Zinc-alpha 2-glycoprotein has ribonuclease activity

Arch Biochem Biophys. 1998 Jul 15;355(2):160-4. doi: 10.1006/abbi.1998.0735.


Zinc-alpha 2-glycoprotein (Zn alpha 2gp) 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 2gp has RNase activity, comparable to onconase but two orders of magnitude less than RNase A. The RNase activity of Zn alpha 2gp is characterized by maxima in pH at 7.5, in ionic strength at 50 mM NaCl, and in temperature at 60 degreesC. 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 2gp 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 2gp also has pyr 1, while RNase A does not. Alignment of the amino acid sequences of Zn alpha 2gp and onconase or RNase A reveals only modest matches. Despite the more substantial overall structural homology of Zn alpha 2gp to class I major histocompatibility complex proteins, Zn alpha 2gp 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.

MeSH terms

  • Enzyme Activation / drug effects
  • Epidermis / enzymology
  • Glycoproteins / antagonists & inhibitors
  • Glycoproteins / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Osmolar Concentration
  • Placental Hormones / pharmacology
  • Polyribonucleotides / metabolism
  • Prostate / enzymology
  • RNA, Fungal / metabolism
  • Ribonucleases / antagonists & inhibitors
  • Ribonucleases / metabolism*
  • Seminal Plasma Proteins*
  • Temperature


  • Glycoproteins
  • Placental Hormones
  • Polyribonucleotides
  • RNA, Fungal
  • Seminal Plasma Proteins
  • Zn-alpha-2-glycoprotein
  • placental ribonuclease inhibitor
  • Ribonucleases