Zinc-α2-glycoprotein has ribonuclease activity

Zinc-alpha(2)-glycoprotein (Zn alpha(2)gp) is widely distributed in body fluids and in various epithelia; its gene has been completely sequenced, but its function has long remained elusive. We have found that Zn alpha(2)gp has RNase activity, comparable to onconase but two orders of magnitude less than RNase A The RNase activity of Zn alpha(2)gp is characterized by maxima in pH at 7.5, in ionic strength at 50 mM NaCl, and in temperature at 60 degrees C. It is strongly inhibited by ZnCl2, but unaffected by MgCl2. It is partially inactivated (down to 20%) by the placental RNase inhibitor. On synthetic polyribonucleotide substrates, the RNase activity of Zn alpha(2)gp is specific for pyrimidine residues [poly(C) and poly(U) equally] and cleaves only single-stranded RNA. For onconase, it has been demonstrated that the RNase activity depends on pyroglutamic acid (pyr 1) as the N-terminus; Zn alpha(2)gp also has pyr 1, while RNase A does not. Alignment of the amino acid sequences of Zn alpha(2)gp and onconase or RNase A reveals only modest matches. Despite the more substantial overall structural homology of Zn alpha(2)gp to class I major histocompatibility complex proteins, Zn alpha(2)gp has not been proven to be associated with the immune response and, conversely, we could not detect RNase activity in six class I HLA heavy chains. (C) 1998 Academic Press.