Wikipedia

CC chemokine receptors

CC chemokine receptors (or beta chemokine receptors) are integral membrane proteins that specifically bind and respond to cytokines of the CC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins since they span the cell membrane seven times. To date, ten true members of the CC chemokine receptor subfamily have been described. These are named CCR1 to CCR10 according to the IUIS/WHO Subcommittee on Chemokine Nomenclature.

CCR1
Identifiers
SymbolCCR1
NCBI gene1230
HGNC1602
OMIM601159
RefSeqNM_001295
UniProtP32246
Other data
LocusChr. 3 p21
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StructuresSwiss-model
DomainsInterPro
CCR2
Identifiers
SymbolCCR2
NCBI gene1231
HGNC1603
OMIM601268
PDB1KAD
RefSeqNM_000647
UniProtP41597
Other data
LocusChr. 3 p21
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StructuresSwiss-model
DomainsInterPro
CCR3
Identifiers
SymbolCCR3
NCBI gene1232
HGNC1604
OMIM601268
RefSeqNM_001837
UniProtP51677
Other data
LocusChr. 3 p21
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StructuresSwiss-model
DomainsInterPro
CCR4
Identifiers
SymbolCCR4
NCBI gene1233
HGNC1605
OMIM604836
RefSeqNM_005508
UniProtP51679
Other data
LocusChr. 3 p24
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StructuresSwiss-model
DomainsInterPro
CCR5
Identifiers
SymbolCCR5
NCBI gene1234
HGNC1606
OMIM601373
PDB1ND8
RefSeqNM_000579
UniProtP51681
Other data
LocusChr. 3 p21
Search for
StructuresSwiss-model
DomainsInterPro
CCR6
Identifiers
SymbolCCR6
NCBI gene1235
HGNC1607
OMIM601835
RefSeqNM_004367
UniProtP51684
Other data
LocusChr. 6 q27
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StructuresSwiss-model
DomainsInterPro
CCR7
Identifiers
SymbolCCR7
NCBI gene1236
HGNC1608
OMIM600242
RefSeqNM_001838
UniProtP32248
Other data
LocusChr. 17 q12-q21.2
Search for
StructuresSwiss-model
DomainsInterPro
CCR8
Identifiers
SymbolCCR8
NCBI gene1237
HGNC1609
OMIM601834
RefSeqNM_005201
UniProtP51685
Other data
LocusChr. 3 p22
Search for
StructuresSwiss-model
DomainsInterPro
CCR9
Identifiers
SymbolCCR9
NCBI gene10803
HGNC1610
OMIM604738
RefSeqNM_031200
UniProtP51686
Other data
LocusChr. 3 p21
Search for
StructuresSwiss-model
DomainsInterPro
CCR10
Identifiers
SymbolCCR10
NCBI gene2826
HGNC4474
OMIM600240
RefSeqNM_016602
UniProtP46092
Other data
LocusChr. 17 17q21.1-q21
Search for
StructuresSwiss-model
DomainsInterPro

Mechanism

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The CC chemokine receptors all work by activating the G protein Gi.[1]

Types

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Overview table

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Receptor Ligands
CCR1 CCL4, CCL5, CCL6, CCL14, CCL15, CCL16, CCL23
CCR2 CCL2, CCL8, CCL16
CCR3 CCL11, CCL26, CCL7, CCL13, CCL15, CCL24, CCL5, CCL28, CCL18
CCR4 CCL3, CCL5, CCL17, CCL22
CCR5 CCL3, CCL4, CCL5, CCL8, CCL11, CCL13, CCL14, CCL16
CCR6 CCL20
CCR7 CCL19, CCL21
CCR8 CCL1, CCL16
CCR9 CCL25
CCR10 CCL27, CCL28
CCR11 CCL19, CCL21, CCL25

CCR1

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CCR1 was the first CC chemokine receptor identified and binds multiple inflammatory/inducible (see inducible gene) CC chemokines (including CCL4, CCL5, CCL6, CCL14, CCL15, CCL16 and CCL23).[2][3][4] In humans, this receptor can be found on peripheral blood lymphocytes and monocytes. There is some suggestion that this chemokine receptor is restricted to memory T-cells within the lymphocyte pool. This receptor is also designated cluster of differentiation marker CD191.

CCR2

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CCR2 can interact with CCL2, CCL8 and CCL16 and has been identified on the surface of monocytes, activated memory T cells, B cells, and basophils in humans, and also in peritoneal macrophages in mice.[4][5] CCR2 is also designated CD192.

CCR3

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CCR3 is a receptor for multiple inflammatory/inducible CC chemokines, including CCL11, CCL26, CCL7, CCL13, CCL15, CCL24 and CCL5 that attract eosinophils, and CCL28 that attracts B and T lymphocytes to mucosal tissues.[3][6][7][8][9] It is most highly expressed in both eosinophils and basophils, but can also be found in Th1 and Th2 cells and airway epithelial cells. Thus CCR3 plays a role in allergic reactions. CCR3 is also known as CD193.

CCR4

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CCR4 is expressed on Th2 T lymphocytes and is up-regulated by T cell receptor activation. However, some reports suggest a role for this receptor also in trafficking of dendritic cells. The CC chemokines CCL3, CCL5, CCL17 and CCL22 signal through this receptor.[10][11]

CCR5

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CCR5 is expressed on several cell types including peripheral blood-derived dendritic cells, CD34+ hematopoietic progenitor cells and certain activated/memory Th1 lymphocytes. This receptor is well defined as a major coreceptor implicated in susceptibility to HIV-1 infection and disease. This receptor has several CC chemokine ligands including CCL2, CCL3, CCL4, CCL5, CCL11, CCL13, CCL14 and CCL16.[4][5][12][13]

CCR6

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CCR6, a receptor for CCL20, is expressed on unactivated memory T-cells and some dendritic cells. CCR6 is also expressed on Th17 cells.[14] CCR6 is down-regulated in activated T-cells.[15]

CCR7

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CCR7 is a highly important receptor with a role in trafficking of B and T lymphocytes and dendritic cells to and across high endothelial venules and positioning those cells correctly in T cell zones of secondary lymphoid organs. Its ligands include the related chemokines CCL19 and CCL21, (previously called ELC and SLC).[16]

CCR8

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CCR8 is associated with Th2 lymphocytes and is therefore found predominantly in the thymus (in humans) although some expression can be found in the brain, spleen, lymph node, and monocytes at the nucleotide level. The ligands for this receptor are CCL1 and CCL16[17]

CCR9

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CCR9 was previously called orphan receptor GPR 9-6 and is very highly expressed in thymus (on both immature and mature T-cells) while low in lymph nodes and spleen. CCR9 is also abundant in the gut, with its expression associated with T cells of the intestine. The specific ligand of this receptor is CCL25[18] To note, the chemokine binding protein D6 had previously been named CCR9, but this molecule is a scavenger receptor not a true (signaling) chemokine receptor.

CCR10

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CCR10 is receptor for CCL27 and CCL28 that was originally called orphan receptor GPR2.[8][19][20][21] CCR10 has been implicated in inflammation of the skin, and has been shown to recruit regulatory T cells (Tregs) to mucosal layers.

CCR11

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This molecule was originally designated CCR11 due to its ability to bind several CC chemokines (including CCL19, CCL21 and CCL25) and its structural similarity to chemokine receptors. However, due to the inability of this molecule (also known as CCRL1 and CCX CKR) to generate a signal following ligand interaction, it has been suggested that it is a scavenger receptor for chemokines and not a bona fide chemokine receptor. Thus CCRL1 should not be called CCR11 under the guidelines of the IUIS/WHO Subcommittee on Chemokine Nomenclature.

References

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  1. ^ senselab
  2. ^ Ma B, Zhu Z, Homer RJ, Gerard C, Strieter R, Elias JA (February 2004). "The C10/CCL6 chemokine and CCR1 play critical roles in the pathogenesis of IL-13-induced inflammation and remodeling". Journal of Immunology. 172 (3): 1872–81. doi:10.4049/jimmunol.172.3.1872. PMID 14734772.
  3. ^ a b Youn BS, Zhang SM, Lee EK, Park DH, Broxmeyer HE, Murphy PM, et al. (December 1997). "Molecular cloning of leukotactin-1: a novel human beta-chemokine, a chemoattractant for neutrophils, monocytes, and lymphocytes, and a potent agonist at CC chemokine receptors 1 and 3". Journal of Immunology. 159 (11): 5201–5. doi:10.4049/jimmunol.159.11.5201. PMID 9548457. S2CID 20622216.
  4. ^ a b c Nomiyama H, Hieshima K, Nakayama T, Sakaguchi T, Fujisawa R, Tanase S, et al. (August 2001). "Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes". International Immunology. 13 (8): 1021–9. doi:10.1093/intimm/13.8.1021. PMID 11470772.
  5. ^ a b Ogilvie P, Bardi G, Clark-Lewis I, Baggiolini M, Uguccioni M (April 2001). "Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5". Blood. 97 (7): 1920–4. doi:10.1182/blood.v97.7.1920. PMID 11264152.
  6. ^ Kitaura M, Suzuki N, Imai T, Takagi S, Suzuki R, Nakajima T, et al. (September 1999). "Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3". The Journal of Biological Chemistry. 274 (39): 27975–80. doi:10.1074/jbc.274.39.27975. PMID 10488147.
  7. ^ Kitaura M, Nakajima T, Imai T, Harada S, Combadiere C, Tiffany HL, et al. (March 1996). "Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3". The Journal of Biological Chemistry. 271 (13): 7725–30. doi:10.1074/jbc.271.13.7725. PMID 8631813.
  8. ^ a b Pan J, Kunkel EJ, Gosslar U, Lazarus N, Langdon P, Broadwell K, et al. (September 2000). "A novel chemokine ligand for CCR10 and CCR3 expressed by epithelial cells in mucosal tissues". Journal of Immunology. 165 (6): 2943–9. doi:10.4049/jimmunol.165.6.2943. PMID 10975800.
  9. ^ White JR, Imburgia C, Dul E, Appelbaum E, O'Donnell K, O'Shannessy DJ, et al. (November 1997). "Cloning and functional characterization of a novel human CC chemokine that binds to the CCR3 receptor and activates human eosinophils". Journal of Leukocyte Biology. 62 (5): 667–75. doi:10.1002/jlb.62.5.667. PMID 9365122. S2CID 12197497.
  10. ^ Imai T, Baba M, Nishimura M, Kakizaki M, Takagi S, Yoshie O (June 1997). "The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4". The Journal of Biological Chemistry. 272 (23): 15036–42. doi:10.1074/jbc.272.23.15036. PMID 9169480.
  11. ^ Imai T, Chantry D, Raport CJ, Wood CL, Nishimura M, Godiska R, et al. (January 1998). "Macrophage-derived chemokine is a functional ligand for the CC chemokine receptor 4". The Journal of Biological Chemistry. 273 (3): 1764–8. doi:10.1074/jbc.273.3.1764. PMID 9430724.
  12. ^ Gong W, Howard OM, Turpin JA, Grimm MC, Ueda H, Gray PW, et al. (February 1998). "Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication". The Journal of Biological Chemistry. 273 (8): 4289–92. doi:10.1074/jbc.273.8.4289. PMID 9468473.
  13. ^ 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. doi:10.1182/blood.V94.6.1899. PMID 10477718.
  14. ^ Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, et al. (June 2007). "Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells". Nature Immunology. 8 (6): 639–46. doi:10.1038/ni1467. PMID 17486092. S2CID 21824460.
  15. ^ Baba M, Imai T, Nishimura M, Kakizaki M, Takagi S, Hieshima K, et al. (June 1997). "Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC". The Journal of Biological Chemistry. 272 (23): 14893–8. doi:10.1074/jbc.272.23.14893. PMID 9169459.
  16. ^ Yoshida R, Imai T, Hieshima K, Kusuda J, Baba M, Kitaura M, et al. (May 1997). "Molecular cloning of a novel human CC chemokine EBI1-ligand chemokine that is a specific functional ligand for EBI1, CCR7". The Journal of Biological Chemistry. 272 (21): 13803–9. doi:10.1074/jbc.272.21.13803. PMID 9153236.
  17. ^ Roos RS, Loetscher M, Legler DF, Clark-Lewis I, Baggiolini M, Moser B (July 1997). "Identification of CCR8, the receptor for the human CC chemokine I-309". The Journal of Biological Chemistry. 272 (28): 17251–4. doi:10.1074/jbc.272.28.17251. PMID 9211859.
  18. ^ Zaballos A, Gutiérrez J, Varona R, Ardavín C, Márquez G (May 1999). "Cutting edge: identification of the orphan chemokine receptor GPR-9-6 as CCR9, the receptor for the chemokine TECK". Journal of Immunology. 162 (10): 5671–5. doi:10.4049/jimmunol.162.10.5671. PMID 10229797. S2CID 21522407.
  19. ^ Gosling J, Dairaghi DJ, Wang Y, Hanley M, Talbot D, Miao Z, Schall TJ (March 2000). "Cutting edge: identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK". Journal of Immunology. 164 (6): 2851–6. doi:10.4049/jimmunol.164.6.2851. PMID 10706668.
  20. ^ Homey B, Wang W, Soto H, Buchanan ME, Wiesenborn A, Catron D, et al. (April 2000). "Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC)". Journal of Immunology. 164 (7): 3465–70. doi:10.4049/jimmunol.164.7.3465. PMID 10725697.
  21. ^ Wang W, Soto H, Oldham ER, Buchanan ME, Homey B, Catron D, et al. (July 2000). "Identification of a novel chemokine (CCL28), which binds CCR10 (GPR2)". The Journal of Biological Chemistry. 275 (29): 22313–23. doi:10.1074/jbc.M001461200. PMID 10781587.
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  • "Chemokine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2008-11-25.
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