Vitamin K-dependent proteins (VKDPs) (VKDPs)

The Vitamin K-dependent proteins (VKDPs) are a group of proteins that require Vitamin K as a cofactor for their functional activation through post-translational gamma-carboxylation of glutamic acid residues. This group includes essential procoagulant factors (II, VII, IX, and X), as well as regulatory anticoagulant proteins (Protein C, Protein S, and Protein Z) and the signaling molecule Gas6 (UniProt: P00734, P08709, P00740, P00742). The resulting gamma-carboxyglutamic acid (Gla) residues enable these proteins to bind calcium ions, a step necessary for their attachment to negatively charged phospholipid surfaces during the coagulation cascade. Clinically, these proteins are the primary targets of Vitamin K antagonists like warfarin, which are widely used to prevent and treat thromboembolic conditions such as deep vein thrombosis and atrial fibrillation. Dysregulation of these factors can lead to severe hemostatic imbalances, manifesting as either life-threatening hemorrhage or pathological thrombosis. Beyond coagulation, members like Gas6 play significant roles in cell survival, proliferation, and the inflammatory response through interaction with TAM receptors (PMID: 22419547; StatPearls: Vitamin K, 2023).

Other names

Gla-domain containing proteinsVitamin K-dependent coagulation factorsVitamin K-dependent clotting factorsGamma-carboxyglutamic acid-containing proteins

Vitamin K antagonists (VKAs) inhibit the enzyme Vitamin K epoxide reductase (VKORC1), which is responsible for recycling oxidized Vitamin K back to its reduced form (Vitamin K hydroquinone). Reduced Vitamin K is an essential cofactor for the enzyme gamma-glutamyl carboxylase, which performs post-translational gamma-carboxylation of glutamic acid residues in the Gla-domain of these proteins. Without this modification, the proteins cannot bind calcium ions or associate with phospholipid membranes, rendering them biologically inactive and effectively inhibiting the coagulation cascade (StatPearls: Vitamin K, 2023; PMID: 22419547).