GGCX

This gene encodes an integral membrane protein of the rough endoplasmic reticulum that carboxylates glutamate residues of vitamin K-dependent proteins to gamma carboxyl glutamate, a modification that is required for their activity. The vitamin K-dependent protein substrates have a propeptide that binds the enzyme, with carbon dioxide, dioxide, and reduced vitamin K acting as co-substrates. Vitamin K-dependent proteins affect a number of physiologic processes including blood coagulation, prevention of vascular calcification, and inflammation. Allelic variants of this gene have been associated with pseudoxanthoma elasticum-like disorder with associated multiple coagulation factor deficiency. Alternative splicing results in multiple transcript variants.

Full Name

Gamma-Glutamyl Carboxylase

Function

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.

Biological Process

Blood coagulation Source: ProtInc
Cellular protein modification process Source: ProtInc
Peptidyl-glutamic acid carboxylation Source: GO_Central

Cellular Location

Endoplasmic reticulum membrane

Involvement in disease

Combined deficiency of vitamin K-dependent clotting factors 1 (VKCFD1):
VKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K.
Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency (PXEL-MCFD):
Characterized by hyperlaxity of the skin involving the entire body. Important phenotypic differences with classical PXE include much more severe skin laxity with spreading toward the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. Moreover, detailed electron microscopic analyzes revealed that alterations of elastic fibers as well as their mineralization are slightly different from those in classic PXE.

Topology

Cytoplasmic: 2-60
Helical: 61-81
Lumenal: 82-113
Helical: 114-134
Cytoplasmic: 135-136
Helical: 137-157
Lumenal: 158-292
Helical: 293-313
Cytoplasmic: 314-361
Helical: 362-382
Lumenal: 383-758