ArticleBlood2014
TFPI cofactor function of protein S: essential role of the protein S SHBG-like domain.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 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
- Pedigree analysis of cerebral venous sinus thrombosis associated with compound heterozygous hereditary protein S deficiency.Annals of hematology · 2026Article
- Mechanisms of thrombin inhibition by protein S and the TFPIα-fVshort-protein S complex.Biophysical journal · 2026Article
- Laminin G domains define a critical interface for protein S-mediated factor IXa inhibition.Journal of thrombosis and haemostasis : JTH · 2026Article
- The impact of protein S and tissue factor pathway inhibitor on coagulation, assessed with thrombin generation, in women starting combined oral contraceptives.Research and practice in thrombosis and haemostasis · 2025Article
- Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Unfolded von Willebrand factor binds protein S and reduces anticoagulant activity.Blood vessels, thrombosis & hemostasis · 2025Article
- Examining downstream effects of concizumab in hemophilia A with a mathematical modeling approach.Journal of thrombosis and haemostasis : JTH · 2025Article
- TFPIα anticoagulant function is highly dependent on protein S in vivo.Science advances · 2024Article
- Factor V variants in bleeding and thrombosis.Research and practice in thrombosis and haemostasis · 2024Article
- The impact ofResearch and practice in thrombosis and haemostasis · 2023Article
- Genome-wide association study of varicose veins identifies a protective missense variant in GJD3 enriched in the Finnish population.Communications biology · 2023Article
- The first laminin G-like domain of protein S is essential for binding and activation of Tyro3 receptor and intracellular signalling.Biochemistry and biophysics reports · 2022Article
- Proteomics of Coagulopathy Following Injury Reveals Limitations of Using Laboratory Assessment to Define Trauma-Induced Coagulopathy to Predict Massive Transfusion.Annals of surgery open : perspectives of surgical history, education, and clinical approaches · 2022Article
- Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP.Blood advances · 2022Article
- A thrombophilia family with protein S deficiency due to protein translation disorders caused by a Leu607Ser heterozygous mutation in PROS1.Thrombosis journal · 2021Article
- Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population.Frontiers in cardiovascular medicine · 2021Article
- The roles of factor Va and protein S in formation of the activated protein C/protein S/factor Va inactivation complex.Journal of thrombosis and haemostasis : JTH · 2019Article
- Measurement of plasma and platelet tissue factor pathway inhibitor, factor V and Protein S in people with haemophilia.Haemophilia : the official journal of the World Federation of Hemophilia · 2019Article
- Defective fibrin deposition and thrombus stability in BambiJournal of thrombosis and haemostasis : JTH · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Protein S is a cofactor for tissue factor pathway inhibitor (TFPI), accelerating the inhibition of activated factor X (FXa). TFPI Kunitz domain 3 residue Glu226 is essential for enhancement of TFPI by protein S. To investigate the complementary functional interaction site on protein S, we screened 44 protein S point, composite or domain swap variants spanning the whole protein S molecule for their TFPI cofactor function using a thrombin generation assay. Of these variants, two protein S/growth arrest-specific 6 chimeras, with either the whole sex hormone-binding globulin (SHBG)-like domain (Val243-Ser635; chimera III) or the SHBG laminin G-type 1 subunit (Ser283-Val459; chimera I), respectively, substituted by the corresponding domain in growth arrest-specific 6, were unable to enhance TFPI. The importance of the protein S SHBG-like domain (and its laminin G-type 1 subunit) for binding and enhancement of TFPI was confirmed in FXa inhibition assays and using surface plasmon resonance. In addition, protein S bound to C4b binding protein showed greatly reduced enhancement of TFPI-mediated inhibition of FXa compared with free protein S. We show that binding of TFPI to the protein S SHBG-like domain enables TFPI to interact optimally with FXa on a phospholipid membrane.
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.