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Haemostasis 1986Using recombinant DNA techniques, DNA fragments coding for bovine prothrombin mRNA have been cloned and characterized. Structural studies have revealed that prothrombin... (Review)
Review
Using recombinant DNA techniques, DNA fragments coding for bovine prothrombin mRNA have been cloned and characterized. Structural studies have revealed that prothrombin mRNA encodes a precursor protein having an amino-terminal extension of 43 amino acid residues. Using bovine prothrombin cDNA as a hybridization probe, the genes coding for human and bovine prothrombin have been isolated and partially characterized. The organization of the prothrombin gene is similar, but not identical to the organization of the genes coding for the other vitamin-K-dependent clotting factors.
Topics: Amino Acid Sequence; Animals; Biological Evolution; Cattle; DNA; DNA, Recombinant; Genes; Humans; Protein Conformation; Prothrombin; RNA, Messenger
PubMed: 3530900
DOI: 10.1159/000215295 -
Critical Reviews in Eukaryotic Gene... 1998Prothrombin and thrombin are involved in diverse biological functions. The structure of prothrombin has been studied extensively and its cDNA has been cloned from... (Review)
Review
Prothrombin and thrombin are involved in diverse biological functions. The structure of prothrombin has been studied extensively and its cDNA has been cloned from several species. The tissue-specific expression of this protein has been studied, as well as the developmental expression pattern. The structure of the human gene coding for prothrombin has been determined, and gene regulation studies have been performed that indicate that HNF-1 might be responsible for the liver-specific expression of this protein. Other regulatory elements have been identified. In order to further study the biological properties of prothrombin, prothrombin-deficient mice have been generated using gene targeting technology. Prothrombin deficiency in mice results in partial embryonic lethality. The mice that survive to birth die from bleeding events. The embryonic lethality occurs between embryonic days 9.5 and 11.5 and appears to be due to the loss of integrity of the vasculature due to a failure in blood coagulation. These results indicate that prothrombin plays not only a key role in hemostasis but suggests that it may be important for mouse development.
Topics: Amino Acid Sequence; Animals; Base Sequence; Blood Coagulation; DNA; Fibrinolysis; Gene Expression Regulation, Developmental; Homozygote; Humans; Molecular Sequence Data; Protein Conformation; Prothrombin; Regulatory Sequences, Nucleic Acid
PubMed: 9714898
DOI: 10.1615/critreveukargeneexpr.v8.i2.60 -
Chemical Immunology 2000
Review
Topics: Amino Acid Sequence; Antibodies, Catalytic; Autoantibodies; Binding Sites; Humans; Immunoglobulin Light Chains; In Vitro Techniques; Lupus Erythematosus, Systemic; Molecular Sequence Data; Prothrombin; Thromboplastin
PubMed: 11706702
DOI: 10.1159/000058801 -
Expert Review of Proteomics Dec 2014The structure of prothrombin has eluded investigators for decades but recent efforts have succeeded in revealing the architecture of this important clotting factor....
The structure of prothrombin has eluded investigators for decades but recent efforts have succeeded in revealing the architecture of this important clotting factor. Unanticipated features have emerged outlining the significant flexibility of the zymogen due to linker regions connecting the γ carboxyglutamic domain, kringles and protease domain. A new, structure-based framework helps in defining a molecular mechanism of prothrombin activation, rationalizes the severe bleeding phenotypes of several naturally occurring mutations and identifies targets for drug design.
Topics: Humans; Mutation; Protein Structure, Tertiary; Prothrombin
PubMed: 25327788
DOI: 10.1586/14789450.2014.971763 -
Blood May 2024
Topics: Humans; Prothrombin
PubMed: 38722662
DOI: 10.1182/blood.2024024240 -
The Journal of Biological Chemistry Dec 1975Human prothrombin has been purified from American Red Cross Factor IX concentrates. Studies of the activation of the human prothrombin with the use of sodium dodecyl... (Comparative Study)
Comparative Study
Human prothrombin has been purified from American Red Cross Factor IX concentrates. Studies of the activation of the human prothrombin with the use of sodium dodecyl sulfate electrophoretic analysis of activation products indicated that human prothrombin activation is similar to bovine prothrombin activation. Molecular weight analysis of human prothrombin and intermediated by sodium dodecyl sulfate co-electrophoresis with bovine prothrombin and its intermediates resulted in molecular weights of 70,000 for prothrombin, 51,000 for intermediate 1, 41,000 for intermediate 2, 23,000 for intermediate 3, and 13,000 for intermediate 4. Amino acid compositions of human prothrombin and intermediates are similar to those for bovine prothrombin and intermediates. NH2-terminal sequence studies of human prothrombin, intermediates, and alpha-thrombin A and B chains placed the intermediates in the parent human prothrombin molecule as described for the bovine system. Intermediate 3 is the NH2-terminal of prothrombin, and intermediate 1 is the COOH-terminal segment of the zymogen. Intermediate 4 is the NH2-terminal of intermediate 1. Intermediate 2', the immediate precursor of alpha-thrombin, is the COOH-terminal segment of intermediate 1. In general, a high degree of homology in the primary structure of prothrombin and intermediates was observed between the human and bovine system. The NH2-terminal sequences of human intermediate 2' and alpha-thrombin A chain are identical. However, human intermediate 2' isolated in a manner identical with that used for the isolation of bovine intermediate 2 is homologous with bovine intermediate 2, beginning with residue 14.
Topics: Amino Acid Sequence; Amino Acids; Animals; Cattle; Chromatography, Affinity; Enzyme Activation; Factor IX; Humans; Macromolecular Substances; Molecular Weight; Prothrombin
PubMed: 1238394
DOI: No ID Found -
Current Drug Targets. Cardiovascular &... Dec 2004Activation of prothrombin to mature thrombin in vivo occurs by the proteolytic action of the prothrombinase complex consisting of serine proteinase factor Xa, and... (Review)
Review
Activation of prothrombin to mature thrombin in vivo occurs by the proteolytic action of the prothrombinase complex consisting of serine proteinase factor Xa, and cofactors that include factor Va, Ca(2+) ions and phospholipids. Several exogenous prothrombin activators are found in snake venom. Among these, Group C prothrombin activators resemble the factor Xa-factor Va complex, while Group D activators are structurally and functionally similar to factor Xa. This review provides a detailed description of current knowledge on Group D prothrombin activators and highlights the importance of studying this family of proteins in enhancing our understanding of structure-function relationships in the mammalian prothrombinase complex.
Topics: Animals; Anticoagulants; Enzyme Activation; Factor V; Factor Xa; Humans; Protein Conformation; Prothrombin; Snake Venoms; Structure-Activity Relationship
PubMed: 15578960
DOI: 10.2174/1568006043335781 -
Human Pathology Jul 1974
Topics: Animals; Blood Coagulation; Blood Coagulation Factors; Cattle; Chemical Phenomena; Chemistry; Dogs; Horses; Humans; Molecular Weight; Prothrombin
PubMed: 4857813
DOI: 10.1016/s0046-8177(74)80017-1 -
Archives of Internal Medicine Sep 1977A hemophilliac with a factor VIII inhibitor was bleeding massively from an extensive surgical wound. After ten days of unsuccessful management by conservative measures,...
A hemophilliac with a factor VIII inhibitor was bleeding massively from an extensive surgical wound. After ten days of unsuccessful management by conservative measures, he was given a single infusion of prothrombin complex concentrate (Konyne). Bleeding stopped immediately and the wound healed without further recurrence of bleeding. Although the activated partial thromboplastin time shortened following the infusion, the exact physiologic mechanism whereby these concentrates bypass the need for factor VIII clotting activity is unknown.
Topics: Adult; Hemophilia A; Hemorrhage; Humans; Male; Postoperative Complications; Prothrombin
PubMed: 901090
DOI: No ID Found -
Hepatology (Baltimore, Md.) Oct 1993Des-gamma-carboxyprothrombin (DCP) appears to be a useful tumor marker for the evaluation of patients with HCC. DCP is produced by the malignant hepatocyte and appears... (Review)
Review
Des-gamma-carboxyprothrombin (DCP) appears to be a useful tumor marker for the evaluation of patients with HCC. DCP is produced by the malignant hepatocyte and appears to result from an acquired posttranslational defect in the vitamin K-dependent carboxylase system. DCP production is independent of vitamin K deficiency, although pharmacological doses of vitamin K can transiently suppress DCP production in some tumors. DCP levels greater than 0.1 AU/ml (100 ng/ml) on ELISA are highly suggestive of HCC or tumor recurrence. Normalization of DCP levels correlates well with successful tumor resection and appears to be an excellent marker of tumor activity. Plasma DCP does not correlate with AFP levels. However, when used together, DCP and AFP assays increase the sensitivity to HCC in more than 85% of patients. The specificity of the DCP assay appears to be superior to that of AFP; fewer than 5% of patients with nonmalignant liver disorders have DCP levels in excess of 100 ng/ml. In patients with medium to large HCC, DCP levels do correlate with tumor size. In tumors of less than 3 cm, DCP levels are increased in only 20% of patients. However, the diagnostic threshold for the DCP assay may be improved by newer assays that can detect partially carboxylated DCP species not measured by the monoclonal antibody-based ELISA.
Topics: Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Protein Precursors; Prothrombin; Vitamin K
PubMed: 8406374
DOI: 10.1002/hep.1840180434