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http://purl.uniprot.org/citations/12968031http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12968031http://www.w3.org/2000/01/rdf-schema#comment"Activation of factor XI (FXI) by thrombin on stimulated platelets plays a physiological role in hemostasis, providing additional thrombin generation required in cases of severe hemostatic challenge. Using a collection of 53 thrombin mutants, we identified 16 mutants with <50% of the wild-type thrombin FXI-activating activity in the presence of dextran sulfate. These mutants mapped to anion-binding exosite (ABE) I, ABE-II, the Na+-binding site, and the 50-insertion loop. Only the ABE-II mutants showed reduced binding to dextran sulfate-linked agarose. Selected thrombin mutants in ABE-I (R68A, R70A, and R73A), ABE-II (R98A, R245A, and K248A), the 50-insertion loop (W50A), and the Na+-binding site (E229A and R233A) with <10% of the wild-type activity also showed a markedly reduced ability to activate FXI in the presence of stimulated platelets. The ABE-I, 50-insertion loop, and Na+-binding site mutants had impaired binding to FXI, but normal binding to glycocalicin, the soluble form of glycoprotein Ibalpha (GPIb alpha). In contrast, the ABE-II mutants were defective in binding to glycocalicin, but displayed normal binding to FXI. Our data support a quaternary complex model of thrombin activation of FXI on stimulated platelets. Thrombin bound to one GPIb alpha molecule, via ABE-II on its posterior surface, is properly oriented for its activation of FXI bound to a neighboring GPI alpha molecule, via ABE-I on its anterior surface. GPIb alpha plays a critical role in the co-localization of thrombin and FXI and the resultant efficient activation of FXI."xsd:string
http://purl.uniprot.org/citations/12968031http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m306925200"xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/author"Lopez J.A."xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/author"Myles T."xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/author"Walsh P.N."xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/author"Leung L.L."xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/author"Baglia F.A."xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/author"Navaneetham D."xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/author"Yun T.H."xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/pages"48112-48119"xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/title"Thrombin activation of factor XI on activated platelets requires the interaction of factor XI and platelet glycoprotein Ib alpha with thrombin anion-binding exosites I and II, respectively."xsd:string
http://purl.uniprot.org/citations/12968031http://purl.uniprot.org/core/volume"278"xsd:string
http://purl.uniprot.org/citations/12968031http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12968031
http://purl.uniprot.org/citations/12968031http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12968031
http://purl.uniprot.org/uniprot/#_A0A193AU54-mappedCitation-12968031http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12968031
http://purl.uniprot.org/uniprot/#_A0A193AUC0-mappedCitation-12968031http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12968031
http://purl.uniprot.org/uniprot/#_A0A193AUJ5-mappedCitation-12968031http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12968031
http://purl.uniprot.org/uniprot/#_A0A193AUV8-mappedCitation-12968031http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12968031
http://purl.uniprot.org/uniprot/#_E0D851-mappedCitation-12968031http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12968031
http://purl.uniprot.org/uniprot/#_E0D852-mappedCitation-12968031http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12968031
http://purl.uniprot.org/uniprot/#_A5CKE2-mappedCitation-12968031http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12968031
http://purl.uniprot.org/uniprot/#_E0D853-mappedCitation-12968031http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12968031