Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the molecular basis of protein C deficiency in three families with a history of thromboembolic disease. An approximately 50% reduction in both functional and immunologic levels of protein C was detected in the plasma from two unrelated patients, designated protein C Osaka 1 and protein C Osaka 2. An approximately 50% reduction in functional level but normal immunologic level of protein C was detected in plasma from a third patient, designated protein C Osaka 3. DNA sequencing of the amplified DNA revealed one missense mutation in each case. Additional mutations in the coding sequence were excluded by DNA sequencing of all protein C exons. We identified a C-to-T change at nucleotide number 6,218 of the protein C gene in protein C Osaka 1. This results in the amino acid substitution of Arg-169 by Trp at the alpha-thrombin cleavage site. In protein C Osaka 2, a G-to-A change at nucleotide number 8,807 was identified leading to the amino acid substitution of Met-364 by Ile in the protease domain. This substitution may impair the synthesis or stability of protein C Osaka 2. In protein C Osaka 3, a G-to-C change at nucleotide number 8,868 was identified. This results in substitution of Gly-385 by Arg in the protease domain. Based on these, it was concluded that Arg-169-to-Trp mutation and Met-364-to-Ile mutation cause type I protein C deficiency and Gly-385-to-Arg mutation causes type II deficiency.
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PMID:Three missense mutations in the protein C heavy chain causing type I and type II protein C deficiency. 816 44

Previously, we observed a positive association of prothrombin concentrations with thrombin generation (fragment 1 + 2) and thrombin activity (fibrinopeptide A), but no association with protein C activation peptide levels. We further evaluated a potential beneficial effect of increased prothrombin concentrations on activated protein C generation by assessing the plasma concentration of activated protein C in complex with protein C inhibitor (APC-PCI). Blood samples were used from 195 family members of a large French-Canadian kindred with type I protein C deficiency due to a 3363C insertion in the protein C gene. We utilized a new and highly sensitive assay for measuring the concentration of APC-PCI complex as a measure of the level of activation of protein C. Means of the plasma concentrations of the APC-PCI complex were compared among carriers and non-carriers of the prothrombin G20210A mutation. Protein C activity levels were positively associated with APC-PCI complex plasma concentrations; however, APC-PCI complex levels were not different for carriers of the prothrombin G20210A mutation than for non-carriers. Thus, carriers of the prothrombin G20210A mutation do not have increased protein C activation despite the increased thrombin generation resulting from the higher prothrombin concentrations associated with the G20210A mutation.
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PMID:No effect of the prothrombin G20210A mutation on protein C activation in a large kindred with type I protein C deficiency. 1538 24