ASGR2 Human
Description
Molecular Characterization of ASGR2
ASGR2 is a minor subunit of ASGPR, encoded by the ASGR2 gene (CLEC4H2). It forms hetero-oligomers with ASGR1 (the major subunit) to mediate ligand binding and endocytosis .
Biological Functions
ASGR2 contributes to:
-
Glycoprotein Clearance: Mediates endocytosis of desialylated glycoproteins (e.g., von Willebrand factor) via galactose/N-acetylgalactosamine recognition .
-
Viral Entry: Facilitates hepatic infection by hepatitis B and other viruses .
-
Thrombopoietin Regulation: Modulates platelet homeostasis through glycoprotein interactions .
Expression and Localization
-
Extrahepatic Expression: Detected in monocytes, thyroid, and gastric tissues .
-
Cellular Distribution: Colocalizes with ASGR1 on hepatocyte membranes but can traffic independently in monocytes .
Transcript Variants and Isoforms
-
Splice variants (e.g., H2b, H2c) form distinct hetero-oligomers with ASGR1, altering ligand affinity .
-
Monocytes express correctly spliced ASGR2 transcripts at levels 4–6 orders lower than hepatocytes .
Ligand Binding Dynamics
-
Affinity Factors:
Table 2: ASGR2 Ligand Binding Parameters
| Ligand Type | Dissociation Constant (Kd) | Key Interaction |
|---|---|---|
| Monovalent Galactose | ~10⁻³ M | Low affinity |
| Tri-GalNAc | ED₅₀: 0.15–0.9 µg/mL | High affinity |
| N-Acetylgalactosamine | 10⁻⁶ M | Moderate affinity |
Clinical Implications
-
Therapeutic Targeting: ASGR2 is exploited for liver-specific drug delivery (e.g., siRNA conjugates) .
-
Disease Associations:
Recombinant ASGR2 in Research
Product Specs
Product Science Overview
Asialoglycoprotein Receptor 2 (ASGR2) is a crucial component of the asialoglycoprotein receptor (ASGPR) system, primarily found in the liver. This receptor plays a significant role in the clearance of glycoproteins from the bloodstream. ASGR2, along with its counterpart ASGR1, forms a hetero-oligomeric complex that mediates the endocytosis and lysosomal degradation of glycoproteins with exposed terminal galactose or N-acetylgalactosamine residues .
ASGR2 is a transmembrane protein that is localized to the endoplasmic reticulum and plasma membrane . It is composed of a major 48 kDa subunit (ASGR1) and a minor 40 kDa subunit (ASGR2) . The receptor is responsible for recognizing and binding to desialylated glycoproteins, facilitating their internalization and subsequent degradation in lysosomes .
ASGR2 is predominantly expressed in hepatocytes, the main functional cells of the liver . The receptor’s expression is regulated by various factors, including hormonal and nutritional states. It plays a vital role in maintaining serum glycoprotein homeostasis by removing glycoproteins that have lost their terminal sialic acid residues .
Recent studies have identified splice variants of ASGR2, which may have different functional roles in hepatocytes . These variants could provide insights into the receptor’s diverse functions and its involvement in liver diseases. Recombinant forms of ASGR2 are used in research to study its structure, function, and potential therapeutic applications.
