Histidine-rich glycoprotein, also known as HRG and HPRG, is a glycoprotein located in plasma and platelets, and contains an unusually large amount of histidine and proline. In human, five distinct domains are recognized in the mature HPRG molecule. There are two N-terminal cystatin-like modules (aa 19 - 254) and one His-Pro-rich region (aa 350 - 497) that is flanked by two Pro-rich segments (aa 276 - 321 and 498 - 525). The His-Pro-rich region contains 10 tandem repeats with an HHPHG motif, and the N- and C-termini are linked by a disulfide bond. The specific functions of HRG remain unclear, but it is known that the protein binds heme, dyes and divalent metal ions. It inhibits 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. HPRG is evolutionarily, functionally and structurally related to cleaved high molecular weight kininogen (HKa), an anti-angiogenic polypeptide that stimulates apoptosis of proliferating endothelial cells through binding to cell-surface tropomyosin. The antiangiogenic activity of the multidomain plasma protein HPRG is localized to its histidine-proline-rich (H/P) domain and has recently been shown to be mediated, at least partially, through binding to cell-surface tropomyosin in fibroblast growth factor-2-activated endothelial cells.
- Anti-Human HPRG/HRGP/HRG Antibody, Mouse MAb, Cat NO: 10836-MM01
- Anti-Human HPRG/HRGP/HRG Antibody, Mouse MAb, Cat NO: 10836-MM02
- Anti-Human HPRG/HRGP/HRG Antibody, Rabbit MAb, Cat NO: 10836-R028
- Anti-Human HPRG/HRGP/HRG Antibody, Rabbit PAb, Cat NO: 10836-RP03
- Anti-Human HPRG/HRGP/HRG Antibody, Rabbit PAb (Antigen Affinity Purified), Cat NO: 10836-RP04
HPRG ELISA Pair sets
HPRG cDNA Clones
HPRG, HRGP, HRG, DKFZp779H1622 [Homo sapiens]
Hprg, Hrgp, Hrg, AI265597, AW413091, D16jh2, D18020 [Mus musculus]
Entrez Gene summary for HRG:
This histidine-rich glycoprotein (HPRG) 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. HPRG 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 HRG gene lead to thrombophilia due to abnormal histidine-rich glycoprotein levels. [provided by RefSeq, Jul 2008]
Histidine-proline-rich glycoprotein, Short name=HPRG
The His-rich (HRR) region contains approximately 12 tandem internal repeats of the 5-residue G[H/P][H/P]PH consensus sequence. HRR binds heparan sulfate and possesses antiangiogenic, antibacterial and antifungal properties through binding Candida cells, and preferentially lysing the ergosterol-containing liposomes at low pH. The tandem repeats also bind divalent metal ions and heme.
HPRG contains 2 cystatin domains.
Proteolytic cleavage produces several HPRG fragments which are mostly disulfide-linked and, therefore, not released. Cleavage by plasmin is inhibited in the presence of heparin, zinc ions or in an acidic environment. Cleavage reduces binding of HPRG to heparan sulfate, but enhances the ability of HPRG to bind and tether plasminogen to the cell surface. On platelet activation, releases a 33 kDa antiangiogenic peptide which encompasses the HRR. Also cleaved in the C-terminal by plasmin.
HPRG interacts (via the HRR domain) with TPM1; the interaction appears to contribute to the antiangiogenic properties of the HRR domain. HPRG interacts with THBS2; the interaction blocks the antiangiogenic effect of THBS2 with CD36. HPRG interacts with THBS1 (via the TSP type I repeats); the interaction blocks the antiangiogenic effect of THBS1 with CD3. HPRG interacts with PLG (via its Kringle domains); the interaction tethers PLG to the cell surface and enhances its activation. Interacts with HPSE; the interaction is enhanced at acidic pH, partially inhibits binding of HPSE to cell surface receptors and modulates its enzymatic activity. Interacts (via the HRR domain) with TMP1; the interaction partially mediates the antiangiogenic properties of HPRG.
HPRG is expressed by the liver and secreted in plasma.
|Involvement in disease:||Defects in HRG are the cause of thrombophilia due to histidine-rich glycoprotein deficiency (THPH11) [MIM:613116]. A hemostatic disorder characterized by a tendency to thrombosis.|
General information above from UniProt
HPRG is plasma glycoprotein that binds a number of ligands such as heme, heparin, heparan sulfate, thrombospondin, plasminogen, and divalent metal ions. HPRG inhibits rosette formation. HPRG acts as an adapter protein and implicated in regulating many processes such as immune complex and pathogen clearance, cell adhesion, angiogenesis, coagulation and fibrinolysis. HPRG mediates clearance of necrotic cells through enhancing the phagocytosis of necrotic cells in an heparan sulfate-dependent pathway. This process can be regulated by the presence of certain HRG ligands such as heparin and zinc ions. HPRG binds to IgG subclasses of immunoglobins containing kappa and lambda light chains with different affinities regulating their clearance and inhibiting the formation of insoluble immune complexes. Tethers plasminogen to the cell surface. Tethers binds T-cells and alters the cell morphology. Tethers modulates angiogenesis by blocking the CD6-mediated antiangiongenic effect of thrombospondins, THBS1 and THBS2.
- HPRG plays a role in modulating coagulation and fibrinolysis
- HPRG has the unique property of selectively recognizing necrotic cells and may play an important physiological role by facilitating the uptake and clearance of necrotic, but not apoptotic, cells by phagocytes (Jones 2005)
- HPRG exerts antibacterial effects against Gram-positive bacteria (enterococcus faecalis and staphylococcus aureus) and Gram-negative bacteria (escherichia coli and pseudomonas aeruginosa) (Rydengard 2007)
- exert may assist in the maintenance of normal immune function by mediating the clearance of necrotic material, inhibiting the formation of insoluble immune complexes and enhancing their ability to activate complement, resulting in faster clearance (Manderson 2009)
|HRG, THPH11||Thrombophilia due to elevated HRG
Thrombophilia due to HRG deficiency
Phenotype Information for HPRG from OMIM (Online Mendelian Inheritance in Man)