7tuy

Structural highlights

Function

[GP183_HUMAN] G-protein coupled receptor expressed in lymphocytes that acts as a chemotactic receptor for B-cells, T-cells, splenic dendritic cells, monocytes/macrophages and astrocytes (By similarity). Receptor for oxysterol 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) and other related oxysterols (PubMed:21796212, PubMed:22875855, PubMed:22930711). Mediates cell positioning and movement of a number of cells by binding the 7-alpha,25-OHC ligand that forms a chemotactic gradient (By similarity). Binding of 7-alpha,25-OHC mediates the correct localization of B-cells during humoral immune responses (By similarity). Guides B-cell movement along the B-cell zone-T-cell zone boundary and later to interfollicular and outer follicular regions (By similarity). Its specific expression during B-cell maturation helps position B-cells appropriately for mounting T-dependent antibody responses (By similarity). Collaborates with CXCR5 to mediate B-cell migration; probably by forming a heterodimer with CXCR5 that affects the interaction between of CXCL13 and CXCR5 (PubMed:22913878). Also acts as a chemotactic receptor for some T-cells upon binding to 7-alpha,25-OHC ligand (By similarity). Promotes follicular helper T (Tfh) cells differentiation by positioning activated T-cells at the follicle-T-zone interface, promoting contact of newly activated CD4 T-cells with activated dendritic cells and exposing them to Tfh-cell-promoting inducible costimulator (ICOS) ligand (By similarity). Expression in splenic dendritic cells is required for their homeostasis, localization and ability to induce B- and T-cell responses: GPR183 acts as a chemotactic receptor in dendritic cells that mediates the accumulation of CD4(+) dendritic cells in bridging channels (By similarity). Regulates migration of astrocytes and is involved in communication between astrocytes and macrophages (PubMed:25297897). Promotes osteoclast precursor migration to bone surfaces (By similarity). Signals constitutively through G(i)-alpha, but not G(s)-alpha or G(q)-alpha (PubMed:21673108, PubMed:25297897). Signals constitutively also via MAPK1/3 (ERK1/2) (By similarity).[UniProtKB:Q3U6B2]^{[1] [2] [3] [4] [5] [6] [7]}

References

1. ↑ Rosenkilde MM, Benned-Jensen T, Andersen H, Holst PJ, Kledal TN, Luttichau HR, Larsen JK, Christensen JP, Schwartz TW. Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity. J Biol Chem. 2006 May 12;281(19):13199-13208. doi: 10.1074/jbc.M602245200. Epub, 2006 Mar 15. PMID:16540462 doi:http://dx.doi.org/10.1074/jbc.M602245200
2. ↑ Benned-Jensen T, Smethurst C, Holst PJ, Page KR, Sauls H, Sivertsen B, Schwartz TW, Blanchard A, Jepras R, Rosenkilde MM. Ligand modulation of the Epstein-Barr virus-induced seven-transmembrane receptor EBI2: identification of a potent and efficacious inverse agonist. J Biol Chem. 2011 Aug 19;286(33):29292-29302. doi: 10.1074/jbc.M110.196345. Epub , 2011 Jun 14. PMID:21673108 doi:http://dx.doi.org/10.1074/jbc.M110.196345
3. ↑ Hannedouche S, Zhang J, Yi T, Shen W, Nguyen D, Pereira JP, Guerini D, Baumgarten BU, Roggo S, Wen B, Knochenmuss R, Noel S, Gessier F, Kelly LM, Vanek M, Laurent S, Preuss I, Miault C, Christen I, Karuna R, Li W, Koo DI, Suply T, Schmedt C, Peters EC, Falchetto R, Katopodis A, Spanka C, Roy MO, Detheux M, Chen YA, Schultz PG, Cho CY, Seuwen K, Cyster JG, Sailer AW. Oxysterols direct immune cell migration via EBI2. Nature. 2011 Jul 27;475(7357):524-7. doi: 10.1038/nature10280. PMID:21796212 doi:http://dx.doi.org/10.1038/nature10280
4. ↑ Benned-Jensen T, Norn C, Laurent S, Madsen CM, Larsen HM, Arfelt KN, Wolf RM, Frimurer T, Sailer AW, Rosenkilde MM. Molecular characterization of oxysterol binding to the Epstein-Barr virus-induced gene 2 (GPR183). J Biol Chem. 2012 Oct 12;287(42):35470-35483. doi: 10.1074/jbc.M112.387894. Epub , 2012 Aug 8. PMID:22875855 doi:http://dx.doi.org/10.1074/jbc.M112.387894
5. ↑ Barroso R, Martinez Munoz L, Barrondo S, Vega B, Holgado BL, Lucas P, Baillo A, Salles J, Rodriguez-Frade JM, Mellado M. EBI2 regulates CXCL13-mediated responses by heterodimerization with CXCR5. FASEB J. 2012 Dec;26(12):4841-54. doi: 10.1096/fj.12-208876. Epub 2012 Aug 22. PMID:22913878 doi:http://dx.doi.org/10.1096/fj.12-208876
6. ↑ Zhang L, Shih AY, Yang XV, Kuei C, Wu J, Deng X, Mani NS, Mirzadegan T, Sun S, Lovenberg TW, Liu C. Identification of structural motifs critical for epstein-barr virus-induced molecule 2 function and homology modeling of the ligand docking site. Mol Pharmacol. 2012 Dec;82(6):1094-103. doi: 10.1124/mol.112.080275. Epub 2012, Aug 28. PMID:22930711 doi:http://dx.doi.org/10.1124/mol.112.080275
7. ↑ Rutkowska A, Preuss I, Gessier F, Sailer AW, Dev KK. EBI2 regulates intracellular signaling and migration in human astrocyte. Glia. 2015 Feb;63(2):341-51. doi: 10.1002/glia.22757. Epub 2014 Oct 9. PMID:25297897 doi:http://dx.doi.org/10.1002/glia.22757