Biochemical and cellular consequences of the antithrombin p.Met1? mutation identified in a severe thrombophilic family.

ABSTRACT: Nature is always the best inspiration for basic research. A family with severe thrombosis and antithrombin deficiency, the strongest anticoagulant, carried a new mutation affecting the translation-start codon of SERPINC1, the gene encoding antithrombin. Expression of this variant in a eukaryotic cell system produced three different antithrombins. Two downstream methionines were used as alternative initiation codons, generating highly expressed small aglycosylated antithrombins with cytoplasmic localization. Wild-type antithrombin was generated by the use of the mutated AUU as initiation codon. Actually, any codon except for the three stop codons might be used to initiate translation in this strong Kozak context. We show unexpected consequences of natural mutations affecting translat

SUBMITTER: Navarro-Fernandez J 

PROVIDER: S-EPMC6145704 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature