6533b83afe1ef96bd12a77bf

RESEARCH PRODUCT

Posttranslational Processing of Human α2-HS Glycoprotein (Human Fetuin)

subject

description

α2-HS glycoprotein (α2-HS) is a major protein occuring in human blood and calciferous tissues. Due to extensive sequence identity, α2-HS has been grouped with the fetuins, a family of proteins that occur in fetal plasma in high concentrations. Native α2-HS undergoes a series of posttranslational modifications including proteolytic processing, multiple N-glycosylations and O-glycosylations, and sulfation of the carbohydrate side chains. Various two-chain forms of α2-HS have been prepared from human plasma, however, the single-chain precursor has not yet been isolated. Here, we have studied the biosynthesis of α2-HS by a human hepatoma cell line, HepG2. We demonstrate that a single-chain form and the two-chain form of α2-HS are secreted by this cell line. The α2-HS forms are further modified by phosporylation on multiple serine residues. Mapping studies indicate that the connecting peptide region releasable from the heavy chain of α2-HS contains at least one such Phosphorylation site. Our results identify proteolytic trimming and/or phosphorylation as modifications possibly regulating the biological effects of α2-HS and the homologous fetuins.