-
Overview
-
Pathways & interactions
-
Cross-references
Gamma-carboxyglutamic acid-rich (GLA) domain superfamily (IPR035972)
Short name: GLA-like_dom_SF
Overlapping entries
- Gamma-carboxyglutamic acid-rich (GLA) domain (IPR000294)
- Coagulation factor-like, Gla domain superfamily (IPR017857)
Description
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) [PMID: 18374189, PMID: 11818531, 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 [PMID: 7713897, PMID: 8663165]. Calcium ions induce conformational changes in the GLA domain that and 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].
Proteins known to contain a GLA domain include [PMID: 18373251]:
- Coagulation factor X [PMID: 17723139]
- Coagulation factor VII [PMID: 18642129]
- Coagulation factor IX [PMID: 18680528]
- Coagulation factor XIV (vitamin K-dependent protein C) [PMID: 16156662]
- Vitamin K-dependent protein S [PMID: 16460467]
- Vitamin K-dependent protein Z [PMID: 2403355]
- Prothrombin
- Transthyretin
- Osteocalcin (also known as bone-Gla protein, BGP)
- Matrix Gla protein (MGP) [PMID: 18369157]
- Inter-alpha-trypsin inhibitor heavy chain H2
- Growth arrest-specific protein 6 (Gas-6) [PMID: 9163328]
GO terms
Biological Process
No terms assigned in this category.
Molecular Function
GO:0005509 calcium ion binding
Cellular Component
GO:0005576 extracellular region
Contributing signatures
- SSF57630 (SSF57630)