FCRL3
Description
The FCRL3 (Fc receptor like 3) is a protein-coding gene located on chromosome 1.
Fc receptor-like protein 3 (FCRL3) is a protein encoded by the FCRL3 gene in humans. It belongs to the immunoglobulin receptor superfamily and is part of a group of Fc receptor-like glycoproteins located on the long arm of chromosome 1. FCRL3 contains both an immunoreceptor-tyrosine activation motif (ITAM) and an immunoreceptor-tyrosine inhibitory motif (ITIM) in its cytoplasmic domain, suggesting a role in regulating the immune system. Mutations in this gene have been linked to autoimmune diseases such as rheumatoid arthritis, autoimmune thyroid disease, and systemic lupus erythematosus. Structurally, FCRL3 is a type I transmembrane glycoprotein with an extracellular region, a transmembrane domain, and a cytoplasmic tail. Its extracellular region comprises five immunoglobulin-like domains that share varying degrees of homology with other Fc receptor-like proteins and Fc receptors FcγRI, FcγRII, and FcγRIII. The transmembrane region is composed of hydrophobic residues and is uncharged. The cytoplasmic region contains two signaling motifs: a membrane-proximal ITAM and a carboxy-proximal ITAM-like motif. The presence of both activating and inhibitory motifs hints at FCRL3's potential for dual signaling.
FCRL3 promotes B-cell proliferation, activation, and survival in response to TLR9 stimulation. It enhances NF-kappa-B and MAPK signaling pathways in TLR9-activated B-cells, but inhibits antibody production and suppresses plasma cell differentiation. FCRL3 also plays an inhibitory role in B-cell receptor (BCR)-mediated signaling, potentially through interactions with SH2 domain-containing phosphatases. This inhibition manifests as reduced tyrosine phosphorylation, calcium mobilization, and activation-induced cell death triggered by BCR signaling. In regulatory T-cells, FCRL3 expression is linked to a memory phenotype, reduced responsiveness to antigenic stimulation in the presence of IL2, and diminished capacity to suppress effector T-cell proliferation. Notably, FCRL3 acts as a human-specific epitope on the surface of oocytes (oolemma) and participates in sperm-egg adhesion and fusion. During fertilization, FCRL3 interacts with the IZUMO1-IZUMO1R/JUNO complex, displacing IZUMO1R/JUNO and acting as the new receptor for IZUMO1, enabling species-specific gamete fusion.
FCRL3 is also known as CD307c, FCRH3, IFGP3, IRTA3, MAIA, SPAP2.
