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)

During the isolation and purification of erythroid cell-stimulating factors from fetal tissues and blood, we found that they were almost invariably contaminated with substances that inhibited thymidine incorporation into erythroid cells of fetal bovine liver. We have isolated and partially sequenced three of these inhibitory factors. The first one was a 46-kDa heparin-binding protein from fetal bovine serum with 80% sequence identity with human apolipoprotein H (apo H). Although human apo H had no inhibitory activity on thymidine incorporation, the bovine apo H-like protein inhibited thymidine incorporation with an ID50 of 36 nM. It probably belongs to a group of heparin-binding apolipoproteins such as apo B and E, which have been reported to inhibit hematopoietic cells. The second inhibitor isolated from fetal bovine serum was clearly cytotoxic at a concentration of 1 nM. This 11-kDa peptide seems to be structurally related to the anaphylatoxins. The third inhibitor was isolated from human fetal intestine. The amino-terminal sequence of this protein was nearly identical to the amino-terminal sequence of human phospholipase A2 isolated from pancreas or lung. Bovine liver erythroid cell membranes are particularly sensitive to phospholipases. Since the synthesis and secretion of phospholipase A2 has been reported to be under the control of interleukin-1 or tumor necrosis factor in different cells, it is possible that this enzyme may be secreted locally and play an important role in tissue remodeling during injury or fetal development.
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PMID:Isolation and characterization of three inhibitors of thymidine incorporation into bovine fetal liver cells. 206 6

Coagulation factors V and VIII are substrates for activated protein C. Binding sites for the protease have been localized to homologous sequences within the terminal A domains of these proteins. Since ceruloplasmin contains significant sequence homology to these domains, a study was undertaken to determine whether ceruloplasmin was an activated protein C-binding protein. Ceruloplasmin was observed to inhibit the activated protein C-catalyzed inactivation of both factor Va and factor VIII. Searches of the ceruloplasmin sequence revealed a decapeptide sequence, HAGMETTYTV (residues 1028-1037) that shares 60 and 40% sequence identity with the activated protein C binding sequence in factors VIII and V, respectively. This peptide also inhibited factor Va inactivation and in addition was observed to enhance the amidolytic activity of activated protein C. The ferrous oxidase activity of ceruloplasmin was stimulated 5-fold by activated protein C, and this effect was negated by the peptide HAGMETTYTV. These results indicate that these conserved sequences of ceruloplasmin and factors V and VIII interact with activated protein C and suggest that this region may be important in the regulation of this anticoagulant protein.
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PMID:Characterization of an interaction between protein C and ceruloplasmin. 210 10

We developed an ELISA to quantitate complexes of activated protein C (APC) with a major plasma APC inhibitor, alpha 1-antitrypsin (alpha 1AT) in human plasma based on the sandwich principle using two different antibodies directed towards protein C and alpha 1AT, respectively. This ELISA test was specific for APC:alpha 1AT complexes and sensitive to greater than or equal to 150 pg complex. Fifty-one of 56 healthy donors had APC:alpha 1AT complex levels above the detection limit (3 ng/ml) ranging from 4 to 14 ng/ml (mean value +/- SD: 7.6 +/- 2.5 ng/ml). Patients (n = 10) with disseminated intravascular coagulation (DIC) had detectable levels of APC:alpha 1AT complex ranging from 21 to 125 ng/ml (median: 69 ng/ml). Complexes of APC with plasma protein C inhibitor (PCI) were also measured using an ELISA sandwich assay. None of the 30 healthy donors had detectable levels (greater than or equal to 5 ng/ml) of APC:PCI complex, and plasma samples from 9 of 10 DIC patients had detectable concentrations of APC:PCI complex ranging from 10 to 63 ng/ml (median: 22 ng/ml). APC:alpha 1AT complex was detected in 25 of 26 patients with deep venous thrombosis (DVT), with levels ranging from 5 to 136 ng/ml (median: 23 ng/ml), whereas APC:PCI was detected in only 6 DVT patients, with levels between 11 and 105 ng/ml. PCI antigen levels in 70 normals ranged from 56 to 175% (mean +/- SD: 99.1% +/- 24.2%). PCI antigen levels were decreased in DIC patients, in patients with cerebral arterial thrombosis, and in DVT patients undergoing heparin therapy, but not in patients with myocardial infarction. PCI antigen levels were decreased much further in DVT patients receiving heparin compared to those not receiving heparin, showing that heparin therapy is associated with a decrease in PCI levels. The detection in normal subjects and in thrombotic patients of circulating APC:inhibitor complexes supports the view that the protein C pathway is activated during DIC and DVT. Moreover, it emphasizes that both PCI and alpha 1AT are physiologic inhibitors of APC. Thus, measurement of APC complexes may provide sensitive parameters for specific detection of activation of the clotting and protein C pathways.
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PMID:Determination of plasma protein C inhibitor and of two activated protein C-inhibitor complexes in normals and in patients with intravascular coagulation and thrombotic disease. 217 67

By use of six highly purified exoglycosidases with well-defined specificity, the oligosaccharide units of human plasma beta 2-glycoprotein I (beta 2I) were modified by sequential enzymatic degradation. The released monosaccharides (NeuAc, Gal, GlcNAc, and Man) were quantified, and the carbohydrate compositions of the resulting glycoprotein (gp) derivatives were determined. The gp was found to be both partially sialylated and galactosylated. These findings which are in agreement with earlier reports suggest that the carbohydrate moiety of beta 2I possesses more bi- than tri-antennas, probably three of the former and two of the latter carbohydrate units. Circular dichroic (CD) spectra of native beta 2I and its derivatives were measured in aqueous buffer and 2-chloroethanol (2-CE). Analysis of these spectra for elements of secondary structure showed beta 2I and most of the derivatives to contain predominantly beta-sheet and beta-turn structures. The lack of alpha-helical structures in aqueous buffer was noted. Removal of a large portion of the carbohydrate moiety did not alter the CD spectra or secondary structure of beta 2I in either aqueous buffer or in 2-CE. However, after enzymatic removal of approximately 96% of the carbohydrate moiety, large significant changes in the spectra and secondary structures were observed. In aqueous buffer a shift in the wavelength minimum occurred, accompanied by an increase in the magnitude of the molar ellipticity and the amount of beta-turn, with a reduction in random coil. One-third of the amino acids which were originally in random coil conformation assumed beta-turns after removal of 96% of the carbohydrate moiety.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the carbohydrate moiety on the secondary structure of beta 2-glycoprotein. I. Implications for the biosynthesis and folding of glycoproteins. 220 70

An 8 kd heparin-binding peptide which stimulates thymidine incorporation in cultures of fetal calf liver erythroid cells was isolated from fetal bovine serum by affinity chromatography on Heparin-Sepharose, ion exchange chromatography, gel filtration and reversed-phase HPLC. The N-terminal sequence of the isolated peptide was identical to the N-terminal sequence of bovine erythrotropin or insulin-like growth factor II (IGF II). The potential heparin-binding site of IGF II is probably situated in the arginine-rich C-peptide region. The affinities of human recombinant IGF I and II were compared with those of apolipoprotein H (a plasma heparin-binding protein) and bovine insulin in a heparin-affinity column. The retention times were in the order: Apolipoprotein H greater than hrIGF II greater than hrIGF I greater than insulin (no retention). This unusual property of IGF II suggests that it may be captured in the extracellular matrix in a similar way to fibroblast growth factor, interleukin 3 or granulocyte/macrophage colony-stimulating factor.
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PMID:A heparin-binding erythroid cell stimulating factor from fetal bovine serum has the N-terminal sequence of insulin-like growth factor II. 230 23

A 46 kDa heparin-binding protein which inhibits thymidine incorporation in cultures of fetal calf liver erythroid cells was isolated from fetal bovine serum by affinity chromatography on heparin-Sepharose, ion-exchange chromatography, gel filtration and reversed-phase h.p.l.c. The N-terminal sequence of the first 22 amino acids showed 81% identity with the published sequence of human apolipoprotein H. The isolated protein inhibited thymidine incorporation with an ED50 (concn. producing 50% of maximal effect) of 36 nM. A 100% inhibition of thymidine incorporation and a 40% decrease in cell numbers in cultures of fetal calf erythroid cells were observed at a protein concentration of 840 nM. No effects could be seen in cultures of 3T3 cells used as controls. Human apolipoprotein H had no inhibitory activity in any of the cell cultures tested, suggesting a species-specificity or a different structure or function for the bovine heparin-binding protein.
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PMID:Isolation from fetal bovine serum of an apolipoprotein-H-like protein which inhibits thymidine incorporation in fetal calf erythroid cells. 232 84

Anti-phospholipid (aPL) antibodies that exhibit binding in cardiolipin (CL) ELISA can be purified to greater than 95% purity by sequential phospholipid affinity and ion-exchange chromatography. However, these highly purified aPL antibodies do not bind to the CL antigen when assayed by a modified CL ELISA in which the blocking agent does not contain bovine serum, nor do they bind to phospholipid affinity columns. Binding to the phospholipid antigen will only occur if normal human plasma, human serum, or bovine serum is present, suggesting that the binding of aPL antibodies to CL requires the presence of a plasma/serum cofactor. Using sequential phospholipid affinity, gel-filtration, and ion-exchange chromatography, we have purified this cofactor to homogeneity and shown that the binding of aPL antibodies to CL requires the presence of this cofactor in a dose-dependent manner. N-terminal region sequence analysis of the molecule has identified the cofactor as beta 2-glycoprotein I (beta 2GPI) (apolipoprotein H), a plasma protein known to bind to anionic phospholipids. These findings indicate that the presence of beta 2GPI is an absolute requirement for antibody-phospholipid interaction, suggesting that bound beta 2GPI forms the antigen to which aPL antibodies are directed. Recent evidence indicates that beta 2GPI exerts multiple inhibitory effects on the coagulation pathway and platelet aggregation. Interference with the function of beta 2GPI by aPL antibodies could explain the thrombotic diathesis seen in association with these antibodies.
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PMID:Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). 234 21

A study was made of the level of alpha- and beta-lipoproteins, apolipoprotein H and tissue protein alpha 2-glycoprotein of the arteriosclerotically changed aortic wall in the blood serum of 129 patients with coronary arteriosclerosis, 50 patients with various diseases of the internal organs without clinical signs of arteriosclerosis and in 26 healthy patients by the immunodiffusion method using standard assays. A significant increase in beta- and alpha-lipoprotein indices was revealed in the groups of patients with coronary heart disease as compared to the healthy persons. alpha 2-glycoprotein of the arteriosclerotically changed aortic wall was undetectable in the blood serum of the healthy persons; in the group of patients without clinical signs of coronary heart disease this protein was detected in 5 patients only in the concentration of 4-8 micrograms/ml. alpha 2-glycoprotein concentration in the blood serum of the patients with the ischemic, thrombonecrotic and fibrous stages of arteriosclerosis was much higher (23.5 +/- 1.0; 27.5 +/- 2.9 and 35.3 +/- 2.2 micrograms/ml respectively). The proposed immunochemical determination of some indices of the blood serum can be of use to assess the activity of arteriosclerotic processes in patients with coronary heart disease. The determination of the level of alpha 2-glycoprotein of the arteriosclerotically changed aortic wall serves this purpose most adequately.
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PMID:[Immunochemical study of the alpha 2-glycoprotein from the atherosclerotically altered aortic wall in the blood serum of ischemic heart disease patients]. 241 47

cDNAs encoding the complement decay-accelerating factor (DAF) were isolated from HeLa and differentiated HL-60 lambda gt cDNA libraries by screening with a codon preference oligonucleotide corresponding to DAF NH2-terminal amino acids 3-14. The composite cDNA sequence showed a 347-amino acid protein preceded by an NH2-terminal leader peptide sequence. The translated sequence beginning at the DAF NH2 terminus encodes four contiguous approximately equal to 61-amino acid long repetitive units of internal homology. The repetitive regions contain four conserved cysteines, one proline, one glycine, one glycine/alanine, four leucines/isoleucines/valines, one serine, three tyrosines/phenylalanines, and one tryptophan and show striking homology to similar regions previously identified in factor B, C2, C4 binding protein, factor H, C1r, factor XIII, interleukin 2 receptor, and serum beta 2-glycoprotein I. The consensus repeats are attached to a 70-amino acid long segment rich in serine and threonine (potential O-glycosylation sites), which is in turn followed by a stretch of hydrophobic amino acids. RNA blot analysis of HeLa and HL-60 RNA revealed three DAF mRNA species of 3.1, 2.7, and 2.0 kilobases. The results indicate that portions of the DAF gene may have evolved from a DNA element common to the above proteins, that DAF cDNA predicts a COOH-terminal anchoring polypeptide, and that distinct species of DAF message are elaborated in cells.
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PMID:Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement. 243 22

Amino acid sequence data derived from tryptic peptides of the decay accelerating factor indicate that this complement regulatory protein contains a sequence with homology to the superfamily of structurally related complement proteins, including the C4 binding protein, factor H, complement receptor type 1, complement receptor type 2, Ba, C1r, and to their non-complement relatives, including beta 2-glycoprotein I, factor XIIIb, the alpha 1 chain of haptoglobin, and the interleukin 2 receptor. Identifying DAF as a member of the superfamily of structurally related complement proteins provides evidence that DAF may contain a functionally important C4b and C3b binding domain.
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PMID:Decay accelerating factor (DAF) peptide sequences share homology with a consensus sequence found in the superfamily of structurally related complement proteins and other proteins including haptoglobin, factor XIII, beta 2-glycoprotein I, and the IL-2 receptor. 243 13


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