PIRSF000354

Coagulation factor V-like protein

PIRSF entry
Member databasePIRSF
PIRSF typefamily
Short nameFactors_V_VIII

Description

Mammalian coagulation factors V () and VIII () play analogous roles as non-enzymatic cofactors in the activation of prothrombin and factor X, respectively. They are proteolytically activated by thrombin and inactivated by activated protein C (APC); both require calcium ion for molecular stability
[2]
. The structure of APC-inactivated Factor Va has been determined
[3]
, revealing one high-affinity calcium ion-binding site and one copper ion-binding site. The domain architecture of the precursor molecules can be represented as A1-A2-B-A3-C1-C2. The A domains are diverged versions of the multicopper oxidase domain (). The B domain is highly variable and is removed during activation to yield non-covalently-associated heavy and light chains; this domain in mammalian factor V contains multiple copies of a 9-residue repeat (see ). The C domains () promote membrane binding.

The venom of certain Australian elapid snakes contains a prothrombin activator resembling mammalian plasma prothrombin activator. Its non-enzymatic subunit () shows approximately 50% identity to mammalian factor V and has a similar domain structure. However, the B domain is much shorter
[4]
. The venom protein of Pseudonaja textilis is 96% identical to its liver factor V but one critical cleavage site for APC is absent, rendering it resistant to inactivation and enhancing its potential toxicity. The two forms are encoded by separate genes that are expressed in a highly tissue-specific manner
[1]
.

References

1.Gene duplication of coagulation factor V and origin of venom prothrombin activator in Pseudonaja textilis snake. Minh Le TN, Reza MA, Swarup S, Kini RM. Thromb. Haemost. 93, 420-9, (2005). PMID: 15735790

2.Internal duplication and sequence homology in factors V and VIII. Fass DN, Hewick RM, Knutson GJ, Nesheim ME, Mann KG. Proc. Natl. Acad. Sci. U.S.A. 82, 1688-91, (1985). View articlePMID: 3920653

3.The crystal structure of activated protein C-inactivated bovine factor Va: Implications for cofactor function. Adams TE, Hockin MF, Mann KG, Everse SJ. Proc. Natl. Acad. Sci. U.S.A. 101, 8918-23, (2004). View articlePMID: 15184653

4.The nonenzymatic subunit of pseutarin C, a prothrombin activator from eastern brown snake (Pseudonaja textilis) venom, shows structural similarity to mammalian coagulation factor V. Rao VS, Swarup S, Kini RM. Blood 102, 1347-54, (2003). View articlePMID: 12730119

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