Histidine Rich Glycoprotein (HRG)

HPRG; HRGP; Histidine-Proline Rich Glycoprotein; Thrombophilia Due To Elevated HRG

SPN	U315
HGNC	5181
MGI	2146636
PubMed	15748207
RGD	619808
UniProt	P04196
Wiki	HRG_(gene

This histidine-rich glycoprotein contains two cystatin-like domains and is located in plasma and platelets. The physiological function has not been determined but it is known that the protein binds heme, dyes and divalent metal ions. It can inhibit rosette formation and interacts with heparin, thrombospondin and plasminogen. Two of the protein's effects, the inhibition of fibrinolysis and the reduction of inhibition of coagulation, indicate a potential prothrombotic effect. Mutations in this gene lead to thrombophilia due to abnormal histidine-rich glycoprotein levels.This 'histidine-rich region' in the C terminus shows a high degree of similarity to the histidine-rich region of high molecular weight kininogen (HMWK); the N terminus shares sequence similarity with antithrombin III (AT3).

Reference

"Amino acid sequence of human histidine-rich glycoprotein derived from the nucleotide sequence of its cDNA."
Biochemistry 25:2220-2225(1986) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Evidence for the absence of intron H of the histidine-rich glycoprotein (HRG) gene: genetic mapping and in situ localization of HRG to chromosome 3q28-q29."
Genomics 19:195-197(1994) [PubMed] [Europe PMC] [Abstract]

"Plasma protein map: an update by microsequencing."
Electrophoresis 13:707-714(1992) [PubMed] [Europe PMC] [Abstract]

"Human serum histidine-rich glycoprotein. I. Interactions with heme, metal ions and organic ligands."
Biochim. Biophys. Acta 535:319-333(1978) [PubMed] [Europe PMC] [Abstract]

"Differential binding of histidine-rich glycoprotein (HRG) to human IgG subclasses and IgG molecules containing kappa and lambda light chains."
J. Biol. Chem. 274:29633-29640(1999) [PubMed] [Europe PMC] [Abstract]

"Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1."
J. Clin. Invest. 107:45-52(2001) [PubMed] [Europe PMC] [Abstract]

"Histidine-proline-rich glycoprotein has potent antiangiogenic activity mediated through the histidine-proline-rich domain."
Cancer Res. 62:5344-5350(2002) [PubMed] [Europe PMC] [Abstract]

"A fragment of histidine-rich glycoprotein is a potent inhibitor of tumor vascularization."
Cancer Res. 64:599-605(2004) [PubMed] [Europe PMC] [Abstract]

"Peptides derived from the histidine-proline domain of the histidine-proline-rich glycoprotein bind to tropomyosin and have antiangiogenic and antitumor activities."
Cancer Res. 64:5812-5817(2004) [PubMed] [Europe PMC] [Abstract]

"Histidine-rich glycoprotein binds to cell-surface heparan sulfate via its N-terminal domain following Zn2+ chelation."
J. Biol. Chem. 279:30114-30122(2004) [PubMed] [Europe PMC] [Abstract]

"Plasminogen is tethered with high affinity to the cell surface by the plasma protein, histidine-rich glycoprotein."
J. Biol. Chem. 279:38267-38276(2004) [PubMed] [Europe PMC] [Abstract]

"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]

"Minimal active domain and mechanism of action of the angiogenesis inhibitor histidine-rich glycoprotein."
Cancer Res. 66:2089-2097(2006) [PubMed] [Europe PMC] [Abstract]

"The anti-angiogenic His/Pro-rich fragment of histidine-rich glycoprotein binds to endothelial cell heparan sulfate in a Zn2+-dependent manner."
J. Biol. Chem. 281:10298-10304(2006) [PubMed] [Europe PMC] [Abstract]

"Regulation of histidine-rich glycoprotein (HRG) function via plasmin-mediated proteolytic cleavage."
Biochem. J. 424:27-37(2009) [PubMed] [Europe PMC] [Abstract]

"High affinity interaction between histidine-rich glycoprotein and the cell surface type ATP synthase on T-cells."
Biochim. Biophys. Acta 1788:1099-1107(2009) [PubMed] [Europe PMC] [Abstract]

"Histidine-rich glycoprotein and concanavalin A synergistically stimulate the phosphatidylinositol 3-kinase-independent signaling pathway in leukocytes leading to increased cell adhesion and changes in cell morphology."
Cell. Immunol. 259:5-12(2009) [PubMed] [Europe PMC] [Abstract]

"Probing the Cu(2+) and Zn(2+) binding affinity of histidine-rich glycoprotein."
J. Inorg. Biochem. 103:1634-1643(2009) [PubMed] [Europe PMC] [Abstract]

"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]

"Activated platelets provide a functional microenvironment for the antiangiogenic fragment of histidine-rich glycoprotein."
Mol. Cancer Res. 7:1792-1802(2009) [PubMed] [Europe PMC] [Abstract]

"Histidine-rich glycoprotein binds heparanase and regulates its enzymatic activity and cell surface interactions."
Int. J. Biochem. Cell Biol. 42:1507-1516(2010) [PubMed] [Europe PMC] [Abstract]

"Histidine-rich glycoprotein functions cooperatively with cell surface heparan sulfate on phagocytes to promote necrotic cell uptake."
J. Leukoc. Biol. 88:559-569(2010) [PubMed] [Europe PMC] [Abstract]

"Histidine-rich glycoprotein binds factor XIIa with high affinity and inhibits contact-initiated coagulation."
Blood 117:4134-4141(2011) [PubMed] [Europe PMC] [Abstract]

"HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF."
Cancer Cell 19:31-44(2011) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"HRG Tokushima: molecular and cellular characterization of histidine-rich glycoprotein (HRG) deficiency."
Blood 91:128-133(1998) [PubMed] [Europe PMC] [Abstract]

"Histidine-rich glycoprotein (HRG) Tokushima 2: novel HRG deficiency, molecular and cellular characterization."
Thromb. Haemost. 84:675-679(2000) [PubMed] [Europe PMC] [Abstract]