Alternative titles; symbols
HGNC Approved Gene Symbol: CD200R1
Cytogenetic location: 3q13.2 Genomic coordinates (GRCh38) : 3:112,921,205-112,975,103 (from NCBI)
CD200R, or OX2R, is a myeloid cell-specific surface glycoprotein that interacts with OX2 (MOX2; 155970).
Using immunoprecipitation of rat splenic lysates, followed by 5-prime and 3-prime RACE and PCR, Wright et al. (2000) obtained cDNAs encoding mouse and rat Ox2r. Like Ox2, Ox2r contains 2 immunoglobulin (Ig) superfamily domains (V and C2 sets) and a single transmembrane region. However, the 67-amino acid cytoplasmic domain of Ox2r is larger than that of Ox2, and it contains 3 conserved tyrosine residues, 1 of which is within an NPXY motif. NPXY motifs bind the PTB/PID domains present in signaling adaptor molecules such as SHC (600560), IRS1 (147545), and NUMB (603728), suggesting that Ox2r engagement by Ox2 may lead to intracellular signals affecting macrophage function. The rodent Ox2r proteins have at least 8 potential N-linked glycosylation sites. Pervanadate treatment indicated that Ox2r can be phosphorylated on tyrosine residues. Flow cytometric analysis demonstrated Ox2r expression on rat macrophages and dendritic cells, but not on lymphocytes.
By searching EST databases for homologs of rat Cd200r, followed by PCR of a lung cDNA library, Wright et al. (2003) cloned human CD200R. The deduced 325-amino acid type I cell surface glycoprotein contains a leader peptide, 2 Ig-like domains in the V/C2 arrangement, a hydrophobic transmembrane sequence, and a substantial cytoplasmic region. All extracellular cysteines, 8 N-glycosylation sites, and 3 tyrosine phosphorylation sites are conserved with rat Cd200r. Wright et al. (2003) also cloned a CD200R splice variant that encodes a protein with 23 additional amino acids in the N-terminal leader peptide. RT-PCR analysis detected strongest CD200R expression in bone marrow, followed by lymph node, spleen, and lung. In cell lines, highest expression was in dendritic cells, followed by Th2 cells and mast cells. Flow cytometric analysis revealed highest expression in peripheral blood T cells, neutrophils, and basophils, with moderate levels in monocytes and low levels in natural killer and B cells.
Functional analysis by Wright et al. (2000) showed that rat Ox2r expressed in a human kidney epithelium cell line bound Ox2. Using the experimental allergic encephalitis (EAE) model in rats, they showed that blocking the Ox2-Ox2r interaction augmented the severity but not the duration of EAE disease.
Dick et al. (2001) used FACS and immunohistochemical analyses to show that Ox2 was expressed in normal rat myeloid-derived retinal cells, while both Ox2 and Ox2r were expressed in inflamed retinal tissue during experimental autoimmune uveoretinitis.
Using biacore analysis, Wright et al. (2003) showed that human CD200R interacts with CD200.
By flow cytometry and immunohistochemical analysis, Cherwinski et al. (2005) found that CD200R was expressed on human and murine mast cells. Engagement of CD200R by CD200 resulted in potent inhibition of mast cell degranulation and cytokine secretion. Cherwinski et al. (2005) noted that CD200R does not contain an immunoreceptor tyrosine-based inhibitory motif (ITIM) and thus represents a novel receptor that can be targeted in vivo to regulate mast cell-dependent pathologies.
By genomic sequence analysis, Wright et al. (2003) mapped CD200, CD200R, and a closely related gene, CD200RL, to chromosome 3. The CD200RL gene appeared to be nonfunctional in humans.
Cherwinski, H. M., Murphy, C. A., Joyce, B. L., Bigler, M. E., Song, Y. S., Zurawski, S. M., Moshrefi, M. M., Gorman, D. M., Miller, K. L., Zhang, S., Sedgwick, J. D., Phillips, J. H. The CD200 receptor is a novel and potent regulator of murine and human mast cell function. J. Immun. 174: 1348-1356, 2005. [PubMed: 15661892] [Full Text: https://doi.org/10.4049/jimmunol.174.3.1348]
Dick, A. D., Broderick, C., Forrester, J. V., Wright, G. J. Distribution of OX2 antigen and OX2 receptor within retina. Invest. Ophthal. Vis. Sci. 42: 170-176, 2001. [PubMed: 11133863]
Wright, G. J., Cherwinski, H., Foster-Cuevas, M., Brooke, G., Puklavec, M. J., Bigler, M., Song, Y., Jenmalm, M., Gorman, D., McClanahan, T., Liu, M.-R., Brown, M. H., Sedgwick, J. D., Phillips, J. H., Barclay, A. N. Characterization of the CD200 receptor family in mice and humans and their interactions with CD200. J. Immun. 171: 3034-3046, 2003. [PubMed: 12960329] [Full Text: https://doi.org/10.4049/jimmunol.171.6.3034]
Wright, G. J., Puklavec, M. J., Willis, A. C., Hoek, R. M., Sedgwick, J. D., Brown, M. H., Barclay, A. N. Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Immunity 13: 233-242, 2000. [PubMed: 10981966] [Full Text: https://doi.org/10.1016/s1074-7613(00)00023-6]