Biology:CC chemokine receptors
| CCR1 | |
|---|---|
| Identifiers | |
| Symbol | CCR1 |
| NCBI gene | 1230 |
| HGNC | 1602 |
| OMIM | 601159 |
| RefSeq | NM_001295 |
| UniProt | P32246 |
| Other data | |
| Locus | Chr. 3 p21 |
| CCR2 | |
|---|---|
| Identifiers | |
| Symbol | CCR2 |
| NCBI gene | 1231 |
| HGNC | 1603 |
| OMIM | 601268 |
| PDB | 1KAD |
| RefSeq | NM_000647 |
| UniProt | P41597 |
| Other data | |
| Locus | Chr. 3 p21 |
| CCR3 | |
|---|---|
| Identifiers | |
| Symbol | CCR3 |
| NCBI gene | 1232 |
| HGNC | 1604 |
| OMIM | 601268 |
| RefSeq | NM_001837 |
| UniProt | P51677 |
| Other data | |
| Locus | Chr. 3 p21 |
| CCR4 | |
|---|---|
| Identifiers | |
| Symbol | CCR4 |
| NCBI gene | 1233 |
| HGNC | 1605 |
| OMIM | 604836 |
| RefSeq | NM_005508 |
| UniProt | P51679 |
| Other data | |
| Locus | Chr. 3 p24 |
| CCR5 | |
|---|---|
| Identifiers | |
| Symbol | CCR5 |
| NCBI gene | 1234 |
| HGNC | 1606 |
| OMIM | 601373 |
| PDB | 1ND8 |
| RefSeq | NM_000579 |
| UniProt | P51681 |
| Other data | |
| Locus | Chr. 3 p21 |
| CCR6 | |
|---|---|
| Identifiers | |
| Symbol | CCR6 |
| NCBI gene | 1235 |
| HGNC | 1607 |
| OMIM | 601835 |
| RefSeq | NM_004367 |
| UniProt | P51684 |
| Other data | |
| Locus | Chr. 6 q27 |
| CCR7 | |
|---|---|
| Identifiers | |
| Symbol | CCR7 |
| NCBI gene | 1236 |
| HGNC | 1608 |
| OMIM | 600242 |
| RefSeq | NM_001838 |
| UniProt | P32248 |
| Other data | |
| Locus | Chr. 17 q12-q21.2 |
| CCR8 | |
|---|---|
| Identifiers | |
| Symbol | CCR8 |
| NCBI gene | 1237 |
| HGNC | 1609 |
| OMIM | 601834 |
| RefSeq | NM_005201 |
| UniProt | P51685 |
| Other data | |
| Locus | Chr. 3 p22 |
| CCR9 | |
|---|---|
| Identifiers | |
| Symbol | CCR9 |
| NCBI gene | 10803 |
| HGNC | 1610 |
| OMIM | 604738 |
| RefSeq | NM_031200 |
| UniProt | P51686 |
| Other data | |
| Locus | Chr. 3 p21 |
| CCR10 | |
|---|---|
| Identifiers | |
| Symbol | CCR10 |
| NCBI gene | 2826 |
| HGNC | 4474 |
| OMIM | 600240 |
| RefSeq | NM_016602 |
| UniProt | P46092 |
| Other data | |
| Locus | Chr. 17 17q21.1-q21 |
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.
Mechanism
The CC chemokine receptors all work by activating the G protein Gi.[1]
Types
Overview table
| 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
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.
References
- ↑ senselab
- ↑ "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. February 2004. doi:10.4049/jimmunol.172.3.1872. PMID 14734772.
- ↑ 3.0 3.1 "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. December 1997. doi:10.4049/jimmunol.159.11.5201. PMID 9548457.
- ↑ 4.0 4.1 4.2 "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. August 2001. doi:10.1093/intimm/13.8.1021. PMID 11470772.
- ↑ 5.0 5.1 "Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5". Blood 97 (7): 1920–4. April 2001. doi:10.1182/blood.v97.7.1920. PMID 11264152.
- ↑ "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. September 1999. doi:10.1074/jbc.274.39.27975. PMID 10488147.
- ↑ "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. March 1996. doi:10.1074/jbc.271.13.7725. PMID 8631813.
- ↑ 8.0 8.1 "A novel chemokine ligand for CCR10 and CCR3 expressed by epithelial cells in mucosal tissues". Journal of Immunology 165 (6): 2943–9. September 2000. doi:10.4049/jimmunol.165.6.2943. PMID 10975800.
- ↑ "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. November 1997. doi:10.1002/jlb.62.5.667. PMID 9365122.
- ↑ "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. June 1997. doi:10.1074/jbc.272.23.15036. PMID 9169480.
- ↑ "Macrophage-derived chemokine is a functional ligand for the CC chemokine receptor 4". The Journal of Biological Chemistry 273 (3): 1764–8. January 1998. doi:10.1074/jbc.273.3.1764. PMID 9430724.
- ↑ "Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication". The Journal of Biological Chemistry 273 (8): 4289–92. February 1998. doi:10.1074/jbc.273.8.4289. PMID 9468473.
- ↑ "CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist". Blood 94 (6): 1899–905. September 1999. doi:10.1182/blood.V94.6.1899. PMID 10477718.
- ↑ "Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells". Nature Immunology 8 (6): 639–46. June 2007. doi:10.1038/ni1467. PMID 17486092.
- ↑ "Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC". The Journal of Biological Chemistry 272 (23): 14893–8. June 1997. doi:10.1074/jbc.272.23.14893. PMID 9169459.
- ↑ "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. May 1997. doi:10.1074/jbc.272.21.13803. PMID 9153236.
- ↑ "Identification of CCR8, the receptor for the human CC chemokine I-309". The Journal of Biological Chemistry 272 (28): 17251–4. July 1997. doi:10.1074/jbc.272.28.17251. PMID 9211859.
- ↑ "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. May 1999. doi:10.4049/jimmunol.162.10.5671. PMID 10229797.
- ↑ "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. March 2000. doi:10.4049/jimmunol.164.6.2851. PMID 10706668.
- ↑ "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. April 2000. doi:10.4049/jimmunol.164.7.3465. PMID 10725697.
- ↑ "Identification of a novel chemokine (CCL28), which binds CCR10 (GPR2)". The Journal of Biological Chemistry 275 (29): 22313–23. July 2000. doi:10.1074/jbc.M001461200. PMID 10781587.
External links
- "Chemokine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1280.
 |  |
