Disease relevance of LOC407212

• Staphylocoagulase (SC) is a protein secreted by the human pathogen, Staphylococcus aureus, that activates human prothrombin (ProT) by inducing a conformational change [1].
• To characterize the gene more thoroughly, two bovine genomic phage libraries were screened by using prothrombin cDNAs as hybridization probes [2].
• We have studied PT synthesis by Reuber H-35 rat hepatoma cells exposed to vitamin K and [3H]leucine in serum-free cultures [3].
• Mechanism and effects of the binding of lupus anticoagulant IgG and prothrombin to surface phospholipid [4].
• These data may have implications for understanding the mechanisms of the abnormalities in serum prothrombin times reported in Bernard-Soulier syndrome, hemorrhage in von Willebrand disease (vWD), and the increased risk of thrombosis associated with elevated vWF levels [5].

Psychiatry related information on LOC407212

• To determine whether cleavage was necessary for function, prothrombin conversion reaction mixtures were monitored for thrombin formation and Factor Va cleavage with time in a defined phospholipid vesicle model system [6].

High impact information on LOC407212

• Vitamin K, prothrombin and gamma-carboxyglutamic acid [7].
• Thrombin and the combination of prothrombin plus prothrombinase induced proteoglycan release from both normal and arthritic cartilages [8].
• Treatment of cultured endothelial cells with 0.5-10 mM homocysteine had no effect on cell morphology, but did increase Factor V activity and prothrombin activation by Factor Xa [9].
• These studies demonstrate that freshly obtained vessels with a continuous layer of native endothelium can support activation of Factor X and prothrombin: vessel-bound Factor IXa can activate Factor X in the presence of VWF/Factor VIII [10].
• The apparent efficiency of prothrombin activation, however, is dampened by the presence of functional antithrombin III on the vessel wall [10].

Chemical compound and disease context of LOC407212

• Quantification of the total virion and DB phospholipid, and comparison of prothrombin conversion rates to experiments conducted using known concentrations of PS-containing vesicles showed that 8.5% and 7.2% of the CMV and DB phospholipid, respectively is procoagulant [11].
• This response has now been studied in rat hepatoma (H-35) cells in which prothrombin secretion is decreased 90% by incubation in the presence of warfarin [12].
• In a previous study, we prepared a monoclonal antibody (MoAb) to coagulation factor IX (FIX), designated 65-10, which interfered with the activation of FIX by the activated factor XI/Ca(2+) and neutralized the prolonged ox brain prothrombin time of hemophilia B(M) [11,12] [13].
• The apparent Km value toward prothrombin was relatively low (2.3 microM), suggesting that tryptase contributes to blood coagulation or the process of fibrosis in tissues [14].
• The 65-10 MoAb antibody neutralized the prolonged ox brain prothrombin time of hemophilia B(M) Nagoya 2 ((180)Arg -->Trp) and Kashihara ((181)Val --> Phe) as well as B(M) Kiryu ((313)Val --> Asp) and Niigata ((390)Ala --> Val) [13].

Biological context of LOC407212

• SC-bound ProT efficiently clots fibrinogen, thus bypassing the physiological blood coagulation pathway [1].
• These results suggest that the catalytic site in the SC-(1-325).bovine ProT complex is incompletely formed [1].
• Comparison of human and bovine fibrinogen as substrates of human and bovine thrombin and the SC-(1-325).(pro)thrombin complexes indicates that the species specificity of SC-(1-325) cofactor activity is determined primarily by differences in conformational activation of bound ProT [1].
• These analyses suggested that the bovine genome contains a single prothrombin gene that is at least 10 kilobase pairs (kbp) in size [2].
• Heteroduplex analysis of the cloned genomic DNA and cDNA showed that the prothrombin gene is 14.9 kbp in size and contains at least 14 exons interrupted by 13 introns [2].

Anatomical context of LOC407212

• The activation of prothrombin by vessel-bound Factor Xa was inhibited by anti-bovine Factor V IgG, suggesting that there is interaction of Factor Xa with a Factor V-like molecule provided by the endothelial cell surface [10].
• Exogenous phospholipid and Factor V were not required for Factor X and prothrombin activation on the intact native endothelium [10].
• In contrast, nonvascular cells (human foreskin fibroblasts, bovine corneal endothelial cells, or human fetal lung cells) had either no or very little effect on prothrombin activation [15].
• This enriched mRNA was 50% prothrombin mRNA, as determined by a reticulocyte lysate translation assay [16].
• Poly(A)-RNA enriched for prothrombin was isolated by specific immunoprecipitation of bovine liver polysomes [16].

Associations of LOC407212 with chemical compounds

• The bovine plasma zymogen prothrombin contains a number of gamma-carboxyglutamic acid residues which are not found in an abnormal prothrombin produced when cattle are given the vitamin K antagonist dicoumarol [17].
• Hydrolysis of the purified radioactive prothrombin resulted in a loss of 50% of the radioactivity and subsequent chromatography of the amino acid hydrolyzate demonstrated that the remaining radioactivity was entirely in glutamic acid [17].
• Most of the radioactive protein which can be obtained from the microsomal pellet by extraction with 0.25% Triton X-100 has been identified as prothrombin and it can be shown that all of the radioactivity is in the amino-terminal activation fragment of prothrombin [17].
• Abnormal, biologically inactive forms of prothrombin have previously been shown to appear in the plasma of cows or humans given coumarin anticoagulants [18].
• This arginine residue is absolutely conserved in the catalytic domain of normal human and bovine factor IX, X and prothrombin [19].

Regulatory relationships of LOC407212

• These data suggest that prothrombin fragment 2 may be an important factor in controlling the localization of clot formation by regulating the interaction between thrombin and antithrombin III [20].
• Blood plasma obtained from the umbilical vein and artery had a longer prothrombin time but shorter activated partial thromboplastin time and lower concentrations of fibrinogen and plasminogen than peripheral blood plasma [21].

Other interactions of LOC407212

• Plasma abnormal prothrombin and microsomal prothrombin precursor in various species (38492) [18].
• Deriving the generic structure of the fibronectin type II domain from the prothrombin Kringle 1 crystal structure [22].
• The Ba fragment was found to contain three regions of internal sequence homology which were unrelated to the "kringle" regions of prothrombin and plasminogen and which suggest an independent evolution for the B genome [23].
• The gamma-carboxyglutamic acid and epidermal growth factor-like domains of factor X. Effect of isolated domains on prothrombin activation and endothelial cell binding of factor X [24].
• An abnormal blood coagulation factor IX has been isolated from the blood of a hemophilia B patient with a variant of the disease (hemophilia Bm) characterized by a normal concentration of factor IX antigen, negligible factor IX coagulant activity, and a prolonged prothrombin time with bovine tissue factor [25].

Analytical, diagnostic and therapeutic context of LOC407212

• The bovine prothrombin gene was characterized by Southern blot analysis of bovine genomic DNA using bovine prothrombin cDNA fragments as hybridization probes [2].
• We determined by X-ray crystallography and NMR spectroscopy the lysophosphatidylserine-binding site in the bovine prothrombin Gla domain [26].
• Under-gamma-carboxylated prothrombin is also secreted from warfarin-treated human (HepG2) cell cultures but is degraded in the endoplasmic reticulum in warfarin-treated rat (H-35) cell cultures [27].
• Magnesium and calcium ion binding to bovine prothrombin fragment 1. A circular dichroism, fluorescence, and 43Ca2+ and 25Mg2+ nuclear magnetic resonance study [28].
• The prothrombin activator from the venom of Oxyuranus scutellatus (Taipan snake) was purified by gel filtration on Sephadex G-200 and ion-exchange chromatography on QAE-Sephadex [29].

References