CD200R2

CD200R2 (CD200R1L, CD200 receptor-like 2) is a member of the CD200 receptor gene cluster, arising from duplication of an ancestral CD200R gene on human chromosome 1 and mouse chromosome 16. CD200R2 is a type I transmembrane protein of the Ig superfamily whose extracellular region comprises one V-set and one C2-set Ig domain; unlike canonical CD200R1, human CD200R2 is considered a pseudogene in many individuals or exhibits limited expression, while murine CD200R2 is a functional receptor expressed on myeloid cells, particularly resident macrophage populations including microglia, Langerhans cells and peritoneal macrophages. Murine CD200R2 does not bind CD200; instead, it associates with CD200R3 and other family members to form functional receptor complexes, and can pair with DAP12 to transmit activating signals in basophils and mast cells, participating in IgE-mediated allergic responses. This dual activating capacity distinguishes CD200R2 from the purely inhibitory CD200R1 and suggests a regulatory diversification of the CD200 receptor family during evolution of innate immune cell specialization.