Ask about this productRelated genes to: GGCX Blocking Peptide
- Gene:
- GGCX NIH gene
- Name:
- gamma-glutamyl carboxylase
- Previous symbol:
- -
- Synonyms:
- VKCFD1
- Chromosome:
- 2p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1994-07-04
- Date modifiied:
- 2019-04-23
Related products to: GGCX Blocking Peptide
Related articles to: GGCX Blocking Peptide
- Studies in humans suggest that vitamin K is involved in the regulation of bone remodeling, but the precise mechanism at play remains unknown. In cells, vitamin K functions as a co-factor for the γ-glutamyl carboxylase (GGCX), an enzyme responsible for the conversion of glutamic acid residues (Glu) into γ-carboxyglutamic acid (Gla) residues in secreted proteins. We aim here at determining the role of γ-carboxylation in bone remodeling and at identifying the Gla protein(s) involved. We show that male mice lacking γ-carboxylation specifically in osteoblasts (Ggcx;OCN-Cre) have increased bone mass at 6 months of age due to a reduced number of multinucleated bone resorbing osteoclasts. In co-culture experiments, Ggcx-deficient osteoblasts were less effective than control osteoblasts at supporting osteoclast formation. Among known Gla proteins, we identify GAS6 as an osteoblast-secreted γ-carboxylated factor which signals to differentiating osteoclasts. The GAS6 receptors MerTK and AXL are expressed in pre-osteoclasts and pharmacological inhibitors of AXL and MerTK block osteoclast generation in co-culture. Conversely, recombinant γ-carboxylated GAS6 dose-dependently increases the size of osteoclasts and the number of nuclei per osteoclast in culture. GAS6 marginally affected the induction of osteoclast-specific genes during osteoclast differentiation but significantly increased pre-osteoclast fusion. Finally, increasing bone marrow GAS6 level in transgenic male mice was sufficient to increase the number and size of osteoclasts and to decrease bone mass. This work identifies GAS6 as a novel osteoblast-derived vitamin K-dependent protein regulating osteoclast maturation. - Source: PubMed
Publication date: 2026/04/28
Pata MonicaPham Diep Ngoc ThiLacombe JulieReddy B AshokKim Young WoongAhmed Abeer Gamal AliMurshed MonzurFerron Mathieu
- Source: PubMed
- Gamma-glutamyl carboxylase (GGCX) is the sole enzyme responsible for gamma carboxylation of glutamate in a vitamin K-dependent manner. This process is crucial for blood coagulation, bone metabolism, vascular calcification, and other biological processes because gamma carboxylation is essential for the maturation of clotting factors, anticoagulation factors, and some coagulation-unrelated factors. Despite these essential roles, the catalytic mechanism of GGCX remains incompletely understood. Here, we present the cryo-EM structures of human GGCX complexed with five typical substrates, including two clotting factors and three coagulation-unrelated factors. These structures not only elucidate the recognition mechanism for the propeptide but also reveal three distinct modes for substrate loading. Among them, the GGCX-MGP complex structure reveals a specific mode to load a substrate with an active glutamate residue at the N-terminus of the propeptide. Moreover, these structural observations are supported by our in vitro carboxylation and epoxidation assays. - Source: PubMed
Publication date: 2026/03/27
Zhang WenjieChen QiaoyueZhang BolunQian Hongwu - Pulmonary arterial hypertension (PAH) is a severe disease characterized by elevated pulmonary artery pressure, leading to heart failure and premature death if untreated. Genetic factors significantly contribute to PAH, and several genes have been linked to its development. According to the ClinGen PH-GCEP group, 12 genes have definitive evidence of association with PAH, three have moderate evidence, six have limited evidence, and five remain disputed due to insufficient genetic data. The aim of this study was to analyze variants in genes without definitive evidence in a cohort of 1480 individuals (954 PAH patients and 526 relatives) by next-generation sequencing (NGS). Variants were prioritized through a custom pipeline developed in-house and classification was performed according to ACMG guidelines. A total of 32 different variants were identified in 42 individuals (32 patients and 10 relatives, five of whom developed the disease): Two pathogenic or likely pathogenic variants in ABCC8 and 30 variants of unknown significance (VUS) in 10 genes (ABCC8, AQP1, BMPR1A, BMPR1B, BMP10, FBLN2, NOTCH3, SMAD1, SMAD4 and TET2). On the opposite, no candidate variants were detected in GGCX, KLF2, KLK1 or PDGFD genes. These findings provide further genetic evidence supporting the association of ABCC8 and related genes with PAH, while no candidate variants were detected in GGCX, KLF2, KLK1, or PDGFD. Further research is needed to confirm the functional impact of these variants. - Source: PubMed
Publication date: 2026/03/25
Miranda-Alcaraz LucíaMora-Gómez MónicaGallego-Zazo NataliaCruz-Utrilla AlejandroDel Cerro Marín María JesúsOchoa Parra NuriaMartín de Miguel IreneGutiérrez Ortiz EvaJiménez-Estrada Juan AndrésParra AlejandroCazalla MarioRamos SergioRodríguez-Canó ManuelSilván CristinaVásquez-Amell ValeriaArias PedroNevado Juliánde Jesús Pérez VinicioLapunzina PabloEscribano-Subías PilarTenorio-Castano Jair - Chronic inflammation and ectopic calcification are interrelated processes driving major chronic inflammatory diseases such as cardiovascular and chronic kidney diseases. Gla-rich protein (GRP), a vitamin K-dependent protein (VKDP) with dual anti-inflammatory and anti-calcific properties, has emerged as a promising therapeutic molecule. However, its biomedical development has been limited by difficulties in producing the γ-carboxylated (cGRP) form and by its poor solubility at physiological pH, constraining formulation and delivery. To address these challenges, we established a baculovirus expression vector system (BEVS) designed to couple GRP post-translational maturation with its secretion in extracellular vesicles (EVs). Co-expression of GRP with γ-glutamyl carboxylase (GGCX), vitamin K epoxide reductase (VKOR), and the convertase Furin enabled efficient γ-carboxylation, propeptide removal, and secretion of mature cGRP. GGCX and VKOR were essential for γ-carboxylation, while Furin mediated propeptide processing. EVs were isolated by differential ultracentrifugation into 30 K and 100 K fractions and characterized by NTA, TEM, Western blot, ELISA, and proteomics. All vesicles displayed physical and molecular features resembling mammalian EVs, including canonical EV markers and distinct proteomic profiles, with GRP, GGCX, VKOR, and Furin preferentially enriched in the 30 K population. Functional assays demonstrated that the resulting EVs associated with human THP-1 macrophages and vascular smooth muscle cells (VSMCs) without inducing cytotoxicity, and both cGRP-EVs and uncarboxylated GRP-EVs reduced pro-inflammatory cytokine release while exerting dual anti-inflammatory and anti-mineralizing effects. This study establishes the first bioengineered platform capable of generating functional γ-carboxylated GRP and its vesicular formulation, providing a dual innovation for VKDP research and therapeutic biomaterial development. - Source: PubMed
Publication date: 2026/03/18
Viegas CarlaPichard SimonCarreira JoanaOva AdéliaTroffer-Charlier NathalieMaia Teresa MEdelweiss EvelinaMacedo Anjos LMatos AntónioFaria Tiago QCalado Sofia MMonico CarinaDevos SimonImpens FrancisSchaeffer-Reiss ChristineCianférani SarahPeixoto CristinaPoterszman ArnaudSimes Dina