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Gene Review

HRG  -  histidine-rich glycoprotein

Homo sapiens

Synonyms: HPRG, HRGP, Histidine-proline-rich glycoprotein, Histidine-rich glycoprotein, THPH11
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Disease relevance of HRG


High impact information on HRG


Chemical compound and disease context of HRG


Biological context of HRG


Anatomical context of HRG

  • Thus, HRG has the unique property of selectively recognizing necrotic cells and may play an important physiological role in vivo by facilitating the uptake and clearance of necrotic, but not apoptotic, cells by phagocytes [9].
  • The binding characteristics of HRGP to T lymphocytes indicate a specific ligand-receptor interaction [14].
  • In this study, we show that HRG potentiates the ingestion of apoptotic cells by mature human monocyte-derived macrophages (HMDM) [15].
  • HRG bound specifically to apoptotic Jurkat cells and mature HMDM in a saturable and concentration-dependent manner [15].
  • HRG was also shown to significantly inhibit both FGF-stimulated and endogenous 3T3 cell DNA synthesis [16].

Associations of HRG with chemical compounds

  • Furthermore, blocking studies with various GAG species indicated that only heparin was a potent inhibitor of HRG binding [17].
  • In this study we have demonstrated that HRG also binds very strongly, in a heparan sulfate-independent manner, to cytoplasmic ligand(s) exposed in necrotic cells [9].
  • Histidine-rich glycoprotein (HRG) is an alpha2-glycoprotein found in mammalian plasma at high concentrations (approximately 150 microg/ml) and is distinguished by its high content of histidine and proline [17].
  • HRG binds to most cells primarily via heparan sulphate proteoglycans, binding which is also potentiated by elevated free Zn(2+) levels and low pH [18].
  • A reduced susceptibility to inhibition by chloride ions contributed to the higher activation rate of Glu-plasminogen on an HPRG surface [11].

Physical interactions of HRG


Regulatory relationships of HRG


Other interactions of HRG

  • Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1 [2].
  • In contrast, HPRG abrogates the stimulatory effects of fibrinogen on Plg activation in solution [10].
  • No correlation between HRGP level and t-PA-mediated plasminogen activation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)[3]
  • Structurally, HRG is a modular protein consisting of an N-terminal cystatin-like domain (N1N2), a central histidine-rich region (HRR) flanked by proline-rich sequences, and a C-terminal domain [17].
  • These data suggest that heparan sulfate is the predominate cell-surface ligand for HRG and that mammalian heparanase is a potential regulator of HRG binding [17].

Analytical, diagnostic and therapeutic context of HRG


  1. Histidine-rich glycoprotein and changes in the components of the fibrinolytic system after streptokinase therapy in patients with pulmonary thromboembolism. Goodnough, L.T., Saito, H., Bell, W.R., Heimburger, N. Am. J. Hematol. (1985) [Pubmed]
  2. Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1. Simantov, R., Febbraio, M., Crombie, R., Asch, A.S., Nachman, R.L., Silverstein, R.L. J. Clin. Invest. (2001) [Pubmed]
  3. Familial association of high levels of histidine-rich glycoprotein and plasminogen activator inhibitor-1 with venous thromboembolism. Angles-Cano, E., Gris, J.C., Loyau, S., Schved, J.F. J. Lab. Clin. Med. (1993) [Pubmed]
  4. Histidine-rich glycoprotein inhibits the antiproliferative effect of heparin on smooth muscle cells. Hajjar, D.P., Boyd, D.B., Harpel, P.C., Nachman, R.L. J. Exp. Med. (1987) [Pubmed]
  5. Modulation of heparin cofactor II activity by histidine-rich glycoprotein and platelet factor 4. Tollefsen, D.M., Pestka, C.A. J. Clin. Invest. (1985) [Pubmed]
  6. Serum histidine-rich glycoprotein levels are decreased in acquired immune deficiency syndrome and by steroid therapy. Morgan, W.T. Biochem. Med. Metab. Biol. (1986) [Pubmed]
  7. Histidine-proline-rich glycoprotein as a plasma pH sensor. Modulation of its interaction with glycosaminoglycans by ph and metals. Borza, D.B., Morgan, W.T. J. Biol. Chem. (1998) [Pubmed]
  8. Signal transduction in endothelial cells by the angiogenesis inhibitor histidine-rich glycoprotein targets focal adhesions. Lee, C., Dixelius, J., Thulin, A., Kawamura, H., Claesson-Welsh, L., Olsson, A.K. Exp. Cell Res. (2006) [Pubmed]
  9. Histidine-rich glycoprotein specifically binds to necrotic cells via its amino-terminal domain and facilitates necrotic cell phagocytosis. Jones, A.L., Poon, I.K., Hulett, M.D., Parish, C.R. J. Biol. Chem. (2005) [Pubmed]
  10. Effects of histidine-proline-rich glycoprotein on plasminogen activation in solution and on surfaces. Borza, D.B., Shipulina, N.V., Morgan, W.T. Blood Coagul. Fibrinolysis (2004) [Pubmed]
  11. Acceleration of plasminogen activation by tissue plasminogen activator on surface-bound histidine-proline-rich glycoprotein. Borza, D.B., Morgan, W.T. J. Biol. Chem. (1997) [Pubmed]
  12. Interaction of histidine-proline-rich glycoprotein with plasminogen: effect of ligands, pH, ionic strength, and chemical modification. Saez, C.T., Jansen, G.J., Smith, A., Morgan, W.T. Biochemistry (1995) [Pubmed]
  13. HRG Tokushima: molecular and cellular characterization of histidine-rich glycoprotein (HRG) deficiency. Shigekiyo, T., Yoshida, H., Matsumoto, K., Azuma, H., Wakabayashi, S., Saito, S., Fujikawa, K., Koide, T. Blood (1998) [Pubmed]
  14. Interaction of histidine-rich glycoprotein with human T lymphocytes. Saigo, K., Shatsky, M., Levitt, L.J., Leung, L.K. J. Biol. Chem. (1989) [Pubmed]
  15. Histidine-rich glycoprotein binds to DNA and Fc gamma RI and potentiates the ingestion of apoptotic cells by macrophages. Gorgani, N.N., Smith, B.A., Kono, D.H., Theofilopoulos, A.N. J. Immunol. (2002) [Pubmed]
  16. Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by acidic and basic fibroblast growth factor. Brown, K.J., Parish, C.R. Biochemistry (1994) [Pubmed]
  17. Histidine-rich glycoprotein binds to cell-surface heparan sulfate via its N-terminal domain following Zn2+ chelation. Jones, A.L., Hulett, M.D., Parish, C.R. J. Biol. Chem. (2004) [Pubmed]
  18. Histidine-rich glycoprotein: A novel adaptor protein in plasma that modulates the immune, vascular and coagulation systems. Jones, A.L., Hulett, M.D., Parish, C.R. Immunol. Cell Biol. (2005) [Pubmed]
  19. Histidine-rich glycoprotein blocks T cell rosette formation and modulates both T cell activation and immunoregulation. Shatsky, M., Saigo, K., Burdach, S., Leung, L.L., Levitt, L.J. J. Biol. Chem. (1989) [Pubmed]
  20. Histidine-rich glycoprotein binding to T-cell lines and its effect on T-cell substratum adhesion is strongly potentiated by zinc. Olsen, H.M., Parish, C.R., Altin, J.G. Immunology (1996) [Pubmed]
  21. Platelet thrombospondin forms a trimolecular complex with plasminogen and histidine-rich glycoprotein. Silverstein, R.L., Leung, L.L., Harpel, P.C., Nachman, R.L. J. Clin. Invest. (1985) [Pubmed]
  22. Regulation of complement functional efficiency by histidine-rich glycoprotein. Chang, N.S., Leu, R.W., Rummage, J.A., Anderson, J.K., Mole, J.E. Blood (1992) [Pubmed]
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