Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Outer renal medulla calmodulin-binding proteins from a soluble protein fraction and a plasma membrane fraction solubilized in CHAPS were retained on a calmodulin-Sepharose 4B column in the presence of Ca2+, and subsequently eluted by EGTA. The calmodulin-binding proteins constituted 2.5% of the soluble protein and 0.1% of the solubilized membrane protein. beta2-glycoprotein I was identified as a calmodulin-binding protein both by N-terminal sequencing and by immunoblotting. Quantification showed that beta2-glycoprotein I constituted the major part (approx. 35%) of the calmodulin-binding membrane proteins, but only a minor part (approx. 0.1%) of the calmodulin-binding proteins in the soluble fraction. These results show for the first time that beta2-glycoprotein I binds calmodulin and that beta2-glycoprotein I may in kidney be a membrane-associated protein. Immunohistochemical studies identified beta2-glycoprotein I in several parts of the cortex and the medulla of the kidney, including Bowman's capsula, the tubular lumen and the tubular epithelium, indicating that beta2-glycoprotein I, despite its relatively high molecular mass, is filtrated in the glomerulus and subsequently reabsorbed by the tubular epithelium. This is in agreement with beta2-glycoprotein I being a marker for renal tubular disease.
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PMID:Identification of beta2-glycoprotein I as a membrane-associated protein in kidney: purification by calmodulin affinity chromatography. 918 40

beta2-Glycoprotein I was shown to bind reversibly to calmodulin in a Ca2+-dependent manner with a 1:1 stoichiometry, a Kd of 3 x 10(-9) M and a Hill coefficient of 1.4. A sequence in beta2-glycoprotein I (Lys-Pro-Gly-Tyr-Val-Ser-Arg-Gly-Gly-Met-Arg-Lys-Phe-Ile-) limited by Cys-32 and Cys-47 is suggested to be the calmodulin-binding region. This sequence was the only one in beta2-glycoprotein I theoretically having the ability to form a basic amphiphilic alpha-helix typical of a calmodulin binding sequence. The peptide corresponding to this sequence was synthesized and found to inhibit the interaction between beta2-glycoprotein I and calmodulin with an IC50 value of 0.38 x [beta2-glycoprotein I] and to displace the beta2-glycoprotein I from the beta2-glycoprotein I/calmodulin complex with an IC50 value of 0.90 x [beta2-glycoprotein I].
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PMID:Characterization of the interaction between beta2-glycoprotein I and calmodulin, and identification of a binding sequence in beta2-glycoprotein I. 918 41

Screening of serum by using a surface plasmon resonance analysis assay identified beta2-glycoprotein-I/apolipoprotein H as a plasma component binding to the renal epithelial endocytic receptor megalin. A calcium-dependent megalin-mediated beta2-glycoprotein-I endocytosis was subsequently demonstrated by ligand blotting of rabbit renal cortex and uptake analysis in megalin-expressing cells. Immunohistochemical and immunoelectron microscopic examination of kidneys and the presence of high concentrations of beta2-glycoprotein-I in urine of mice with disrupted megalin gene established that megalin is the renal clearance receptor for beta2-glycoprotein-I. A significant increase in functional affinity for purified megalin was observed when beta2-glycoprotein-I was bound to the acidic phospholipids, phosphatidylserine and cardiolipin. The binding of beta2-glycoprotein-I and beta2-glycoprotein-I- phospholipid complexes to megalin was completely blocked by receptor-associated protein. In conclusion, we have demonstrated a novel receptor recognition feature of beta2-glycoprotein-I. In addition to explaining the high urinary excretion of beta2-glycoprotein-I in patients with renal tubule failure, the data provide molecular evidence for the suggested function of beta2-glycoprotein-I as a linking molecule mediating cellular recognition of phosphatidylserine-exposing particles.
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PMID:beta2-glycoprotein-I (apolipoprotein H) and beta2-glycoprotein-I-phospholipid complex harbor a recognition site for the endocytic receptor megalin. 972 58

The plasma protein beta2-glycoprotein I (beta2-GPI) is a major target of autoantibodies in patients with the antiphospholipid syndrome. To understand the physiological function of beta2-GPI and its potential role in the pathophysiology of the antiphospholipid syndrome, the binding of beta2-GPI to phospholipid membranes was characterized. The interaction of beta2-GPI with unilamellar vesicles containing varying amounts of acidic phospholipids with phosphatidylcholine (PC) was measured at equilibrium via relative light scattering. Analysis of binding isotherms gave apparent Kd values ranging from approximately 5.0 to 0.5 microM over a range of 5-20 mol % anionic phospholipid. Inhibition of binding by increasing ionic strength and Ca2+ ions suggests that binding is primarily electrostatic. These data indicate that beta2-GPI binding to membranes with physiological anionic phospholipid content is relatively weak in comparison to plasma coagulation proteins, suggesting that beta2-GPI does not function as a physiological anticoagulant based on its phospholipid-binding properties.
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PMID:Characterization of beta2-glycoprotein I binding to phospholipid membranes. 979 80

We report the case of a young woman with primary antiphospholipid syndrome (APS), which presented with acute renal failure, hypoproteinemia, hypoalbuminemia and nephrotic proteinuria. Investigations showed total infarction of right kidney by extensive arterial and vein thrombosis and presence of anticardiolipin antibodies IgG isotype (anti-beta2-glycoprotein I-positive). She was submitted to right nefrectomy and initiated anticoagulant therapy. After nefrectomy, the postoperative period was marked by the development of arterial hypertension and persistence of nephrotic syndrome. Hypertension was treated with antihypertensive drugs (IECA, beta-blocker and calcium antagonist). As the nephrotic syndrome persisted despite anticoagulant and antihypertensive therapy, the patient was treated with oral corticosteroids. Her renal function improved, hypoproteinemia and hypoalbuminemia corrected to normal values and proteinuria decreased to subnephrotic value. We discuss the unusual presentation of this case of primary antiphospholipid syndrome with total unilateral renal thrombosis and nephrotic syndrome that respond to anticoagulant, antihypertensive and corticosteroid therapy.
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PMID:Primary antiphospholipid syndrome presented by total infarction of right kidney with nephrotic syndrome. 1044 98

Prothrombin time (PT) is routinely used to monitor oral anticoagulant treatment in patients with the antiphospholipid antibody syndrome (APS). The fact that PT is a phospholipid (PL)-dependent coagulation test raises the possibility that lupus anticoagulant (LA) might interfere with this test, thus complicating the control of anticoagulant treatment. The effect of 6 affinity-purified preparations of anti- (a)beta2-glycoprotein I (GPI) antibodies with LA activity on the PT was tested. Instead of prolonging PT as expected, the abeta2-GPI antibodies reduced the PT of both normal plasma and anticoagulated plasma by a mean of 2.4 seconds and 5.6 seconds, respectively. This effect was also observed using other 5 commercially available preparations of thromboplastin. The abeta2-GPI-mediated reduction in PT was dose-dependent and was lost upon removal of beta2-GPI. The failure of abeta2-GPI antibodies to express LA activity in PT was found to depend on the fact that calcium ions were added together with PL at the beginning of the assay. In fact, modification of the standard diluted Russell viper venom time (dRVVT) test by adding calcium ions together with PL resulted in a loss of abeta2-GPI anticoagulant activity. The procoagulant effect was not as evident in an assay that used stimulated monocytes as a source of thromboplastin. These results show that abeta2-GPI antibodies exhibit an 'in vitro' procoagulant effect in PT and an anticoagulant effect in dRVVT only when the interaction with their antigen and PL occurs in the absence of calcium ions.
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PMID:Procoagulant effect of anti-beta2-glycoprotein I antibodies with lupus anticoagulant activity. 1057 96

We have investigated beta2-glycoprotein I (beta2GPI) binding to platelet-derived microparticles (PMP) and its effect on GPIIb/IIIa. PMP were isolated from washed human platelets after stimulation with A23187, and analyzed by surface plasmon resonance spectroscopy. Beta2GPI as well as activated protein C (APC) or annexin V bound to PMP-coated sensorchips, demonstrating exposure of anionic phospholipids on immobilized PMP. Beta2GPI binding was impaired by calcium and occurred in a concentration-dependent manner with apparent k(on) = 2.6 x 10(4) M(-1) s(-1) and k(off) = 4.4 x 10(-3) s(-1), corresponding to a KD value of 1.7 x 10(-7) M. When analyzed by flow cytometry, the binding of certain mAbs specific for GPIIb and/or GPIIIa was reduced in the presence of beta2GPI but not of APC or annexin V, whereas the binding of anti-GPIb or anti-P-selectin mAbs, or of soluble fibrinogen remained unchanged. These results suggest a broad but specific influence of beta2GPI on GPIIb/IIIa immunoreactivity, and indicate that beta2GPI may act as a modulator of GPIIb/IIIa-dependent functions of PMP.
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PMID:Beta2-glycoprotein I binding to platelet microparticle membrane specifically reduces immunoreactivity of glycoproteins IIb/IIIa. 1124 54

Patients with the anti-phospholipid syndrome (APS) have antiphospholipid antibodies (aPA) which are often targeted towards phospholipid binding proteins such as beta2-glycoprotein I and prothrombin. Antibodies to factor XII (FXIIabs) have also been identified in some patients with APS. Factor XII (FXII) is a member of the kringle family of proteins which include plasminogen and prothrombin. Antibodies to prothrombin have been associated with myocardial infarction and have been shown to cross react with plasminogen. Sixteen patients with APS and FXIIabs were investigated for the presence of antibodies to prothrombin, by enzyme linked immunosorbent assay in a calcium (Ca++) independent assay. All sixteen showed different antibody binding patterns than those observed for antibodies to FXII. Eight patients were further investigated using surface plasmon resonance (SPR) for antibody binding to covalently bound FXII and to covalently bound prothrombin in both Ca++ dependent and independent systems. Of three patients demonstrating antibody binding to FXII by SPR, none demonstrated antibody binding to prothrombin in a Ca++ independent system with one demonstrating antibody binding to prothrombin that was Ca++ dependent. Of five patients who did not bind FXII by SPR, one demonstrated antibody binding to prothrombin in a Ca++ independent system while two demonstrated antibody binding to prothrombin in a Ca++ dependent system. Antibodies to FXII in patients with APS appear to be distinct from antibodies to prothrombin.
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PMID:Antibodies to factor XII are distinct from antibodies to prothrombin in patients with the anti-phospholipid syndrome. 1191 74

The hemostatic process is tightly regulated by several antithrombotic mechanisms. Among them, protein Z (PZ)-dependent protease inhibitor (ZPI) potently inhibits factor (F)Xa in a manner dependent on calcium ions, phospholipids and PZ. Autoimmune antiphospholipid antibodies (aPL) are mainly directed against phospholipid-binding plasma proteins such as beta2-glycoprotein I (beta2GPI) and prothrombin, and are known to interfere with phospholipid-dependent hemostatic pathways. In this study, we investigated whether purified aPL are able to interfere with inhibition of FXa by PZ/ZPI. beta2GPI modestly delayed the FXa inactivation by PZ/ZPI and most isolated aPL-IgGs were found to further increase the inhibitory potential of beta2GPI on PZ/ZPI activity. Without beta2GPI, the PZ/ZPI activity was unaffected by the addition of aPL-IgG. As PZ deficiency is hypothesized to lead to a prothrombotic state, we performed a case-control study to measure plasma levels of PZ and ZPI in 66 patients with autoimmune aPL and 152 normal controls. The prevalence of low PZ levels (below the 5th percentile of controls) was significantly greater in the 37 patients with definite antiphospholipid syndrome (APS) (24.3%) but not in the 29 aPL patients not fulfilling the criteria for APS (10.3%) compared with the normal group (4.6%, P < 0.001 vs. APS). ZPI antigen levels were similar in patients with aPL and normal controls. Concomitant PZ deficiency increased by approximately sevenfold the risk of arterial thrombosis in aPL patients. Taken together, these data suggest that the PZ/ZPI system is commonly impaired in aPL patients thus probably increasing the thrombotic risk.
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PMID:Autoimmune antiphospholipid antibodies impair the inhibition of activated factor X by protein Z/protein Z-dependent protease inhibitor. 1291 91

Unfertilized vertebrate eggs are arrested in metaphase of meiosis II with high cyclin B/Cdc2 activity to prevent parthenogenesis. Until fertilization, exit from metaphase is blocked by an activity called cytostatic factor (CSF), which stabilizes cyclin B by inhibiting the anaphase-promoting complex (APC) ubiquitin ligase. The APC inhibitor early mitotic inhibitor 1 (Emi1) was recently found to be required for maintenance of CSF arrest. We show here that exogenous Emi1 is unstable in CSF-arrested Xenopus eggs and is destroyed by the SCF(betaTrCP) ubiquitin ligase, suggesting that endogenous Emi1, an apparent 44-kDa protein, requires a stabilizing factor. However, anti-Emi1 antibodies crossreact with native Emi2/Erp1/FBXO43, a homolog of Emi1 and conserved APC inhibitor. Emi2 is stable in CSF-arrested eggs, is sufficient to prevent CSF release, and is rapidly degraded in a Polo-like kinase 1-dependent manner in response to calcium-mediated egg activation. These results identify Emi2 as a candidate CSF maintenance protein.
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PMID:A role for the anaphase-promoting complex inhibitor Emi2/XErp1, a homolog of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus eggs. 1575 81


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