Alternative titles; symbols
HGNC Approved Gene Symbol: ASGR2
Cytogenetic location: 17p13.1 Genomic coordinates (GRCh38): 17:7,101,322-7,115,146 (from NCBI)
The ASGR2 gene encodes a glycoprotein that forms the asialoglycoprotein receptor, also known as the Ashwell receptor, which is specific for desialylated (galactosyl-terminal) glycoproteins and is expressed exclusively in hepatic parenchymal cells (Spiess and Lodish, 1985).
See also ASGR1 (108360).
From the same cDNA library that was made from the human hepatoma cell line HepG2 and was used to isolate ASGR1, Spiess and Lodish (1985) isolated and sequenced a clone encoding a second asialoglycoprotein receptor, which they referred to as H2 and which had protein sequence homology of 58% to H1. The rat similarly has 2 ASG receptors, R1 and R2. Spiess and Lodish (1985) found that H1 is more homologous to R1 than to H2, and H2 is more homologous to R2 than to H1. Thus, the 2 receptor genes evolved before the separation of rat and man. Spiess and Lodish (1985) identified 2 versions of H2 cDNA, differing only by the presence or absence of a segment of 15 bp within the coding region. They interpreted this as reflecting differential splicing of an intron.
Grewal et al. (2008) found that platelet deficiency associated with St3gal4 (104240) deficiency and disruption of sialyltransferase function was restored in Asgr1- or Asgr2-deficient mice. The studies suggested that ST3GAL4 deficiency exposes endogenous glycan ligands on platelets that are recognized by the Ashwell receptor in an interaction that promotes asialo-platelet clearance by hepatocytes and leads to thrombocytopenia. Wildtype mice infected with Streptococcus pneumoniae, a pathogen with sialidase (neuraminidase) activity, showed progressively desialylated platelets and thrombocytopenia due to increased removal of platelets from the circulation by the hepatic Ashwell receptor. Asgr1- or Asgr2-deficient mice who were infected showed decreased survival and signs of severe disseminated intravascular coagulation compared to infected wildtype mice, with the outcome worse for Asgr1-deficient mice. Grewal et al. (2008) concluded that the thrombocytopenia in disseminated intravascular coagulation results from Ashwell receptor-dependent clearance of platelets that are first desialylated by the sialidase of the pathogen. The findings revealed that von Willebrand factor (VWF; 613160) and platelets are endogenous ligands of the Ashwell receptor, implying that hepatocytes are involved in the clearance of these coagulation factors from the circulation, which is an unexpected biologic activity for this cell type.
Grewal, P. K., Uchiyama, S., Ditto, D., Varki, N., Le, D. T., Nizet, V., Marth, J. D. The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nature Med. 14: 648-655, 2008. [PubMed: 18488037] [Full Text: https://doi.org/10.1038/nm1760]
Spiess, M., Lodish, H. F. Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution. Proc. Nat. Acad. Sci. 82: 6465-6469, 1985. [PubMed: 3863106] [Full Text: https://doi.org/10.1073/pnas.82.19.6465]