ArticleBlood2015
Protein C Thr315Ala variant results in gain of function but manifests as type II deficiency in diagnostic assays.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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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.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Serum Proteomic Signatures in Umbilical Cord Blood of Preterm Neonates Delivered by Women with Gestational Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- diaPASEF Proteomics and Feature Selection for the Description of Sputum Proteome Profiles in a Cohort of Different Subtypes of Lung Cancer Patients and Controls.International journal of molecular sciences · 2022Article
- [Clinical phenotype and gene mutation analysis of 12 patients with hereditary protein C deficiency in different families].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2022Article
- Acute Endoplasmic Reticulum Stress Induces Inflammation Reaction, Complement System Activation, and Lipid Metabolism Disorder of Piglet Livers: A Proteomic Approach.Frontiers in physiology · 2022Article
- Role of Gly197 in the structure and function of protein C.Biochimica et biophysica acta. General subjects · 2021Article
- Article
- Allotype-specific processing of the CD16a N45-glycan from primary human natural killer cells and monocytes.Glycobiology · 2020Article
- Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.Haematologica · 2020Article
- Gly197Arg mutation in protein C causes recurrent thrombosis in a heterozygous carrier.Journal of thrombosis and haemostasis : JTH · 2020Article
- Glycoproteogenomics: A Frequent Gene Polymorphism Affects the Glycosylation Pattern of the Human Serum Fetuin/α-2-HS-Glycoprotein.Molecular & cellular proteomics : MCP · 2019Article
- Expression Characteristics of Genes Hypermethylated and Downregulated in Rat Liver Specific to Nongenotoxic Hepatocarcinogens.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Loss and gain of N-linked glycosylation sequons due to single-nucleotide variation in cancer.Scientific reports · 2018Article
- Gly74Ser mutation in protein C causes thrombosis due to a defect in protein S-dependent anticoagulant function.Thrombosis and haemostasis · 2017Article
- Rational Design of Protein C Activators.Scientific reports · 2017Article
- Paradoxical bleeding and thrombotic episodes of dysprothrombinaemia due to a homozygous Arg382His mutation.Thrombosis and haemostasis · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein C (PC) is a vitamin K-dependent plasma glycoprotein, which upon activation by thrombin in complex with thrombomodulin (TM), regulates the coagulation cascade through a feedback loop inhibition mechanism. PC deficiency is associated with an increased risk of venous thromboembolism (VTE). A recent cohort study aimed at establishing a normal PC range identified a healthy PC-deficient subject whose PC antigen level of 65% and activity levels of 50% (chromogenic assay) and 36% (clotting assay) were markedly low. The proband has a negative family history of VTE. Genetic analysis revealed the proband has a heterozygous missense mutation in which Thr-315 of the PC heavy chain has been substituted with Ala. We expressed this mutant in HEK-293 cells and purified it to homogeneity. A similar decrease in both anticoagulant and anti-inflammatory activities of the activated protein C mutant was observed in plasma- and cell-based assays. Interestingly, we discovered if functional assays were coupled to PC activation by the thrombin-TM complex, the variant exhibits improved activities in all assays. Sequence analysis revealed Thr-315 is a consensus N-linked glycosylation site for Asn-313 and that its elimination significantly (∼four- to fivefold) improves the maximum velocity of PC activation by the thrombin-TM complex, explaining the basis for the proband's negative VTE pedigree.
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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.