New insights into the functions of histidine-rich glycoprotein

Histidine-rich glycoprotein (HRG) is one of the major plasma proteins; it has been isolated from the plasma of various mammals and chicken. HRG has a multidomain structure consisting of cystatin-like domains 1 and 2, Pro-rich domain 1, His-rich domain, Pro-rich domain 2, and C-terminal domain from its N-terminus. The ability to bind a wide range of ligands suggests the multivalent function of HRG in blood coagulation, fibrinolysis, and innate immune systems. The local structure supports its binding capacities. Herein, the structural characteristics of HRG and its gene structure are described first. The functions of HRG in coagulation and fibrinolysis systems, the recently reported functions of HRG in angiogenesis, and HRG's antibacterial effect are described next. The activities of HRG in immune response are also reviewed.