dc.contributor.author | Ramsay, Andrew J. | |
dc.contributor.author | Quesada, Victor | |
dc.contributor.author | Sanchez, Mayka | |
dc.contributor.author | Garabaya, Cecilia | |
dc.contributor.author | Sardà, María P. | |
dc.contributor.author | Baiget, Montserrat | |
dc.contributor.author | Remacha, Angel | |
dc.contributor.author | Velasco, Gloria | |
dc.contributor.author | López-Otín, Carlos | |
dc.date.accessioned | 2024-01-31T13:40:49Z | |
dc.date.available | 2024-01-31T13:40:49Z | |
dc.date.issued | 2009 | |
dc.identifier.citation | Ramsay, Andrew J.; Quesada, Victor; Sanchez, Mayka [et al.]. Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms. Human Molecular Genetics, 2009, 18(19), p. 3673-3683. Disponible en: <https://academic.oup.com/hmg/article/18/19/3673/2386335?login=true>. Fecha de acceso: 31 ene. 2024. DOI: 10.1093/hmg/ddp315 | ca |
dc.identifier.issn | 0964-6906 | ca |
dc.identifier.uri | http://hdl.handle.net/20.500.12328/3995 | |
dc.description.abstract | Mutations leading to abrogation of matriptase-2 proteolytic activity in humans are associated with an iron-refractory iron deficiency anemia (IRIDA) due to elevated hepcidin levels. Here we describe two novel heterozygous mutations within the matriptase-2 ( TMPRSS6 ) gene of monozygotic twin girls exhibiting an IRIDA phenotype. The first is the frameshift mutation (P686fs) caused by the insertion of the four nucleotides CCCC in exon 16 (2172_2173insCCCC) that is predicted to terminate translation before the catalytic serine. The second mutation is the di-nucleotide substitution c.467C>A and c.468C>T in exon 3 that causes the missense mutation A118D in the SEA domain of the extracellular stem region of matriptase-2. Functional analysis of both variant matriptase-2 proteases has revealed that they lead to ineffective suppression of hepcidin transcription. We also demonstrate that the A118D SEA domain mutation causes an intra-molecular structural imbalance that impairs matriptase-2 activation. Collectively, these results extend the pattern of TMPRSS6 mutations associated with IRIDA and functionally demonstrate that mutations affecting protease regions other than the catalytic domain may have a profound impact in the regulatory role of matriptase-2 during iron deficiency. | ca |
dc.format.extent | 10 | ca |
dc.language.iso | eng | ca |
dc.publisher | Oxford University Press | ca |
dc.relation.ispartof | Human Molecular Genetics | ca |
dc.relation.ispartofseries | 18;19 | |
dc.rights | © 2024 Oxford University Press | ca |
dc.subject.other | Fenotip | ca |
dc.subject.other | Mutació del ferro | ca |
dc.subject.other | Anèmia per deficiència de ferro | ca |
dc.subject.other | Endopeptidases | ca |
dc.subject.other | Exons | ca |
dc.subject.other | Pèptid | ca |
dc.subject.other | Hidrolases | ca |
dc.subject.other | Hepcidina | ca |
dc.subject.other | Proteòlisi | ca |
dc.subject.other | Cognició social i avaluació emocional | ca |
dc.subject.other | Fenotipo | ca |
dc.subject.other | Mutación del hierro | ca |
dc.subject.other | Deficiencia de hierro | ca |
dc.subject.other | Anemia | ca |
dc.subject.other | Endopeptidasas | ca |
dc.subject.other | Exones | ca |
dc.subject.other | Péptido | ca |
dc.subject.other | Hidrolasas | ca |
dc.subject.other | Hepcidina | ca |
dc.subject.other | Proteólisis | ca |
dc.subject.other | Cognición social y evaluación emocional | ca |
dc.subject.other | Phenotype | ca |
dc.subject.other | Iron mutation | ca |
dc.subject.other | Iron deficiency | ca |
dc.subject.other | Anemia | ca |
dc.subject.other | Endopeptidases | ca |
dc.subject.other | Exons | ca |
dc.subject.other | Peptide | ca |
dc.subject.other | Hydrolases | ca |
dc.subject.other | Hepcidin | ca |
dc.subject.other | Proteolysis | ca |
dc.subject.other | Social cognition and emotional assessment | ca |
dc.title | Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms | ca |
dc.type | info:eu-repo/semantics/article | ca |
dc.description.version | info:eu-repo/semantics/publishedVersion | ca |
dc.rights.accessLevel | info:eu-repo/semantics/openAccess | |
dc.embargo.terms | cap | ca |
dc.subject.udc | 61 | ca |
dc.identifier.doi | https://dx.doi.org/10.1093/hmg/ddp315 | ca |