Fc receptor-like 3 (FCRL3)

Fc receptor-like 3 (FCRL3), also known as CD307c or MAIA, is a type I transmembrane glycoprotein belonging to the Fc receptor-like family and the immunoglobulin superfamily. It is primarily expressed on the surface of B cells, natural killer (NK) cells, and specific T cell subsets, most notably regulatory T cells (Tregs). FCRL3 is unique among its family members for possessing both immunoreceptor tyrosine-based activation motifs (ITAMs) and inhibitory motifs (ITIMs) in its cytoplasmic tail, enabling it to act as a complex bidirectional regulator of immune signaling. Recent research has identified FCRL3 as a receptor for secretory IgA (sIgA) and as a critical factor in sperm-egg fusion, where it interacts with JUNO and IZUMO1. Genetic polymorphisms in the FCRL3 promoter, such as the rs7528684 (-169C/T) variant, are strongly linked to an increased risk of various autoimmune disorders, including rheumatoid arthritis and systemic lupus erythematosus, by modulating its expression levels. While no therapeutic agents targeting FCRL3 are currently approved, it is being actively investigated as a potential drug target and biomarker for autoimmune diseases and certain T-cell malignancies like Sezary syndrome.

Other names

CD307cFCRH3IRTA3IFGP3SPAP2MAIAFc receptor homolog 3Immune receptor translocation-associated protein 3SH2 domain-containing phosphatase anchor protein 2

Modulates B-cell and T-cell receptor signaling via cytoplasmic ITAM and ITIM motifs; recruits phosphatases such as SHP-1 and SHP-2 to inhibit activation; acts as a receptor for secretory IgA to suppress Treg function.