ion transport • cellular calcium ion homeostasis • exocytosis • chemotaxis • inflammatory response • signal transduction • G-protein coupled receptor signaling pathway • cell-cell signaling • response to virus • neutrophil chemotaxis • positive regulation of GTPase activity • eosinophil chemotaxis • lymphocyte chemotaxis • chemokine-mediated signaling pathway • positive regulation of ERK1 and ERK2 cascade • negative regulation of leukocyte proliferation • cellular response to interferon-gamma • cellular response to interleukin-1 • cellular response to tumor necrosis factor Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6355	n/a
Ensembl	ENSG00000108700	n/a
UniProt	P80075	n/a
RefSeq (mRNA)	NM_005623	n/a
RefSeq (protein)	NP_005614	n/a
Location (UCSC)	Chr 17: 34.32 – 34.32 Mb	n/a
PubMed search		n/a

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.^[2][3]

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.^[3][4] MCP-2 is chemotactic for and activates a 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.^[5][6] CCL8 elicits its effects by binding to several different cell surface receptors called chemokine receptors. These receptors include CCR1, CCR2B and CCR5.^[6]

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.^[1]

References

1. 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.
2. "Entrez Gene: chemokine (C-C motif) ligand 8".
3. 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.
4. 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.
5. 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. PMID 8558070.
6. 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.

Further reading

• Struyf S, Proost P, Vandercappellen J; et al. (2009). "Synergistic up-regulation of MCP-2/CCL8 activity is counteracted by chemokine cleavage, limiting its inflammatory and anti-tumoral effects.". Eur. J. Immunol. 39 (3): 843–57. doi:10.1002/eji.200838660. PMID 19224633.
• Rom S, Rom I, Passiatore G; et al. (2010). "CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells.". FASEB J. 24 (7): 2292–300. doi:10.1096/fj.09-143503. PMC 2887261. PMID 20181935.
• Menon R, Pearce B, Velez DR; et al. (2009). "Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants.". Reprod. Biol. Endocrinol. 7: 62. doi:10.1186/1477-7827-7-62. PMC 2714850. PMID 19527514.
• Segat L, Brandão LA, Guimarães RL; et al. (2010). "Polymorphisms in innate immunity genes and patients response to dendritic cell-based HIV immuno-treatment.". Vaccine 28 (10): 2201–6. doi:10.1016/j.vaccine.2009.12.056. PMID 20056178.
• Rajaraman P, Brenner AV, Butler MA; et al. (2009). "Common variation in genes related to innate immunity and risk of adult glioma.". Cancer Epidemiol. Biomarkers Prev. 18 (5): 1651–8. doi:10.1158/1055-9965.EPI-08-1041. PMC 2771723. PMID 19423540.
• Han S, Lan Q, Park AK; et al. (2010). "Polymorphisms in innate immunity genes and risk of childhood leukemia.". Hum. Immunol. 71 (7): 727–30. doi:10.1016/j.humimm.2010.04.004. PMC 2967770. PMID 20438785.
• Velez DR, Fortunato SJ, Thorsen P; et al. (2008). "Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants.". PLoS ONE 3 (9): e3283. doi:10.1371/journal.pone.0003283. PMC 2553267. PMID 18818748.
• Villa C, Venturelli E, Fenoglio C; et al. (2009). "CCL8/MCP-2 association analysis in patients with Alzheimer's disease and frontotemporal lobar degeneration.". J. Neurol. 256 (8): 1379–81. doi:10.1007/s00415-009-5138-y. PMID 19415413.
• Siezen CL, Bont L, Hodemaekers HM; et al. (2009). "Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes.". Pediatr. Infect. Dis. J. 28 (4): 333–5. doi:10.1097/INF.0b013e31818e2aa9. PMID 19258923.
• Vyshkina T, Sylvester A, Sadiq S; et al. (2008). "CCL genes in multiple sclerosis and systemic lupus erythematosus.". J. Neuroimmunol. 200 (1-2): 145–52. doi:10.1016/j.jneuroim.2008.05.016. PMID 18602166.
• Ruhwald M, Bodmer T, Maier C; et al. (2008). "Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis.". Eur. Respir. J. 32 (6): 1607–15. doi:10.1183/09031936.00055508. PMID 18684849.
• Skibola CF, Bracci PM, Halperin E; et al. (2008). "Polymorphisms in the estrogen receptor 1 and vitamin C and matrix metalloproteinase gene families are associated with susceptibility to lymphoma.". PLoS ONE 3 (7): e2816. doi:10.1371/journal.pone.0002816. PMC 2474696. PMID 18636124.
• Ockinger J, Stridh P, Beyeen AD; et al. (2010). "Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis.". Genes Immun. 11 (2): 142–54. doi:10.1038/gene.2009.82. PMID 19865101.
• Xie Z, Zhang J, Wu J; et al. (2008). "Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes.". Diabetes 57 (12): 3222–30. doi:10.2337/db08-0610. PMC 2584127. PMID 18835932.
• Rajaraman P, Brenner AV, Neta G; et al. (2010). "Risk of meningioma and common variation in genes related to innate immunity.". Cancer Epidemiol. Biomarkers Prev. 19 (5): 1356–61. doi:10.1158/1055-9965.EPI-09-1151. PMC 3169167. PMID 20406964.
• Velez DR, Fortunato S, Thorsen P; et al. (2009). "Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants.". Am. J. Obstet. Gynecol. 200 (2): 209.e1–27. doi:10.1016/j.ajog.2008.08.051. PMID 19019335.
• Dean RA, Cox JH, Bellac CL; et al. (2008). "Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+ CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx.". Blood 112 (8): 3455–64. doi:10.1182/blood-2007-12-129080. PMID 18660381.
• Hori T, Naishiro Y, Sohma H; et al. (2008). "CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease.". Blood 111 (8): 4403–12. doi:10.1182/blood-2007-06-097287. PMC 2288733. PMID 18256320.
• Schuurhof A, Bont L, Siezen CL; et al. (2010). "Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls.". Pediatr. Pulmonol. 45 (6): 608–13. doi:10.1002/ppul.21229. PMID 20503287.