CCL8

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 PDB Human UniProt search: PDBe RCSB List of PDB id codes 1ESR
Identifiers
Aliases	CCL8, HC14, MCP-2, MCP2, SCYA10, SCYA8, C-C motif chemokine ligand 8
External IDs	OMIM: 602283 HomoloGene: 48362 GeneCards: CCL8
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q12 Start 34,319,435 bp[1] End 34,321,402 bp[1]
Gene ontology Molecular function • protein kinase activity • cytokine activity • heparin binding • phospholipase activator activity • CCR chemokine receptor binding • chemokine activity • GO:0001948 protein binding • CCR2 chemokine receptor binding Cellular component • extracellular region • cell • extracellular Biological process • G-protein coupled receptor signaling pathway • monocyte chemotaxis • chemokine-mediated signaling pathway • cellular response to tumor necrosis factor • cell-cell signaling • response to virus • cellular calcium ion homeostasis • neutrophil chemotaxis • chemotaxis • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • cellular response to interleukin-1 • immune response • positive regulation of ERK1 and ERK2 cascade • cellular response to interferon-gamma • lymphocyte chemotaxis • inflammatory response • calcium ion transport • signal transduction • exocytosis • protein phosphorylation • antimicrobial humoral immune response mediated by antimicrobial peptide • positive regulation of leukocyte migration • negative regulation of leukocyte proliferation • regulation of receptor activity • angiogenesis • eosinophil chemotaxis 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	[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

1. GRCh38: Ensembl release 89: ENSG00000108700 - Ensembl, 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. 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. PMID 8558070.
7. 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: 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: 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: e56946. doi:10.1371/journal.pone.0056946. PMC 3579936. PMID 23451115.

External links

• Human CCL8 genome location and CCL8 gene details page in the UCSC Genome Browser.

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. PMC 5301077. 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. PMC 4829203. 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.