Two parallel prothrombin activator systems in Australian rough-scaled snake, Tropidechis carinatus

SummaryIt is uncommon for similar pathways/systems to be involved in highly divergent functions within single organisms. Earlier, we have shown that trocarin D, a venom prothrombin activator, from the Australian rough-scaled snake Tropidechis carinatus, is structurally and functionally similar to the blood coagulation factor Xa (FXa). The presence of a haemostatic system in these snakes implies that they have two parallel prothrombin activating systems: one in the plasma, that participates in the life saving process of blood clotting and the other in their venom, where it acts as a toxin. Here, we report the complete cDNA sequence encoding the blood coagulation factor X (FX) from the liver of T. carinatus. Deduced T. carinatus FX sequence shows ~80% identity with trocarin D but ~50% identity with the mammalian FX. Our present study confirms the presence of two separate genes – one each for FX and trocarin D, that code for similar proteins in T. carinatus snake. These two genes have different expression sites and divergent uses suggesting that snake venom prothrombin activators have probably evolved by the duplication of the liver FX gene and subsequently marked for tissue-specific expression in the venom gland.

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Identification of a Binding Site For Blood Coagulation Factor Xa on the Heavy Chain of Factor Va. Amino Acid Residues 323−331 of Factor V Represent an Interactive Site for Activated Factor X†,‡

Biochemistry ◽

10.1021/bi026208+ ◽

2002 ◽

Vol 41 (42) ◽

pp. 12715-12728 ◽

Cited By ~ 13

Author(s):

Michael Kalafatis ◽

Daniel O. Beck

Keyword(s):

Amino Acid ◽

Binding Site ◽

Blood Coagulation ◽

Heavy Chain ◽

Factor Xa ◽

Coagulation Factor ◽

Factor V ◽

Amino Acid Residues ◽

Factor X ◽

Factor Va

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The recruitment of blood coagulation factor X into snake venom gland as a toxin

Thrombosis and Haemostasis ◽

10.1160/th09-03-0162 ◽

2009 ◽

Vol 102 (09) ◽

pp. 469-478 ◽

Cited By ~ 11

Author(s):

Shiyang Kwong ◽

Anthony E. Woods ◽

Peter J. Mirtschin ◽

Ruowen Ge ◽

R. Kini

Keyword(s):

Blood Coagulation ◽

Snake Venom ◽

Coagulation Factor ◽

Venom Gland ◽

Inducible Expression ◽

Luciferase Expression ◽

Factor X ◽

Cis Elements ◽

Mammalian Cell Lines ◽

Intron 1

SummaryTrocarin D is a prothrombin activator from the Tropidechis carinatus venom. It is a functional and structural homologue to mammalian blood coagulation factor Xa.Trocarin D is hypothesised to have evolved from its factor X counterpart (TrFX) through gene duplication and recruitment.The genes of trocarin D and TrFX have significant sequence identities, except for insertions/deletions in their intron 1 and promoter regions. In trocarin D intron 1 region, there are three insertions and two deletions. In trocarin D promoter region, there is a novel 264 bp insertion which has potential cis-elements.This insertion is termed as Venom Recruitment/Switch Element (VERSE) and is hypothesised to account for switching the low-level constitutive expression of factor X in the liver to the high-level inducible expression of trocarin D in the venom gland. To understand the role of VERSE in the trocarin D expression,its cis-elements were characterised by luciferase assays in mammalian cell lines as well as snake venom gland cells. The ability of VERSE to drive luciferase expression is comparable to that of the trocarin D promoter. The predicted cis-elements are important in promoting expression as their mutagenesis resulted in lower luciferase expression.VERSE minimal core promoter and three novel cis-elements (two up-regulatory and one suppressor elements) were identified using deletion/site-directed mutagenesis studies. VERSE is primarily responsible for the increase of trocarin D expression. The insertions/deletions within trocarin D intron 1 need to be characterised for their role in tissue-specific and inducible expression of trocarin D.

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Liver-specific expression of the gene coding for human factor X, a blood coagulation factor.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)42530-6 ◽

1992 ◽

Vol 267 (11) ◽

pp. 7395-7401

Author(s):

C.H. Miao ◽

S.P. Leytus ◽

D.W. Chung ◽

E.W. Davie

Keyword(s):

Blood Coagulation ◽

Human Factor ◽

Coagulation Factor ◽

Factor X ◽

Specific Expression ◽

Gene Coding

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Activation of Human Coagulation Factor VIII by Activated Factor X, the Common Product of the Intrinsic and the Extrinsic Pathway of Blood Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657137 ◽

1982 ◽

Vol 47 (02) ◽

pp. 096-100 ◽

Cited By ~ 22

Author(s):

K Mertens ◽

R M Bertina

Keyword(s):

Factor Viii ◽

Human Factor ◽

Intrinsic Factor ◽

Factor Xa ◽

Coagulation Factor ◽

Factor X ◽

Extrinsic Factor ◽

Extrinsic Pathway ◽

Factor Ixa ◽

The Common

SummaryThe intrinsic activation of human factor X has been studied in a system consisting of purified factors and in plasma. In both these systems factor Xa stimulated the activation of factor X by factor IXa plus factor VIII This is due to the activation of factor VIII by factor Xa. When this factor Xa is formed via the extrinsic pathway, the extrinsic factor X activator functions as a stimulator of the intrinsic factor X activator.

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