C-C chemokine receptor type 6

Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene.[5] CCR6 has also recently been designated CD196 (cluster of differentiation 196). 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 (molecular weight 42,494 Da).[5]

CCR6
Identifiers
Aliases	CCR6, BN-1, C-C CKR-6, CC-CKR-6, CCR-6, CD196, CKR-L3, CKRL3, CMKBR6, DCR2, DRY6, GPR29, GPRCY4, STRL22, C-C motif chemokine receptor 6
External IDs	OMIM: 601835 MGI: 1333797 HomoloGene: 3214 GeneCards: CCR6
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q27 Start 167,111,807 bp[1] End 167,139,696 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 A1 Start 8,236,043 bp[2] End 8,257,141 bp[2]
Gene ontology Molecular function • G-protein coupled receptor activity • signal transducer activity • chemokine receptor activity • GO:0001948 protein binding • C-C chemokine receptor activity • C-C chemokine binding • signaling receptor activity • chemokine binding Cellular component • integral component of membrane • membrane • cell membrane • integral component of plasma membrane • intracellular • cell surface • sperm midpiece • sperm flagellum • sperm principal piece • sperm plasma membrane • external side of plasma membrane Biological process • positive regulation of cytosolic calcium ion concentration • positive regulation of epithelial cell migration • dendritic cell chemotaxis • cellular defense response • humoral immune response • immune response • positive regulation of dendritic cell chemotaxis • signal transduction • calcium-mediated signaling • chemotaxis • cell chemotaxis • chemokine-mediated signaling pathway • leukocyte migration involved in inflammatory response • isotype switching to IgA isotypes • positive regulation of flagellated sperm motility involved in capacitation • lymphocyte migration • T cell migration • thymocyte migration • DN2 thymocyte differentiation • DN3 thymocyte differentiation • regulation of T cell migration • G-protein coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1235	12458
Ensembl	ENSG00000112486	ENSMUSG00000040899
UniProt	P51684	O54689
RefSeq (mRNA)	NM_031409 NM_004367	NM_001190333 NM_001190334 NM_001190335 NM_001190336 NM_001190337 NM_001190338 NM_009835
RefSeq (protein)	NP_004358 NP_113597	NP_001177262 NP_001177263 NP_001177264 NP_001177265 NP_001177266 NP_001177267 NP_033965
Location (UCSC)	Chr 6: 167.11 – 167.14 Mb	Chr 17: 8.24 – 8.26 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This protein belongs to family A of G protein-coupled receptor superfamily. The gene is expressed in lymphatic and non-lymphatic tissue as spleen, lymph nodes, pancreas, colon, appendix, small intestine. CCR6 is expressed on B-cells, immature dendritic cells (DC), T-cells (Th1, Th2, Th17, Treg), natural killer cells (NKT cells) and neutrophils.[6] The ligand of this receptor is CCL20 or in the other name - macrophage inflammatory protein 3 alpha (MIP-3 alpha). This chemokine receptor is special because it bind only one chemokine ligand CCL20 in compare to other chemokine receptors.[7] CCR6 has a key role in connection between immature DC an adaptive immunity.[8] This receptor has been shown to be important for B-lineage maturation and antigen-driven B-cell differentiation, and it may regulate the migration and recruitment of dendritic cells and T cells during inflammatory and immunological responses. Alternatively spliced transcript variants that encode the same protein have been described for this gene.[9]

Interleukin 4 (IL-4) and interferon gamma (IFNγ) suppress expression of CCR6 in langerhans cells development and interleukin 10 (IL-10) induces the expression. It can regulate immune response in inflammatory tissue.[10]

Proinflammatory Th17 cells express CCR6 and its ligand CCL20. CCR6 influences their migration to sites of inflammation. Some Th17 cells migrate via chemokine gradient of CCL20 to inflammatory sites and themselves can express more CCL20 to bring in more Th17 cells and regulatory T-cells (Treg). This can lead to chronic inflammation. In some models, the lack of CCR6 leads to less severe autoimmune encephalomyelitis.[11]

Clinical significance

CCR6 has a function in development and metastatic spread of gastrointestinal malignancies.[7] Expression of CCR6 was found to be up-regulated in colorectal cancer.[12] Many patients with colorectal cancer have liver metastases. Colorectal carcinoma cells express CCR6 and CCL20. High level of CCL20 in liver chemoattract colorectal carcinoma cells and cause metastases in liver.[7][13] Novel research has identified a microRNA that is able to downregulate CCR6 in cancer cell lines.[14]

CCR6 has been associated with Crohn's disease.[15]

References

1. GRCh38: Ensembl release 89: ENSG00000112486 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040899 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Zaballos A, Varona R, Gutiérrez J, Lind P, Márquez G (October 1996). "Molecular cloning and RNA expression of two new human chemokine receptor-like genes". Biochem. Biophys. Res. Commun. 227 (3): 846–53. doi:10.1006/bbrc.1996.1595. PMID 8886020.
6. Schutyser, Evemie; Struyf, Sofie; Van Damme, Jo (October 2003). "The CC chemokine CCL20 and its receptor CCR6". Cytokine & Growth Factor Reviews. 14 (5): 409–426. doi:10.1016/s1359-6101(03)00049-2. ISSN 1359-6101. PMID 12948524.
7. Frick, Vilma Oliveira; Rubie, Claudia; Keilholz, Ulrich; Ghadjar, Pirus (2016-01-14). "Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview". World Journal of Gastroenterology. 22 (2): 833–841. doi:10.3748/wjg.v22.i2.833. ISSN 2219-2840. PMC 4716081. PMID 26811629.
8. Dieu, M. C.; Vanbervliet, B.; Vicari, A.; Bridon, J. M.; Oldham, E.; Aït-Yahia, S.; Brière, F.; Zlotnik, A.; Lebecque, S.; Caux, C. (1998-07-20). "Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites". The Journal of Experimental Medicine. 188 (2): 373–386. doi:10.1084/jem.188.2.373. ISSN 0022-1007. PMC 2212459. PMID 9670049.
9. "Entrez Gene: CCR6 chemokine (C-C motif) receptor 6".
10. Dieu-Nosjean, Marie-Caroline; Massacrier, Catherine; Vanbervliet, Béatrice; Fridman, Wolf-Herman; Caux, Christophe (2001-11-15). "IL-10 Induces CCR6 Expression During Langerhans Cell Development While IL-4 and IFN-γ Suppress It". The Journal of Immunology. 167 (10): 5594–5602. doi:10.4049/jimmunol.167.10.5594. ISSN 0022-1767. PMID 11698430.
11. Yamazaki, Tomohide; Yang, Xuexian O.; Chung, Yeonseok; Fukunaga, Atsushi; Nurieva, Roza; Pappu, Bhanu; Martin-Orozco, Natalia; Kang, Hong Soon; Ma, Li; Panopoulos, Athanasia D.; Craig, Suzanne (2008-12-15). "CCR6 Regulates the Migration of Inflammatory and Regulatory T Cells". The Journal of Immunology. 181 (12): 8391–8401. doi:10.4049/jimmunol.181.12.8391. ISSN 0022-1767. PMC 2752441. PMID 19050256.
12. Rubie, Claudia; Kruse, Bianca; Frick, Vilma Oliveira; Kölsch, Kathrin; Ghadjar, Pirus; Wagner, Mathias; Grässer, Friedrich; Wagenpfeil, Stefan; Glanemann, Mathias (2014-02-21). "Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells". Journal of Translational Medicine. 12: 48. doi:10.1186/1479-5876-12-48. ISSN 1479-5876. PMC 3996063. PMID 24559209.
13. Frick, V. O.; .Rubie, C.; Kölsch, K.; Wagner, M.; Ghadjar, P.; Graeber, S.; Glanemann, M. (September 2013). "CCR6/CCL20 Chemokine Expression Profile in Distinct Colorectal Malignancies". Scandinavian Journal of Immunology. 78 (3): 298–305. doi:10.1111/sji.12087. PMID 23790181.
14. Rubie C (Feb 2014). "Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells". J Transl Med. 12: 48. doi:10.1186/1479-5876-12-48. PMC 3996063. PMID 24559209.
15. Wang K, Zhang H, Kugathasan S, Annese V, Bradfield JP, Russell RK, Sleiman PM, Imielinski M, Glessner J, Hou C, Wilson DC, Walters T, Kim C, Frackelton EC, Lionetti P, Barabino A, Van Limbergen J, Guthery S, Denson L, Piccoli D, Li M, Dubinsky M, Silverberg M, Griffiths A, Grant SF, Satsangi J, Baldassano R, Hakonarson H (February 2009). "Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease". Am. J. Hum. Genet. 84 (3): 399–405. doi:10.1016/j.ajhg.2009.01.026. PMC 2668006. PMID 19249008.

External links

• Human CCR6 genome location and CCR6 gene details page in the UCSC Genome Browser.
• "Chemokine Receptors: CCR6". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Zaballos A, Varona R, Gutiérrez J, et al. (1996). "Molecular cloning and RNA expression of two new human chemokine receptor-like genes". Biochem. Biophys. Res. Commun. 227 (3): 846–53. doi:10.1006/bbrc.1996.1595. PMID 8886020.
• Liao F, Lee HH, Farber JM (1997). "Cloning of STRL22, a new human gene encoding a G-protein-coupled receptor related to chemokine receptors and located on chromosome 6q27". Genomics. 40 (1): 175–80. doi:10.1006/geno.1996.4544. PMID 9070937.
• Baba M, Imai T, Nishimura M, et al. (1997). "Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC". J. Biol. Chem. 272 (23): 14893–8. doi:10.1074/jbc.272.23.14893. PMID 9169459.
• Wagner T, Tommerup N, Wirth J, et al. (1997). "A somatic cell hybrid panel for distal 17q: GDIA1 maps to 17q25.3". Cytogenet. Cell Genet. 76 (3–4): 172–5. doi:10.1159/000134538. PMID 9186513.
• Liao F, Alderson R, Su J, et al. (1997). "STRL22 is a receptor for the CC chemokine MIP-3alpha". Biochem. Biophys. Res. Commun. 236 (1): 212–7. doi:10.1006/bbrc.1997.6936. PMID 9223454.
• Power CA, Church DJ, Meyer A, et al. (1997). "Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells". J. Exp. Med. 186 (6): 825–35. doi:10.1084/jem.186.6.825. PMC 2199050. PMID 9294137.
• Greaves DR, Wang W, Dairaghi DJ, et al. (1997). "CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3alpha and is highly expressed in human dendritic cells". J. Exp. Med. 186 (6): 837–44. doi:10.1084/jem.186.6.837. PMC 2199049. PMID 9294138.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Yang D, Chertov O, Bykovskaia SN, et al. (1999). "Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6". Science. 286 (5439): 525–8. doi:10.1126/science.286.5439.525. PMID 10521347.
• Krzysiek R, Lefevre EA, Bernard J, et al. (2000). "Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha/CCL20 in human B cells". Blood. 96 (7): 2338–45. doi:10.1182/blood.V96.7.2338. PMID 11001880.
• Douglas GC, Thirkill TL, Sideris V, et al. (2001). "Chemokine receptor expression by human syncytiotrophoblast". J. Reprod. Immunol. 49 (2): 97–114. doi:10.1016/S0165-0378(00)00083-8. PMID 11164896.
• Biragyn A, Surenhu M, Yang D, et al. (2002). "Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens". J. Immunol. 167 (11): 6644–53. doi:10.4049/jimmunol.167.11.6644. PMID 11714836.
• Ebert LM, McColl SR (2002). "Up-regulation of CCR5 and CCR6 on distinct subpopulations of antigen-activated CD4+ T lymphocytes". J. Immunol. 168 (1): 65–72. doi:10.4049/jimmunol.168.1.65. PMID 11751947.
• Liao F, Shirakawa AK, Foley JF, et al. (2002). "Human B cells become highly responsive to macrophage-inflammatory protein-3 alpha/CC chemokine ligand-20 after cellular activation without changes in CCR6 expression or ligand binding". J. Immunol. 168 (10): 4871–80. doi:10.4049/jimmunol.168.10.4871. PMID 11994436.
• Hosokawa Y, Nakanishi T, Yamaguchi D, et al. (2002). "Macrophage inflammatory protein 3alpha-CC chemokine receptor 6 interactions play an important role in CD4+ T-cell accumulation in periodontal diseased tissue". Clin. Exp. Immunol. 128 (3): 548–54. doi:10.1046/j.1365-2249.2002.01865.x. PMC 1906256. PMID 12067311.
• Kim CH, Johnston B, Butcher EC (2002). "Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among V alpha 24(+)V beta 11(+) NKT cell subsets with distinct cytokine-producing capacity". Blood. 100 (1): 11–6. doi:10.1182/blood-2001-12-0196. PMID 12070001.
• Ai LS, Liao F (2002). "Mutating the four extracellular cysteines in the chemokine receptor CCR6 reveals their differing roles in receptor trafficking, ligand binding, and signaling". Biochemistry. 41 (26): 8332–41. doi:10.1021/bi025855y. PMID 12081481.
• Hoover DM, Boulegue C, Yang D, et al. (2002). "The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins". J. Biol. Chem. 277 (40): 37647–54. doi:10.1074/jbc.M203907200. PMID 12149255.
• Maki W, Morales RE, Carroll VA, et al. (2002). "CCR6 colocalizes with CD18 and enhances adhesion to activated endothelial cells in CCR6-transduced Jurkat T cells". J. Immunol. 169 (5): 2346–53. doi:10.4049/jimmunol.169.5.2346. PMID 12193700.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.