CCR3 (gene) explained

C-C chemokine receptor type 3 is a protein that in humans is encoded by the CCR3 gene.^[1]

CCR3 has also recently been designated CD193 (cluster of differentiation 193).

Function

The protein encoded by this gene is a receptor for C-C type chemokines. It belongs to family 1 of the G protein-coupled receptors. This receptor binds and responds to a variety of chemokines, including eotaxin (CCL11), eotaxin-3 (CCL26), MCP-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5). It is highly expressed in eosinophils and basophils,^[2] and is also detected in TH1 and TH2 cells, as well as in airway epithelial cells. This receptor may contribute to the accumulation and activation of eosinophils and other inflammatory cells in the allergic airway, and possibly at sites of parasitic infection. It is also known to be an entry co-receptor for HIV-1, enabling viral infection in cells that also express CD4, the receptor of HIV-1.^[3] This gene and seven other chemokine receptor genes form a chemokine receptor gene cluster on the chromosomal region 3p21. Alternatively spliced transcript variants encoding the same protein have been described.^[1]

See also

• Cluster of differentiation

Interactions

CCR3 (gene) has been shown to interact with CCL5.^{[4] [5] [6]}

Further reading

• Choe H, Martin KA, Farzan M, Sodroski J, Gerard NP, Gerard C . Structural interactions between chemokine receptors, gp120 Env and CD4 . Semin. Immunol. . 10 . 3 . 249–57 . 1998 . 9653051 . 10.1006/smim.1998.0127 .
• Marone G, Florio G, Petraroli A, de Paulis A . Dysregulation of the IgE/Fc epsilon RI network in HIV-1 infection . J. Allergy Clin. Immunol. . 107 . 1 . 22–30 . 2001 . 11149986 . 10.1067/mai.2001.111589 . free .
• Marone G, Florio G, Triggiani M, Petraroli A, de Paulis A . Mechanisms of IgE elevation in HIV-1 infection . Crit. Rev. Immunol. . 20 . 6 . 477–96 . 2001 . 11396683 . 10.1615/critrevimmunol.v20.i6.40 .
• Ruibal-Ares BH, Belmonte L, Baré PC, Parodi CM, Massud I, de Bracco MM . HIV-1 infection and chemokine receptor modulation . Curr. HIV Res. . 2 . 1 . 39–50 . 2004 . 15053339 . 10.2174/1570162043484997 .
• Post TW, Bozic CR, Rothenberg ME, Luster AD, Gerard N, Gerard C . Molecular characterization of two murine eosinophil beta chemokine receptors . J. Immunol. . 155 . 11 . 5299–305 . 1995 . 10.4049/jimmunol.155.11.5299 . 7594543 . 12074627 .
• Combadiere C, Ahuja SK, Murphy PM . Cloning and functional expression of a human eosinophil CC chemokine receptor . J. Biol. Chem. . 270 . 28 . 16491–4 . 1995 . 7622448 . 10.1074/jbc.270.28.16491 . free .
• Ponath PD, Qin S, Ringler DJ, Clark-Lewis I, Wang J, Kassam N, Smith H, Shi X, Gonzalo JA, Newman W, Gutierrez-Ramos JC, Mackay CR . Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils . J. Clin. Invest. . 97 . 3 . 604–12 . 1996 . 8609214 . 507095 . 10.1172/JCI118456 .
• Kitaura M, Nakajima T, Imai T, Harada S, Combadiere C, Tiffany HL, Murphy PM, Yoshie O . Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3 . J. Biol. Chem. . 271 . 13 . 7725–30 . 1996 . 8631813 . 10.1074/jbc.271.13.7725 . free .
• Combadiere C, Ahuja SK, Murphy PM . Cloning and functional expression of a human eosinophil CC chemokine receptor . J. Biol. Chem. . 271 . 18 . 11034 . 1996 . 10.1016/S0021-9258(18)98113-5 . 8631926 . free .
• Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS . Cloning, expression, and characterization of the human eosinophil eotaxin receptor . J. Exp. Med. . 183 . 5 . 2349–54 . 1996 . 8642344 . 2192548 . 10.1084/jem.183.5.2349 .
• Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, Gerard N, Gerard C, Sodroski J . The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates . Cell . 85 . 7 . 1135–48 . 1996 . 8674119 . 10.1016/S0092-8674(00)81313-6 . 16198200 . free .
• Ponath PD, Qin S, Post TW, Wang J, Wu L, Gerard NP, Newman W, Gerard C, Mackay CR . Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils . J. Exp. Med. . 183 . 6 . 2437–48 . 1996 . 8676064 . 2192612 . 10.1084/jem.183.6.2437 .
• Samson M, Soularue P, Vassart G, Parmentier M . The genes encoding the human CC-chemokine receptors CC-CKR1 to CC-CKR5 (CMKBR1-CMKBR5) are clustered in the p21.3-p24 region of chromosome 3 . Genomics . 36 . 3 . 522–6 . 1997 . 8884276 . 10.1006/geno.1996.0498 .
• Heath H, Qin S, Rao P, Wu L, LaRosa G, Kassam N, Ponath PD, Mackay CR . Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody . J. Clin. Invest. . 99 . 2 . 178–84 . 1997 . 9005985 . 507784 . 10.1172/JCI119145 .
• He J, Chen Y, Farzan M, Choe H, Ohagen A, Gartner S, Busciglio J, Yang X, Hofmann W, Newman W, Mackay CR, Sodroski J, Gabuzda D . CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia . Nature . 385 . 6617 . 645–9 . 1997 . 9024664 . 10.1038/385645a0 . 1997Natur.385..645H . 4281639 .
• Daugherty BL, Springer MS . The beta-chemokine receptor genes CCR1 (CMKBR1), CCR2 (CMKBR2), and CCR3 (CMKBR3) cluster within 285 kb on human chromosome 3p21 . Genomics . 41 . 2 . 294–5 . 1997 . 9143512 . 10.1006/geno.1997.4626 .
• Forssmann U, Uguccioni M, Loetscher P, Dahinden CA, Langen H, Thelen M, Baggiolini M . Eotaxin-2, a novel CC chemokine that is selective for the chemokine receptor CCR3, and acts like eotaxin on human eosinophil and basophil leukocytes . J. Exp. Med. . 185 . 12 . 2171–6 . 1997 . 9182688 . 2196360 . 10.1084/jem.185.12.2171 .
• Alkhatib G, Berger EA, Murphy PM, Pease JE . Determinants of HIV-1 coreceptor function on CC chemokine receptor 3. Importance of both extracellular and transmembrane/cytoplasmic regions . J. Biol. Chem. . 272 . 33 . 20420–6 . 1997 . 9252350 . 10.1074/jbc.272.33.20420 . free .
• Pakianathan DR, Kuta EG, Artis DR, Skelton NJ, Hébert CA . Distinct but overlapping epitopes for the interaction of a CC-chemokine with CCR1, CCR3 and CCR5 . Biochemistry . 36 . 32 . 9642–8 . 1997 . 9289016 . 10.1021/bi970593z .
• Sallusto F, Mackay CR, Lanzavecchia A . Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells . Science . 277 . 5334 . 2005–7 . 1997 . 9302298 . 10.1126/science.277.5334.2005 .

External links

• Web site: Chemokine Receptors: CCR3 . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-11-25 . 2008-06-07 . https://web.archive.org/web/20080607150527/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2224 . dead .

Notes and References

1. Web site: Entrez Gene: CCR3 chemokine (C-C motif) receptor 3.
2. •Murphy KM, P Travers, M Walport (Eds.) (2010) Janeway's Immunobiology. 8th Edition. New York:Taylor & Francis, Inc.
3. Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, Gerard N, Gerard C, Sodroski J. 1996. Cell. 85. 7. 1135–1148. 10.1016/s0092-8674(00)81313-6. 8674119. 6. free. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates.
4. Ponath PD, Qin S, Post TW, Wang J, Wu L, Gerard NP, Newman W, Gerard C, Mackay CR . Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils . J. Exp. Med. . 1996 . 183 . 6 . 2437–48 . 8676064 . 2192612 . 10.1084/jem.183.6.2437 .
5. Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS . Cloning, expression, and characterization of the human eosinophil eotaxin receptor . J. Exp. Med. . 183 . 5 . 2349–54 . May 1996 . 8642344 . 2192548 . 10.1084/jem.183.5.2349 .
6. Struyf S, Menten P, Lenaerts JP, Put W, D'Haese A, De Clercq E, Schols D, Proost P, Van Damme J . Diverging binding capacities of natural LD78beta isoforms of macrophage inflammatory protein-1alpha to the CC chemokine receptors 1, 3 and 5 affect their anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils . Eur. J. Immunol. . 31 . 7 . 2170–8 . July 2001 . 11449371 . 10.1002/1521-4141(200107)31:7<2170::aid-immu2170>3.0.co;2-d . free .