Histidine-rich glycoprotein: the Swiss Army knife of mammalian plasma.
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.
The John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Ivan K H
IK
Poon
Kruti K
KK
Patel
David S
DS
Davis
Christopher R
CR
Parish
Mark D
MD
Hulett
D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology; D001798:Blood Proteins / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D018450:Disease Progression; D004731:Endotoxins / Q000037:antagonists & inhibitors; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D009369:Neoplasms / Q000097:blood / Q000209:etiology; D018919:Neovascularization, Physiologic; D011506:Proteins / Q000276:immunology / Q000502:physiology*; D017452:Receptors, IgG / Q000097:blood; D000099053:Histidine-Rich Glycoprotein
D000936:Antigen-Antibody Complex; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D011506:Proteins; D017452:Receptors, IgG; D000099053:Histidine-Rich Glycoprotein