ArticleProceedings of the National Academy of Sciences of the United States of America2010
Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
84 citing papers in PubMed, 146 citations in OpenAlex.
- Giant viruses encode vitamin K-based redox modules for lipid modification.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Oxidative protein folding and CaCellular and molecular life sciences : CMLS · 2026Review
- The Mechanism and Regulation of Disulfidptosis and Its Role in Disease.Biomedicines · 2026Review
- Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.Biochemistry · 2026Review
- Thiol Isomerases: Enzymatic Mechanisms, Models of Oxidation, and Antagonism by Galloylated Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Recent advances in vascular thiol isomerases: insights into structures, functions in thrombosis and antithrombotic inhibitor development.Thrombosis journal · 2025Review
- 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
- Vitamin K and Calcium Chelation in Vascular Health.Biomedicines · 2023Review
- Comparative membrane proteomics reveals diverse cell regulators concentrated at the nuclear envelope.Life science alliance · 2023Article
- Unfolding the Interactions between Endoplasmic Reticulum Stress and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- Comparative membrane proteomics reveals diverse cell regulators concentrated at the nuclear envelope.bioRxiv : the preprint server for biology · 2023Article
- Introduction of a More Glutaredoxin-like Active Site to PDI Results in Competition between Protein Substrate and Glutathione Binding.Antioxidants (Basel, Switzerland) · 2022Article
- Endoplasmic reticulum oxidoreductin provides resilience against reductive stress and hypoxic conditions by mediating luminal redox dynamics.The Plant cell · 2022Article
- Structural features determining the vitamin K epoxide reduction activity in the VKOR family of membrane oxidoreductases.The FEBS journal · 2022Article
- Vitamin K-Dependent Protein Activation: Normal Gamma-Glutamyl Carboxylation and Disruption in Disease.International journal of molecular sciences · 2022Review
- Introducing Thioredoxin-Related Transmembrane Proteins: Emerging Roles of Human TMX and Clinical Implications.Antioxidants & redox signaling · 2022Review
- Human Vitamin K Epoxide Reductase as a Target of Its Redox Protein.International journal of molecular sciences · 2022Article
- Distinct roles and actions of protein disulfide isomerase family enzymes in catalysis of nascent-chain disulfide bond formation.iScience · 2021Article
- Identification of the Primary Factors Determining theSpecificity of Human VKORC1 Recognition by Thioredoxin-Fold Proteins.International journal of molecular sciences · 2021Article
- Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation.Science (New York, N.Y.) · 2021Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Vitamin K epoxide reductase (VKOR) sustains blood coagulation by reducing vitamin K epoxide to the hydroquinone, an essential cofactor for the gamma-glutamyl carboxylation of many clotting factors. The physiological redox partner of VKOR remains uncertain, but is likely a thioredoxin-like protein. Here, we demonstrate that human VKOR has the same membrane topology as the enzyme from Synechococcus sp., whose crystal structure was recently determined. Our results suggest that, during the redox reaction, Cys43 in a luminal loop of human VKOR forms a transient disulfide bond with a thioredoxin (Trx)-like protein located in the lumen of the endoplasmic reticulum (ER). We screened for redox partners of VKOR among the large number of mammalian Trx-like ER proteins by testing a panel of these candidates for their ability to form this specific disulfide bond with human VKOR. Our results show that VKOR interacts strongly with TMX, an ER membrane-anchored Trx-like protein with a unique CPAC active site. Weaker interactions were observed with TMX4, a close relative of TMX, and ERp18, the smallest Trx-like protein of the ER. We performed a similar screen with Ero1-alpha, an ER-luminal protein that oxidizes the Trx-like protein disulfide isomerase. We found that Ero1-alpha interacts with most of the tested Trx-like proteins, although only poorly with the membrane-anchored members of the family. Taken together, our results demonstrate that human VKOR employs the same electron transfer pathway as its bacterial homologs and that VKORs generally prefer membrane-bound Trx-like redox partners.
Indexed as
Identifiers
What OpenQuestion holds
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.