Gamma-carboxyglutamic acid domain (Gla domain) (Gla domain)

The Gamma-carboxyglutamic acid (Gla) domain is a specialized protein structural motif containing multiple gamma-carboxyglutamic acid residues, which are post-translationally modified from glutamic acid by the enzyme gamma-glutamyl carboxylase (Source: UniProt). This modification is strictly dependent on Vitamin K as a cofactor, making the Gla domain the functional centerpiece of the vitamin K cycle (Source: StatPearls). These domains are found in key blood coagulation factors such as Factors II, VII, IX, and X, where they facilitate calcium-dependent binding to negatively charged phospholipid membranes (Source: PubMed, PMID: 15660929). This membrane association is essential for the localized assembly of coagulation complexes at sites of vascular injury. Beyond hematology, Gla domains are present in Matrix Gla Protein (MGP), which inhibits vascular calcification, and Osteocalcin, which regulates bone mineralization (Source: NIH). Pharmacologically, the synthesis of functional Gla domains is inhibited by Vitamin K antagonists like warfarin to provide anticoagulation, while recombinant proteins containing these domains are used as replacement therapies for hemophilia and other bleeding disorders (Source: FDA).

Other names

Vitamin K-dependent Gla domainγ-carboxyglutamic acid domainGla-rich domainGamma-carboxyglutamate domain

Inhibition of post-translational gamma-carboxylation of glutamic acid residues by antagonizing vitamin K epoxide reductase (VKORC1), or direct replacement of functional carboxylated proteins in deficiency states.