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http://purl.uniprot.org/citations/12773530http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12773530http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12773530http://www.w3.org/2000/01/rdf-schema#comment"C1-inhibitor (C1-Inh) is a serine protease inhibitor (serpin) with a unique, non-conserved N-terminal domain of unknown function. Genetic deficiency of C1-Inh causes hereditary angioedema. A novel type of mutation (Delta 3) in exon 3 of the C1-Inh gene, resulting in deletion of Asp62-Thr116 in this unique domain, was encountered in a hereditary angioedema pedigree. Because the domain is supposedly not essential for inhibitory activity, the unexpected loss-of-function of this deletion mutant was further investigated. The Delta 3 mutant and three additional mutants starting at Pro76, Gly98, and Ser115, lacking increasing parts of the N-terminal domain, were produced recombinantly. C1-Inh76 and C1-Inh98 retained normal conformation and interaction kinetics with target proteases. In contrast, C1-Inh115 and Delta 3, which both lack the connection between the serpin and the non-serpin domain via two disulfide bridges, were completely non-functional because of a complex-like and multimeric conformation, as demonstrated by several criteria. The Delta 3 mutant also circulated in multimeric form in plasma from affected family members. The C1-Inh mutant reported here is unique in that deletion of an entire amino acid stretch from a domain not shared by other serpins leads to a loss-of-function. The deletion in the unique N-terminal domain results in a "multimerization phenotype" of C1-Inh, because of diminished stability of the central beta-sheet. This phenotype, as well as the location of the disulfide bridges between the serpin and the non-serpin domain of C1-Inh, suggests that the function of the N-terminal region may be similar to one of the effects of heparin in antithrombin III, maintenance of the metastable serpin conformation."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m302977200"xsd:string
http://purl.uniprot.org/citations/12773530http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m302977200"xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Abrahams J.P."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Abrahams J.P."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Eldering E."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Eldering E."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Bos I.G.A."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Bos I.G.A."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Hack C.E."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Hack C.E."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Lubbers Y.T.P."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Lubbers Y.T.P."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Roem D."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/author"Roem D."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/pages"29463-29470"xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/pages"29463-29470"xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/title"The functional integrity of the serpin domain of C1-inhibitor depends on the unique N-terminal domain, as revealed by a pathological mutant."xsd:string
http://purl.uniprot.org/citations/12773530http://purl.uniprot.org/core/title"The functional integrity of the serpin domain of C1-inhibitor depends on the unique N-terminal domain, as revealed by a pathological mutant."xsd:string
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