Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipids on the surface of damaged cells.
Beta2-glycoprotein I (beta2GPI) is a glycoprotein of unknown physiological function. It is the main target antigen for antiphospholipid antibodies in patients with antiphospholipid syndrome (APS). beta2GPI binds with high affinity to the atherogenic lipoprotein Lp(a) which shares structural homology with plasminogen, a key molecule in the fibrinolytic system. Impaired fibrinolysis has been described in APS. The present work reports the interaction between beta2GPI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta2GPI. In the process of Glu-Plasminogen activation, we found an increase in plasmin generation both at fibrin and cellular surface level as a function of the concentration of beta2GPI added, suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA. This phenomenon represents a novel regulatory step both in the positive feedback mechanism for extrinsic fibrinolysis and in antithrombotic regulation. IgG anti-beta2GPI antibodies recognized the beta2GPI at the endothelial surface inducing its activation with an increase of ICAM-I and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium. The interference in the plasmin conversion by anti-beta2GPI antibodies could generate thrombosis as observed in APS.
Interacting selectively and non-covalently with a glycoprotein, a protein that contains covalently bound glycose (monosaccharide) residues. These also include proteoglycans.
Evidence
1:
Inferred from Physical InteractionBHF-UCL
Lipoprotein(a) [Lp(a)], which has been shown to interact with fibrin(ogen) and other components of the blood clotting cascade, is a major independent risk factor for atherothrombotic disease in humans. The physiological function(s) of Lp(a), as well as the precise mechanism(s) by which high plasma levels of Lp(a) increase risk are unknown. Identification of further potential apo(a)-protein ligands may be crucial to illuminate apo(a)'s function(s) and pathophysiological properties. We used the repetitive apo(a) kringle IV type 2, which is variable in number in apo(a), to screen a human liver cDNA library by the yeast two-hybrid interaction trap system. Among 11 positive clones that emerged from the screen, eight clones were identified as beta-2 glycoprotein I and one as fibronectin. Coimmunoprecipitation experiments confirmed that beta-2 glycoprotein I and apo(a)/Lp(a) interact in human plasma and in cell culture supernatants of COS-1 cells, which ectopically expressed apo(a). The apo(a)-beta2-glycoprotein I interaction indicates new potential roles for Lp(a) in fibrinolysis and autoimmunity.
Interacting selectively and non-covalently with heparin, any member of a group of glycosaminoglycans found mainly as an intracellular component of mast cells and which consist predominantly of alternating alpha-(1->4)-linked D-galactose and N-acetyl-D-glucosamine-6-sulfate residues.
Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). We have recently found that CD4(+) T cells autoreactive to beta(2)GPI in patients with APS preferentially recognize a cryptic peptide encompassing amino acid residues 276-290 (p276-290), which contains the major PL-binding site, in the context of DR53. However, it is not clear how previously cryptic p276-290 becomes visible to the immune system and elicits a pathogenics autoimmune response to beta(2)GPI. Here we show that presentation of a disease-relevant cryptic T-cell determinant in beta(2)GPI is induced as a direct consequence of antigen processing from beta(2)GPI bound to anionic PL. Dendritic cells or macrophages pulsed with PL-bound beta(2)GPI induced a response of p276-290-specific CD4(+) T-cell lines generated from the patients in an HLA-DR-restricted and antigen-processing-dependent manner but those with beta(2)GPI or PL alone did not. In addition, the p276-290-reactive T-cell response was primed by stimulating peripheral blood T cells from DR53-carrying healthy individuals with dendritic cells bearing PL-bound beta(2)GPI in vitro. Our finding is the first demonstration of an in vitro mechanism eliciting pathogenic autoreactive T-cell responses to beta(2)GPI and should be useful in clarifying the pathogenesis of APS.
Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Evidence
1:
Inferred from Physical InteractionBHF-UCL
Beta2-glycoprotein I (beta2GPI) is a glycoprotein of unknown physiological function. It is the main target antigen for antiphospholipid antibodies in patients with antiphospholipid syndrome (APS). beta2GPI binds with high affinity to the atherogenic lipoprotein Lp(a) which shares structural homology with plasminogen, a key molecule in the fibrinolytic system. Impaired fibrinolysis has been described in APS. The present work reports the interaction between beta2GPI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta2GPI. In the process of Glu-Plasminogen activation, we found an increase in plasmin generation both at fibrin and cellular surface level as a function of the concentration of beta2GPI added, suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA. This phenomenon represents a novel regulatory step both in the positive feedback mechanism for extrinsic fibrinolysis and in antithrombotic regulation. IgG anti-beta2GPI antibodies recognized the beta2GPI at the endothelial surface inducing its activation with an increase of ICAM-I and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium. The interference in the plasmin conversion by anti-beta2GPI antibodies could generate thrombosis as observed in APS.
A protein activation cascade that contributes to blood coagulation and consists of the interactions among high molecular weight kininogen, prekallikrein, and factor XII that lead to the activation of clotting factor X.
The general hypothesis for the biological function of beta 2-glycoprotein I is that it neutralizes all negatively charged macromolecules that might enter the bloodstream and diminishes unwanted activation of the blood coagulation. In the present study we report that beta 2-glycoprotein I inhibits the activation of the contact phase system of the intrinsic pathway of blood coagulation. Activation was accomplished by an ellagic acid-phospholipid suspension (Cephotest) and measured by the appearance of amidolytic activity using the chromogenic substrate H-D-Pro-Phe-Arg-p-nitroanilide (S-2302). This inhibitory effect of beta 2-glycoprotein I was observed both when Cephotest was preincubated with beta 2-glycoprotein I and when the amount of beta 2-glycoprotein I in plasma was increased by addition of beta 2-glycoprotein I to either normal or beta 2-glycoprotein I-deficient plasma. The inhibitory effect of beta 2-glycoprotein I on the contact phase activation could be one of the physiological functions of this protein.
beta-2-Glycoprotein 1, an abundant plasma glycoprotein, binds anionic cell surfaces and functions as a regulator of thrombosis. Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis. In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells. The protein was without effect on preformed endothelial cell tubes. In vivo, the cleaved protein inhibited neovascularization into subcutaneously implanted Matrigel and Gelfoam sponge implants and the growth of orthotopically injected tumors. Collectively, these data indicate that plasmin-cleaved beta-2-glycoprotein 1 is a potent antiangiogenic and antitumor molecule of potential therapeutic significance.
The general hypothesis for the biological function of beta 2-glycoprotein I is that it neutralizes all negatively charged macromolecules that might enter the bloodstream and diminishes unwanted activation of the blood coagulation. In the present study we report that beta 2-glycoprotein I inhibits the activation of the contact phase system of the intrinsic pathway of blood coagulation. Activation was accomplished by an ellagic acid-phospholipid suspension (Cephotest) and measured by the appearance of amidolytic activity using the chromogenic substrate H-D-Pro-Phe-Arg-p-nitroanilide (S-2302). This inhibitory effect of beta 2-glycoprotein I was observed both when Cephotest was preincubated with beta 2-glycoprotein I and when the amount of beta 2-glycoprotein I in plasma was increased by addition of beta 2-glycoprotein I to either normal or beta 2-glycoprotein I-deficient plasma. The inhibitory effect of beta 2-glycoprotein I on the contact phase activation could be one of the physiological functions of this protein.
Any process that decreases the rate, frequency, or extent of the orderly movement of an endothelial cell into the extracellular matrix to form an endothelium.
beta-2-Glycoprotein 1, an abundant plasma glycoprotein, binds anionic cell surfaces and functions as a regulator of thrombosis. Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis. In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells. The protein was without effect on preformed endothelial cell tubes. In vivo, the cleaved protein inhibited neovascularization into subcutaneously implanted Matrigel and Gelfoam sponge implants and the growth of orthotopically injected tumors. Collectively, these data indicate that plasmin-cleaved beta-2-glycoprotein 1 is a potent antiangiogenic and antitumor molecule of potential therapeutic significance.
beta-2-Glycoprotein 1, an abundant plasma glycoprotein, binds anionic cell surfaces and functions as a regulator of thrombosis. Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis. In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells. The protein was without effect on preformed endothelial cell tubes. In vivo, the cleaved protein inhibited neovascularization into subcutaneously implanted Matrigel and Gelfoam sponge implants and the growth of orthotopically injected tumors. Collectively, these data indicate that plasmin-cleaved beta-2-glycoprotein 1 is a potent antiangiogenic and antitumor molecule of potential therapeutic significance.
Any process that stops, prevents, or reduces the frequency, rate or extent of fibrinolysis, an ongoing process that solubilizes fibrin, resulting in the removal of small blood clots.
BEta(2)-glycoprotein I (beta(2)-GPI) is proteolytically cleaved by plasmin in domain V (nicked beta(2)-GPI), being unable to bind to phospholipids. This cleavage may occur in vivo and elevated plasma levels of nicked beta(2)-GPI were detected in patients with massive plasmin generation and fibrinolysis turnover. In this study, we report higher prevalence of elevated ratio of nicked beta(2)-GPI against total beta(2)-GPI in patients with ischemic stroke (63%) and healthy subjects with lacunar infarct (27%) when compared to healthy subjects with normal findings on magnetic resonance imaging (8%), suggesting that nicked beta(2)-GPI might have a physiologic role beyond that of its parent molecule in patients with thrombosis. Several inhibitors of extrinsic fibrinolysis are known, but a negative feedback regulator has not been yet documented. We demonstrate that nicked beta(2)-GPI binds to Glu-plasminogen with K(D) of 0.37 x 10(-6) M, presumably mediated by the interaction between the fifth domain of nicked beta(2)-GPI and the fifth kringle domain of Glu-plasminogen. Nicked beta(2)-GPI also suppressed plasmin generation up to 70% in the presence of tissue plasminogen activator, plasminogen, and fibrin. Intact beta(2)-GPI lacks these properties. These data suggest that beta(2)-GPI/plasmin-nicked beta(2)-GPI controls extrinsic fibrinolysis via a negative feedback pathway loop.
beta(2)-Glycoprotein I (beta(2)-GPI) is a plasma glycoprotein with multifactorial relevance to clinical consequences. It was previously indicated that beta(2)-GPI can selectively bind to apoptotic cells. This study was designed to determine the role of beta(2)-GPI in apoptosis. Using an immunohistochemical study, we observed that beta(2)-GPI was co-localized with the apoptotic macrophages and smooth muscle cells (SMCs) of human coronary arteries. The contribution of beta(2)-GPI to apoptotic death was then investigated in vascular cells. Two nitric oxide (NO) donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl penicillamine (SNAP) were used in this study to trigger apoptosis in J774A.1 macrophages and human coronary artery smooth muscle cells (HCASMC). Cell viability was significantly improved in beta(2)-GPI-treated cells. It was also possible to detect a remarkable inhibitory effect by beta(2)-GPI on the NO-induced apoptosis by preventing nuclear shrinkage. Furthermore, the NO-induced apoptosis was associated with increase in caspase-3 activity and in the protein levels of caspase-3, c-Fos, and c-Jun. However, all these apoptosis-related events were inhibited in vascular cells treated with 200 microg/ml beta(2)-GPI. This is the first study to show that beta(2)-GPI may be important in the prevention of apoptosis in vascular cells.
beta(2)-Glycoprotein I (beta(2)-GPI) is a plasma glycoprotein with multifactorial relevance to clinical consequences. It was previously indicated that beta(2)-GPI can selectively bind to apoptotic cells. This study was designed to determine the role of beta(2)-GPI in apoptosis. Using an immunohistochemical study, we observed that beta(2)-GPI was co-localized with the apoptotic macrophages and smooth muscle cells (SMCs) of human coronary arteries. The contribution of beta(2)-GPI to apoptotic death was then investigated in vascular cells. Two nitric oxide (NO) donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl penicillamine (SNAP) were used in this study to trigger apoptosis in J774A.1 macrophages and human coronary artery smooth muscle cells (HCASMC). Cell viability was significantly improved in beta(2)-GPI-treated cells. It was also possible to detect a remarkable inhibitory effect by beta(2)-GPI on the NO-induced apoptosis by preventing nuclear shrinkage. Furthermore, the NO-induced apoptosis was associated with increase in caspase-3 activity and in the protein levels of caspase-3, c-Fos, and c-Jun. However, all these apoptosis-related events were inhibited in vascular cells treated with 200 microg/ml beta(2)-GPI. This is the first study to show that beta(2)-GPI may be important in the prevention of apoptosis in vascular cells.
The process in which inactive plasminogen is processed to active plasmin. This process includes cleavage at an internal Arg-Val site to form an N-terminal A-chain and C-terminal B-chain held together by a disulfide bond, and can include further proteolytic cleavage events to remove the preactivation peptide.
Beta2-glycoprotein I (beta2GPI) is a glycoprotein of unknown physiological function. It is the main target antigen for antiphospholipid antibodies in patients with antiphospholipid syndrome (APS). beta2GPI binds with high affinity to the atherogenic lipoprotein Lp(a) which shares structural homology with plasminogen, a key molecule in the fibrinolytic system. Impaired fibrinolysis has been described in APS. The present work reports the interaction between beta2GPI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta2GPI. In the process of Glu-Plasminogen activation, we found an increase in plasmin generation both at fibrin and cellular surface level as a function of the concentration of beta2GPI added, suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA. This phenomenon represents a novel regulatory step both in the positive feedback mechanism for extrinsic fibrinolysis and in antithrombotic regulation. IgG anti-beta2GPI antibodies recognized the beta2GPI at the endothelial surface inducing its activation with an increase of ICAM-I and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium. The interference in the plasmin conversion by anti-beta2GPI antibodies could generate thrombosis as observed in APS.
Beta2-glycoprotein I (beta2GPI) is a glycoprotein of unknown physiological function. It is the main target antigen for antiphospholipid antibodies in patients with antiphospholipid syndrome (APS). beta2GPI binds with high affinity to the atherogenic lipoprotein Lp(a) which shares structural homology with plasminogen, a key molecule in the fibrinolytic system. Impaired fibrinolysis has been described in APS. The present work reports the interaction between beta2GPI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta2GPI. In the process of Glu-Plasminogen activation, we found an increase in plasmin generation both at fibrin and cellular surface level as a function of the concentration of beta2GPI added, suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA. This phenomenon represents a novel regulatory step both in the positive feedback mechanism for extrinsic fibrinolysis and in antithrombotic regulation. IgG anti-beta2GPI antibodies recognized the beta2GPI at the endothelial surface inducing its activation with an increase of ICAM-I and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium. The interference in the plasmin conversion by anti-beta2GPI antibodies could generate thrombosis as observed in APS.
Any process that modulates the frequency, rate or extent of fibrinolysis, an ongoing process that solubilizes fibrin, resulting in the removal of small blood clots.
Beta2-glycoprotein I (beta2GPI) is a glycoprotein of unknown physiological function. It is the main target antigen for antiphospholipid antibodies in patients with antiphospholipid syndrome (APS). beta2GPI binds with high affinity to the atherogenic lipoprotein Lp(a) which shares structural homology with plasminogen, a key molecule in the fibrinolytic system. Impaired fibrinolysis has been described in APS. The present work reports the interaction between beta2GPI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta2GPI. In the process of Glu-Plasminogen activation, we found an increase in plasmin generation both at fibrin and cellular surface level as a function of the concentration of beta2GPI added, suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA. This phenomenon represents a novel regulatory step both in the positive feedback mechanism for extrinsic fibrinolysis and in antithrombotic regulation. IgG anti-beta2GPI antibodies recognized the beta2GPI at the endothelial surface inducing its activation with an increase of ICAM-I and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium. The interference in the plasmin conversion by anti-beta2GPI antibodies could generate thrombosis as observed in APS.
The chemical reactions and pathways involving triglyceride, any triester of glycerol. The three fatty acid residues may all be the same or differ in any permutation. Triglycerides are important components of plant oils, animal fats and animal plasma lipoproteins.
The directed movement of triglyceride into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Triglycerides are important components of plant oils, animal fats and animal plasma lipoproteins.
Evidence
1:
Inferred from Sequence or Structural SimilarityBHF-UCL
Seven rats were infused with 14C-labeled Intralipid at a constant rate of 0.38 ml per hour over a time period of 4 hours. Four rats served as controls and received an infusion of 0.15 M NaCl or of serum albumin two hours after the start of the experiment. In these animals the plasma triglyceride concentration rose linearly from 30 to 240 min and paralleled the total blood radioactivity. The triglyceride concentrations at the end of the experiments were about 25 times as high as at the beginning. Three rats receiving 2 hr after the start an additional infusion of beta 2-glycoprotein-I at a rate of 10 mg per hr showed a markedly enhanced triglyceride removal from the plasma, reaching a steady state which lasted for more than 30 min. It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
My favorites 
My labels 
Login
