Gene duplication of coagulation factor V and origin of venom prothrombin activator in Pseudonaja textilis snake

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

21 Scopus Citations
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Author(s)

Detail(s)

Original languageEnglish
Pages (from-to)420-429
Journal / PublicationThrombosis and Haemostasis
Volume93
Issue number3
Publication statusPublished - Mar 2005
Externally publishedYes

Abstract

The origin and evolution of venom toxins is a mystery that has evoked much interest. We have recently shown that pseutarin C, a prothrombin activator from Pseudonaja textilis venom, is structurally and functionally similar to mammalian coagulation factor Xa - factor Va complex. Its catalytic subunit is homologous to factor Xa while the nonenzymatic subunit is homologous to factorVa. P. textilis therefore has two parallel prothrombin activator systems: one expressed in its venom gland as a toxin and the other expressed in its liver and released into its plasma as a haemostatic factor. Here we report the complete amino acid sequence of factorV (FV) from its liver determined by cDNA cloning and sequencing. The liver FV shows 96% identity to pseutarin C nonenzymatic subunit. Most of the functional sites involved in its interaction with factor Xa and prothrombin are conserved. However, many potential sites of post-translational modifications and one critical cleavage site for activated protein C are different. The absence of the latter cleavage site makes pseutarin C nonenzymatic subunit resistant to inactivation and enhances its potential as an excellent toxin. By PCR and real-time quantitative analysis, we show that pseutarin C nonenzymatic subunit gene is expressed specifically in the venom gland at ∼280 fold higher than that of FV gene in liver. These two are thus encoded by two separate genes that express in a highly tissue-specific manner. Our results imply that the gene encoding pseutarin C nonenzymatic subunit was derived by the duplication of plasma FV gene and they have evolved to perform distinct functions. © 2005 Schattauer GmbH, Stuttgart.

Research Area(s)

  • Coagulation factor V, Gene duplication, Pseudonaja textilis, Venom toxin evolution