The Fc receptor with low affinity for IgG (FCGR3, or CD16) is encoded by 2 nearly identical genes, FCGR3A and FCGR3B, resulting in tissue-specific expression of alternative membrane-anchored isoforms. FCGR3A, it is also known as CD16a, encodes a transmembrane protein expressed on activated monocytes/macrophages, natural killer (NK) cells, and a subset of T cells. CD16a / FCGR3A is a receptor expressed on NK cells that facilitates antibody dependent cellular cytotoxicity (ADCC) by binding to the Fc portion of various antibodies. CD16a / FCGR3A also has a broader function. CD16a / FCGR3A is directly involved in the lysis of some virus-infected cells and tumor cells by NK cells, independent of antibody binding. Cross-linking of CD16a / FCGR3A on NK cells resulted in increased intracellular Ca2+ levels and a cascade of biochemical events similar to those activated by the T cell receptor. CD16a / FCGR3A on human NK cells is a lysis receptor that mediates the direct killing of some virus infected and tumor cells, independent of antibody ligation.
Receptors for the Fc region of immunoglobin G (FcγR) are divided into three classes and FcγRIII is a multifunctional; low/intermediate affinity receptor. In humans; FcγRIII is expressed as two distinct forms (FcγRIIIA and FcγRIIIB) that are encoded by two different but highly homologous genes in a cell type-specific manner. FcγRIIIB is a low-affinity; GPI-linked receptor expressed by neutrophils and eosinophils; whereas FcγRIIIA is an intermediate affinity polypeptide-anchored transmembrane glycoprotein expressed by a subset of T lymphocytes; natural killer (NK) cells; monocytes; and macrophages. The FcγRIIIA receptor is involved in phagocytosis; secretion of enzymes; inflammatory mediators; antibody-dependent cellular cytotoxicity (ADCC); mast cell degranulation; and clearance of immune complexes. FcγRIIIA has an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain and delivers an activation signal in the immune responses. Aberrant expression or mutations in this gene is implicated in susceptibility to recurrent viral infections; systemic lupus erythematosus; and alloimmune neonatal neutropenia. In humans; it is a 50 -70 kD type I transmembrane activating receptor. The FcγRIIIA cDNA encodes 254 amino acid including a 16aa signal sequence; 191 amino acid ECD with two C2-type Ig-like domains; five potential N-glycosylation sites; a 22 amino acid transmembrane sequence and a 25 amino acid cytoplasmic domain.
Receptors for the Fc region of immunoglobin G (FcγR) are divided into three classes and FcγRIII is a multifunctional; low/intermediate affinity receptor. In humans; FcγRIII is expressed as two distinct forms (FcγRIIIA and FcγRIIIB) that are encoded by two different but highly homologous genes in a cell type-specific manner. FcγRIIIB is a low-affinity; GPI-linked receptor expressed by neutrophils and eosinophils; whereas FcγRIIIA is an intermediate affinity polypeptide-anchored transmembrane glycoprotein expressed by a subset of T lymphocytes; natural killer (NK) cells; monocytes; and macrophages. The FcγRIIIA receptor is involved in phagocytosis; secretion of enzymes; inflammatory mediators; antibody-dependent cellular cytotoxicity (ADCC); mast cell degranulation; and clearance of immune complexes. FcγRIIIA has an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain and delivers an activation signal in the immune responses. Aberrant expression or mutations in this gene is implicated in susceptibility to recurrent viral infections; systemic lupus erythematosus; and alloimmune neonatal neutropenia. In humans; it is a 50 -70 kD type I transmembrane activating receptor.
The asialoglycoprotein receptor (ASGPR), an endocytotic cell surface receptor expressed by hepatocytes, is triggered by triantennary binding to galactose residues of macromolecules such as asialoorosomucoid (ASOR). ASGPR belongs to the long-form subfamily of the C-type/Ca2+ dependent lectin family. It is a complex of two noncovalently-linked and highly homologous subunits, a major 42 kDa glycoprotein ASGPR1(MHL-1) and a minor 51 kDa glycoprotein ASGR2 (MHL-2). ASGPR1 is synthesized as a type II transmembrane protein that contains a cytosolic N-terminal domain, a single transmembrane segment, and an extracellular domain which contains two important structural regions. The first is a stalk domain that contributes to noncovalent oligomerization, and the second is a Ca2+-dependent carbohydrate binding domain at the very C-terminus that is unusually stabilized by three ions. The research regarded that ASGPR1 could be targeted for anti- hepatitis B virus (HBV) drug development.
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