The vitamin K-dependent blood coagulation factor IX as well as several extracellular regulatory proteins require vitamin K for the posttranslational synthesis of γ-carboxyglutamic acid, an amino acid clustered in the N-terminal Gla domain of these proteins [1,2]. The Gla domain is a membrane binding motif which, in the presence of calcium ions, interacts with phospholipid membranes that include phosphatidylserine.

The 3D structure of the Gla domain has been solved (see for example <PDB:1CFH>) [3,4]. Calcium ions induce conformational changes in the Gla domain and are necessary for the Gla domain to fold properly. A common structural feature of functional Gla domains is the clustering of N-terminal hydrophobic residues into a hydrophobic patch that mediates interaction with the cell surface membrane [4].

Proteins known to contain a Gla domain are listed below:

• A number of plasma proteins involved in blood coagulation. These proteins are prothrombin, coagulation factors VII, IX and X, proteins C, S, and Z.
• Two proteins that occur in calcified tissues: osteocalcin (also known as bone-Gla protein, BGP), and matrix Gla-protein (MGP).
• Proline-rich Gla proteins 1 and 2 [5].
• Cone snail venom peptides: conantokin-G and -T, and conotoxin GS [6].

The pattern we developed start with the conserved Gla-x(3)-Gla-x-Cys motif found in the middle of the domain which seems to be important for substrate recognition by the carboxylase [7] and end with the last conserved position of the domain (an aromatic residue). We also developed a profile that covers the whole Gla domain.