CC chemokine receptors

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CCR1
Identifiers
SymbolCCR1
NCBI gene 1230
HGNC 1602
OMIM 601159
RefSeq NM_001295
UniProt P32246
Other data
Locus Chr. 3 p21
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Structures Swiss-model
Domains InterPro
CCR2
Identifiers
SymbolCCR2
NCBI gene 1231
HGNC 1603
OMIM 601268
PDB 1KAD
RefSeq NM_000647
UniProt P41597
Other data
Locus Chr. 3 p21
Search for
Structures Swiss-model
Domains InterPro
CCR3
Identifiers
SymbolCCR3
NCBI gene 1232
HGNC 1604
OMIM 601268
RefSeq NM_001837
UniProt P51677
Other data
Locus Chr. 3 p21
Search for
Structures Swiss-model
Domains InterPro
CCR4
Identifiers
SymbolCCR4
NCBI gene 1233
HGNC 1605
OMIM 604836
RefSeq NM_005508
UniProt P51679
Other data
Locus Chr. 3 p24
Search for
Structures Swiss-model
Domains InterPro
CCR5
Identifiers
SymbolCCR5
NCBI gene 1234
HGNC 1606
OMIM 601373
PDB 1ND8
RefSeq NM_000579
UniProt P51681
Other data
Locus Chr. 3 p21
Search for
Structures Swiss-model
Domains InterPro
CCR6
Identifiers
SymbolCCR6
NCBI gene 1235
HGNC 1607
OMIM 601835
RefSeq NM_004367
UniProt P51684
Other data
Locus Chr. 6 q27
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Structures Swiss-model
Domains InterPro
CCR7
Identifiers
SymbolCCR7
NCBI gene 1236
HGNC 1608
OMIM 600242
RefSeq NM_001838
UniProt P32248
Other data
Locus Chr. 17 q12-q21.2
Search for
Structures Swiss-model
Domains InterPro
CCR8
Identifiers
SymbolCCR8
NCBI gene 1237
HGNC 1609
OMIM 601834
RefSeq NM_005201
UniProt P51685
Other data
Locus Chr. 3 p22
Search for
Structures Swiss-model
Domains InterPro
CCR9
Identifiers
SymbolCCR9
NCBI gene 10803
HGNC 1610
OMIM 604738
RefSeq NM_031200
UniProt P51686
Other data
Locus Chr. 3 p21
Search for
Structures Swiss-model
Domains InterPro
CCR10
Identifiers
SymbolCCR10
NCBI gene 2826
HGNC 4474
OMIM 600240
RefSeq NM_016602
UniProt P46092
Other data
Locus Chr. 17 17q21.1-q21
Search for
Structures Swiss-model
Domains InterPro

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.

Contents

Mechanism

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

Types

Overview table

ReceptorLigands
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

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

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

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

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

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

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

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

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

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

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

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.

Related Research Articles

<span class="mw-page-title-main">Chemokine</span> Small cytokines or signaling proteins secreted by cells

Chemokines, or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.

<span class="mw-page-title-main">CCL5</span> Mammalian protein found in Homo sapiens

Chemokine ligand 5 is a protein which in humans is encoded by the CCL5 gene. The gene has been discovered in 1990 by in situ hybridisation and it is localised on 17q11.2-q12 chromosome. It is also known as RANTES. RANTES was first described by Dr. Tom Schall who named the protein, the original source of the name Rantes was from the Argentine movie Man Facing Southeast about an alien who shows up in a mental ward who was named Rantés, the rather clunky acronym was only made to fit the name.

<span class="mw-page-title-main">Macrophage inflammatory protein</span> Protein family

Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1α and MIP-1β that are now officially named CCL3 and CCL4, respectively. However, other names can sometimes be encountered, especially in older literature, as LD78α, AT 464.1 and GOS19-1 for human CCL3 and AT 744, Act-2, LAG-1, HC21 and G-26 for human CCL4. Other macrophage inflammatory proteins include MIP-2, MIP-3 and MIP-5.

<span class="mw-page-title-main">CCL28</span> Mammalian protein found in Homo sapiens

Chemokine ligand 28 (CCL28), also known as mucosae-associated epithelial chemokine (MEC), CCK1 and SCYA28, is a chemokine. CCL28 regulates the chemotaxis of cells that express the chemokine receptors CCR3 and CCR10. CCL28 is expressed by columnar epithelial cells in the gut, lung, breast and the salivary glands and drives the mucosal homing of T and B lymphocytes that express CCR10, and the migration of eosinophils expressing CCR3. This chemokine is constitutively expressed in the colon, but its levels can be increased by pro-inflammatory cytokines and certain bacterial products implying a role in effector cell recruitment to sites of epithelial injury. CCL28 has also been implicated in the migration of IgA-expressing cells to the mammary gland, salivary gland, intestine and other mucosal tissues. It has also been shown as a potential antimicrobial agent effective against certain pathogens, such as Gram negative and Gram positive bacteria and the fungus Candida albicans.

<span class="mw-page-title-main">CCL7</span> Mammalian protein found in Homo sapiens

Chemokine ligand 7 (CCL7) is a small cytokine that was previously called monocyte-chemotactic protein 3 (MCP3). CCL7 is a small protein that belongs to the CC chemokine family and is most closely related to CCL2.

<span class="mw-page-title-main">CCL11</span> Mammalian protein found in Homo sapiens

C-C motif chemokine 11 also known as eosinophil chemotactic protein and eotaxin-1 is a protein that in humans is encoded by the CCL11 gene. This gene is encoded on three exons and is located on chromosome 17.

<span class="mw-page-title-main">CCL20</span> Mammalian protein found in Homo sapiens

Chemokine ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly attracts neutrophils. CCL20 is implicated in the formation and function of mucosal lymphoid tissues via chemoattraction of lymphocytes and dendritic cells towards the epithelial cells surrounding these tissues. CCL20 elicits its effects on its target cells by binding and activating the chemokine receptor CCR6.

Chemokine ligand 16 (CCL16) is a small cytokine belonging to the CC chemokine family that is known under several pseudonyms, including Liver-expressed chemokine (LEC) and Monotactin-1 (MTN-1). This chemokine is expressed by the liver, thymus, and spleen and is chemoattractive for monocytes and lymphocytes. Cellular expression of CCL16 can be strongly induced in monocytes by IL-10, IFN-γ and bacterial lipopolysaccharide. Its gene is located on chromosome 17, in humans, among a cluster of other CC chemokines. CCL16 elicits its effects on cells by interacting with cell surface chemokine receptors such as CCR1, CCR2, CCR5 and CCR8.

<span class="mw-page-title-main">CCL21</span> Mammalian protein found in Homo sapiens

Chemokine ligand 21 (CCL21) is a small cytokine belonging to the CC chemokine family. This chemokine is also known as 6Ckine, exodus-2, and secondary lymphoid-tissue chemokine (SLC). CCL21 elicits its effects by binding to a cell surface chemokine receptor known as CCR7. The main function of CCL21 is to guide CCR7 expressing leukocytes to the secondary lymphoid organs, such as lymph nodes and Peyer´s patches.

<span class="mw-page-title-main">CCL17</span> Mammalian protein found in Homo sapiens

CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an immune response. However, in other cancers, such as melanoma, an increase in CCL17 is linked to an improved outcome. CCL17 has also been linked to autoimmune and allergic diseases.

<span class="mw-page-title-main">CCL19</span> Mammalian protein found in Homo sapiens

Chemokine ligand 19 (CCL19) is a protein that in humans is encoded by the CCL19 gene.

<span class="mw-page-title-main">CXCL9</span> Mammalian protein found in Homo sapiens

Chemokine ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as monokine induced by gamma interferon (MIG). The CXCL9 is one of the chemokine which plays role to induce chemotaxis, promote differentiation and multiplication of leukocytes, and cause tissue extravasation.

<span class="mw-page-title-main">C-C chemokine receptor type 7</span> Protein-coding gene in the species Homo sapiens

C-C chemokine receptor type 7 is a protein that in humans is encoded by the CCR7 gene. Two ligands have been identified for this receptor: the chemokines ligand 19 (CCL19/ELC) and ligand 21 (CCL21). The ligands have similar affinity for the receptor, though CCL19 has been shown to induce internalisation of CCR7 and desensitisation of the cell to CCL19/CCL21 signals. CCR7 is a transmembrane protein with 7 transmembrane domains, which is coupled with heterotrimeric G proteins, which transduce the signal downstream through various signalling cascades. The main function of the receptor is to guide immune cells to immune organs by detecting specific chemokines, which these tissues secrete.

<span class="mw-page-title-main">CCR1</span> Protein in humans

C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.

<span class="mw-page-title-main">C-C chemokine receptor type 6</span> Mammalian protein found in Homo sapiens

Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene. CCR6 has also recently been designated CD196. The gene is located on the long arm of Chromosome 6 (6q27) on the Watson (plus) strand. It is 139,737 bases long and encodes a protein of 374 amino acids.

<span class="mw-page-title-main">CCR10</span> Protein-coding gene in the species Homo sapiens

C-C chemokine receptor type 10 is a protein that in humans is encoded by the CCR10 gene.

<span class="mw-page-title-main">CCR3 (gene)</span> Mammalian protein found in Homo sapiens

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

<span class="mw-page-title-main">CCBP2</span> Protein-coding gene in the species Homo sapiens

Chemokine-binding protein 2 is a protein that in humans is encoded by the CCBP2 gene.

<span class="mw-page-title-main">CCL3L1</span> Protein-coding gene in the species Homo sapiens

Chemokine ligand 3-like 1, also known as CCL3L1, is a protein which in humans is encoded by the CCL3L1 gene.

<span class="mw-page-title-main">C-C motif chemokine ligand 27</span> Mammalian protein found in Homo sapiens

C-C motif chemokine ligand 27 is a protein that in humans is encoded by the CCL27 gene.

References

  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. 1 2 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. 1 2 3 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. 1 2 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. 1 2 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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