Vitamin K-dependent protein (VKD protein)

Vitamin K-dependent proteins are a diverse group of proteins that require enzymatic carboxylation of specific glutamate residues for full biological activity. This post-translational modification is catalyzed by gamma-glutamyl carboxylase, which uses reduced vitamin K as a cofactor. These proteins play critical roles in blood coagulation (including prothrombin, FVII, FIX, FX), bone metabolism (osteocalcin), regulation of vascular calcification (matrix Gla protein), and other physiological processes. Defects in carboxylation, as seen in vitamin K deficiency or upon treatment with warfarin and related anticoagulants, can lead to severe bleeding disorders, bone fragility, or ectopic calcification. The group is defined by the shared requirement for gamma-glutamyl carboxylase-catalyzed conversion of glutamic acid residues to gamma-carboxyglutamic acid (Gla), which imparts calcium-binding properties essential for protein function.

Other names

Vitamin K-dependent proteinsVKD proteinsGla domain-containing proteins

Warfarin and related drugs inhibit vitamin K epoxide reductase (VKORC1), thereby suppressing the regeneration of reduced vitamin K and, consequently, carboxylation of VKD proteins, resulting in impaired coagulation. Vitamin K supplementation restores reduced vitamin K, rescuing carboxylation activity.