FCGR3A
Description
The FCGR3A (Fc gamma receptor IIIa) is a protein-coding gene located on chromosome 1.
Low affinity immunoglobulin gamma Fc region receptor III-A is a protein that in humans is encoded by the FCGR3A gene. It is also known as CD16a as it is part of the cluster of differentiation cell surface molecules.
FCGR3A, also known as CD16a, is a receptor that binds to the Fc fragment of immunoglobulin G (IgG). It plays a crucial role in antibody-dependent cellular cytotoxicity (ADCC), a process where immune cells, particularly natural killer (NK) cells, destroy antibody-coated target cells. FCGR3A is optimally activated upon binding of clustered antigen-IgG complexes displayed on cell surfaces. It does not bind to free monomeric IgG, preventing inappropriate effector cell activation. FCGR3A mediates IgG effector functions on NK cells, triggering cytokine production and degranulation, and contributing to the generation of memory-like adaptive NK cells. It also regulates NK cell survival and proliferation. FCGR3A associates with adapter proteins CD247 and FCER1G to form functional signaling complexes. Upon engagement of antigen-IgG complexes, FCGR3A triggers phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs), activating phosphatidylinositol 3-kinase signaling and elevating intracellular calcium, leading to NK cell activation. It can also costimulate NK cells and trigger target cell lysis independently of IgG binding. FCGR3A mediates the antitumor activities of therapeutic antibodies, and triggers TNFA-dependent ADCC of IgG-coated tumor cells on monocytes. It enhances ADCC in response to afucosylated IgGs. FCGR3A plays a role in Dengue virus pathogenesis via antibody-dependent enhancement (ADE), where afucosylated non-neutralizing IgG1s bind to FCGR3A, facilitating virus entry into myeloid cells. FCGR3A forms heterooligomeric complexes with ITAM-containing signaling subunits, interacting with these subunits via its transmembrane domain. This interaction is crucial for receptor complex expression on the cell surface and intracellular signal transduction. FCGR3A binds the Fc region of antigen-complexed IgG with a preference for IgG1 and IgG3 isotypes. It interacts with CD2, contributing to NK cell activation and cytotoxicity, and interacts with S100A4, inhibiting PKC-dependent phosphorylation of FCGR3A.
FCGR3A is also known as CD16, CD16-II, CD16A, FCG3, FCGR3, FCGRIII, FCR-10, FCRIII, FCRIIIA, FcGRIIIA, IGFR3, IMD20.
