Summary: Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain
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Gla domain Edit Wikipedia article
|Anchoring of Coagulation factor VIIa to the membrane through its GLA domain|
Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain is a protein domain that contains post-translational modifications of many glutamate residues by vitamin K-dependent carboxylation to form gamma-carboxyglutamate (Gla). The Gla residues are responsible for the high-affinity binding of calcium ions. 
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 is found in the middle of the domain which seems to be important for substrate recognition by the carboxylase.
The 3D structures of several Gla domains have been solved. 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.
 Human proteins containing this domain
- ^ Friedman PA, Przysiecki CT (1987). "Vitamin K-dependent carboxylation". Int. J. Biochem. 19 (1): 1–7. doi:10.1016/0020-711X(87)90116-9. PMID 3106112.
- ^ Vermeer C (1990). "Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase". Biochem. J. 266 (3): 625–636. PMC 1131186. PMID 2183788. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1131186.
- ^ Price PA, Fraser JD, Metz-Virca G (1987). "Molecular cloning of matrix Gla protein: implications for substrate recognition by the vitamin K-dependent gamma-carboxylase". Proc. Natl. Acad. Sci. U.S.A. 84 (23): 8335–8339. doi:10.1073/pnas.84.23.8335. PMC 299537. PMID 3317405. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=299537.
- ^ Freedman SJ, Furie BC, Furie B, Baleja JD (1995). "Structure of the metal-free gamma-carboxyglutamic acid-rich membrane binding region of factor IX by two-dimensional NMR spectroscopy". J. Biol. Chem. 270 (14): 7980–7987. doi:10.1074/jbc.270.14.7980. PMID 7713897.
- ^ a b Freedman SJ, Furie BC, Furie B, Baleja JD, Blostein MD, Jacobs M (1996). "Identification of the phospholipid binding site in the vitamin K-dependent blood coagulation protein factor IX". J. Biol. Chem. 271 (27): 16227–16236. doi:10.1074/jbc.271.27.16227. PMID 8663165.
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Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain Provide feedback
This domain is responsible for the high-affinity binding of calcium ions. This domain contains post-translational modifications of many glutamate residues by Vitamin K-dependent carboxylation to form gamma-carboxyglutamate (Gla).
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000294
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) [PUBMED:18374189, PUBMED:11818531, PUBMED: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 [PUBMED: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 [PUBMED:7713897, PUBMED: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 [PUBMED:8663165].
Proteins known to contain a GLA domain include [PUBMED:18373251]:
- Coagulation factor X [PUBMED:17723139]
- Coagulation factor VII [PUBMED:18642129]
- Coagulation factor IX [PUBMED:18680528]
- Coagulation factor XIV (vitamin K-dependent protein C) [PUBMED:16156662]
- Vitamin K-dependent protein S [PUBMED:16460467]
- Vitamin K-dependent protein Z [PUBMED:2403355]
- Osteocalcin (also known as bone-Gla protein, BGP)
- Matrix Gla protein (MGP) [PUBMED:18369157]
- Inter-alpha-trypsin inhibitor heavy chain H2
- Growth arrest-specific protein 6 (Gas-6) [PUBMED:9163328]
|Cellular component||extracellular region (GO:0005576)|
|Molecular function||calcium ion binding (GO:0005509)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
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EGFdomains, and finally a single
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Curation and family details
|Number in seed:||29|
|Number in full:||998|
|Average length of the domain:||41.10 aa|
|Average identity of full alignment:||45 %|
|Average coverage of the sequence by the domain:||11.04 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Gla domain has been found. There are 47 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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