Histidine-rich glycoprotein: the Swiss Army knife of mammalian plasma

Blood. 2011 Feb 17;117(7):2093-101. doi: 10.1182/blood-2010-09-303842. Epub 2010 Oct 22.


Histidine-rich glycoprotein (HRG), also known as histidine-proline-rich glyco-protein, is an abundant and well-characterized protein of vertebrate plasma. HRG has a multidomain structure that allows the molecule to interact with many ligands, including heparin, phospholipids, plasminogen, fibrinogen, immunoglobulin G, C1q, heme, and Zn²(+). The ability of HRG to interact with various ligands simultaneously has suggested that HRG can function as an adaptor molecule and regulate numerous important biologic processes, such as immune complex/necrotic cell/pathogen clearance, cell adhesion, angiogenesis, coagulation, and fibrinolysis. The present review covers the proposed multifunctional roles of HRG with a focus on recent findings that have led to its emergence as a key regulator of immunity and vascular biology. Also included is a discussion of the striking functional similarities between HRG and other important multifunctional proteins found in plasma, such as C-reactive protein, C1q, β₂ glycoprotein I, and thrombospondin-1.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen-Antibody Complex / blood
  • Antimicrobial Cationic Peptides / blood
  • Blood Coagulation / physiology
  • Blood Proteins / immunology
  • Blood Proteins / physiology*
  • Cell Adhesion / physiology
  • Cell Death / physiology
  • Disease Progression
  • Endotoxins / antagonists & inhibitors
  • Fibrinolysis / physiology
  • Humans
  • Immunity, Innate
  • Neoplasms / blood
  • Neoplasms / etiology
  • Neovascularization, Physiologic
  • Proteins / immunology
  • Proteins / physiology*
  • Receptors, IgG / blood


  • Antigen-Antibody Complex
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Endotoxins
  • Proteins
  • Receptors, IgG
  • histidine-rich proteins