ReviewInternational journal of molecular sciences2022
Vitamin K-Dependent Protein Activation: Normal Gamma-Glutamyl Carboxylation and Disruption in Disease.
Review in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- Article
- Vitamin K Deficiency and Thrombophilia in Pregnancy: A Fine Balance Between Bleeding and Thrombus Formation-Insights from a Narrative Review.International journal of molecular sciences · 2026Review
- Identification of PRRG1 as a possible molecular target of pancreatic cancer.Cell death & disease · 2026Article
- Vitamin K2 Supplementation Reduces Cardiometabolic Risk Factors in Young Adults with Overweight and Obesity-A Randomized Placebo-Controlled Trial.Biomedicines · 2026Article
- Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice.Bone research · 2026Article
- Structural basis for the carboxylation and epoxidation of human gamma-glutamyl carboxylase.Nature communications · 2026Article
- Molecular insights into the comorbidity of vitamin K-dependent clotting factor deficiency and chondrodysplasia punctata.Journal of thrombosis and haemostasis : JTH · 2025Article
- Selective targeting of coagulation factor X Gla domain by negatively charged gold nanoparticles: a novel method for controlled antithrombotic therapy.Materials today. Bio · 2025Article
- Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase.Nature communications · 2025Article
- Advances in Transdermal Drug Delivery Systems for Antithrombotic Therapy: A Systematic Review.ACS pharmacology & translational science · 2025Review
- Osteocalcin has many tricks to get γ-carboxylated.Cell research · 2025Article
- Micro-nutrient sufficiency in mothers and babies: management of deficiencies while avoiding overload during pregnancy.Frontiers in nutrition · 2025Review
- Vitamin K-dependent gamma-carboxyglutamic acid protein 1 promotes pancreatic ductal adenocarcinoma progression through stabilizing oncoprotein KRAS and tyrosine kinase receptor EGFR.Clinical and translational medicine · 2025Article
- Vitamin K: Calcium Metabolism Modulator for Menopausal Women.Journal of menopausal medicine · 2024Review
- Modification of Gas6 Protein in the Brain by a Functional Endogenous Tissue Vitamin K Cycle.Cells · 2024Article
- Is a Vitamin K Epoxide Reductase Complex Subunit 1 (International journal of molecular sciences · 2024Article
- Vitamin K Epoxide Reductase Complex-Protein Disulphide Isomerase Assemblies in the Thiol-Disulphide Exchange Reactions: Portrayal of Precursor-to-Successor Complexes.International journal of molecular sciences · 2024Article
- Inorganic pyrophosphate plasma levels in patients with GGCX-associated PXE-like phenotypes.Frontiers in genetics · 2024Article
- Characterization of Gla proteoforms and non-Gla peptides of gamma carboxylated proteins: Application to quantification of prothrombin proteoforms in human plasma.Analytica chimica acta · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Vitamin K-dependent (VKD) proteins undergo an unusual post-translational modification, which is the conversion of specific Glu residues to carboxylated Glu (Gla). Gla generation is required for the activation of VKD proteins, and occurs in the endoplasmic reticulum during their secretion to either the cell surface or from the cell. The gamma-glutamyl carboxylase produces Gla using reduced vitamin K, which becomes oxygenated to vitamin K epoxide. Reduced vitamin K is then regenerated by a vitamin K oxidoreductase (VKORC1), and this interconversion of oxygenated and reduced vitamin K is referred to as the vitamin K cycle. Many of the VKD proteins support hemostasis, which is suppressed during therapy with warfarin that inhibits VKORC1 activity. VKD proteins also impact a broad range of physiologies beyond hemostasis, which includes regulation of calcification, apoptosis, complement, growth control, signal transduction and angiogenesis. The review covers the roles of VKD proteins, how they become activated, and how disruption of carboxylation can lead to disease. VKD proteins contain clusters of Gla residues that form a calcium-binding module important for activity, and carboxylase processivity allows the generation of multiple Glas. The review discusses how impaired carboxylase processivity results in the pseudoxanthoma elasticum-like disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.