Vitamin K-dependent gamma-carboxylase (GGCX)
The protein contains 758 amino acids for an estimated molecular weight of 87561 Da.
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
No binding partner found
The reference OMIM entry for this protein is 137167
Gamma-glutamyl carboxylase; ggcx
DESCRIPTION
Gamma-glutamyl carboxylase accomplishes the posttranslational modification required for the activity of all of the vitamin K-dependent proteins. These include some of the blood coagulation and anticoagulation proteins as well as bone gamma-carboxyglutamic acid (Gla) protein (BGLAP; 112260) and bone matrix protein (MGP; 154870) (summary by Wu et al., 1991).CLONING
Wu et al. (1991) cloned a cDNA corresponding to GGCX and showed that expression resulted in an increase in carboxylase activity in microsomes of transfected cells. The GGCX gene encodes a 758-residue integral membrane protein with 3 transmembrane domains near its amino terminus.GENE STRUCTURE
Wu et al. (1997) found that the GGCX gene spans 13 kb and contains 15 exons.GENE FUNCTION
Vitamin K is a necessary cofactor for the hepatic carboxylation of glutamic acid residues in a number of proteins, including the procoagulants factors II, VII, IX, and X; the anticoagulants protein C and protein S; and other proteins such as osteocalcin and matrix Gla protein This carboxylation is required for normal hemostasis, because it enables calcium binding and attachment of the procoagulants and anticoagulants to phospholipids. Gamma-glutamyl carboxylase is an integral membrane microsomal enzyme located in the rough endoplasmic reticulum. It carboxylates glutamate residues located in the Gla domain of vitamin K-dependent coagulation factors. The carboxylation reaction is dependent on reduced vitamin K, which is converted to vitamin K epoxide during carboxylation, and must be regenerated by the vitamin K epoxide reductase (EPHX1; 132810) for carboxylation to continue (summary by Brenner et al., 1998).MAPPING
Kuo et al. (1995) mapped the GGCX gene to chromosome 2 using human/rodent somatic cell hybrid DNAs and localized it to 2p12 by fluorescence in situ hybridization.MOLECULAR GENETICS
- Combined Deficiency of Vitamin K-Dependent Clotting Factors 1 Brenner et al. (1990) described an offspring of a consanguineous marriage with hereditary combined deficiency of vitamin K-dependent procoagulants (VKCFD1; 277450). Epoxide reductase function was found to be normal. Impairment of Gla-dependent calcium reduction binding was suggested by cross-immunoelectrophoresis studies of prothrombin. They therefore suggested that the abnormality in the kindred resulted from GGCX deficiency, with autosomal recessive inheritance. Brenner et al. (1998) identified a homozygous T-to-G transversion at codon 394 of the GGCX gene that resulted in substitution of arginine for leucine (R394L; 137167.0001). The mutation was identified in all 4 children with clinical and analytical findings of hereditary deficiency of all vitamin K-dependent coagulation factors. This was the first reported mutation in the GGCX gene. Rost et al. (2004) reported what they stated to be the third case of hereditary combined deficiency of the vitamin K-dependent coagulation factors (VKCFD1) caused by mutation in the GGCX gene (137167.0003-137167.0004). - PXE-like Disorder with Multiple Coagulation Factor Deficiency Vanakker et al. (2007) described a pseudoxanthoma elasticum-like phenotype with associated multiple coagulation factor deficiency (610842). They found mutations in the GGCX gene in 6 of 7 patients with this phenotype and compared the findings in these 6 patients with the 4 previously described in the literature. None of the patients had mutations in the AB ... More on the omim web site
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 137167 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).