Coagulation factor-like, Gla domain superfamily
IPR017857
Definition
This superfamily represents the Gla domain found in a subset of coagulation factors (VII, IX and X), related blood regulators (such as vitamin K), and gla-containing proteins. Venom prothrombin activator D found in snakes, also represented in this entry, is functionally similar to blood coagulation factor Xa PMID:10397729. This entry also includes the hormone insulin-like peptide protein 05. In the mice's gut, it could play a role in promoting hepatic glucose production during periods of energy deprivation PMID:2706986. The GLA (gamma-carboxyglutamic acid-rich) domain contains glutamate residues that have been post-translationally modified by vitamin K-dependent carboxylation to form gamma-carboxyglutamate (Gla) [[cite:PMID:18374189], [cite:PMID:11818531], [cite:PMID:18374194]]. All glutamic acid (Glu) residues present in the GLA domain are potential carboxylation sites; in coagulation proteins, all Gu residues are modified to Gla, while in osteocalcin and matrix Gla proteins only some Glu residues are modified to Gla. The GLA domain is responsible for the high-affinity binding of calcium ions. It starts at the N-terminal extremity of the mature form of proteins and ends with a conserved aromatic residue; a conserved Gla-x(3)-Gla-x-Cys motif PMID:3317405 is found in the middle of the domain, which seems to be important for substrate recognition by the carboxylase. The 3D structure of the GLA domain has been solved [[cite:PMID:7713897], [cite:PMID:8663165]]. Calcium ions induce conformational changes in the GLA domain that are necessary for the proper folding of the GLA domain. 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 PMID:8663165.
11 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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