title: Blood clotting factor IX Niigata: substitution of alanine-390 by valine in the catalytic domain.
abstract: Factor IX Niigata is a mutant factor IX responsible for the moderately severe hemophilia B in a patient who has a normal level of factor IX antigen with reduced clotting activity (1-4% of normal). We reported previously that the purified mutant protein could be converted to the factor IXa beta form by factor XIa/Ca2+ at a rate similar to that in the case of normal factor IX, but the resulting mutant factor IXa beta could not activate factor X in the presence of factor VIII, Ca2+, and phospholipids (Yoshioka, A. et al. (1986) Thromb. Res. 42, 595-604). In the present study, we analyzed factor IX Niigata at the structural level to elucidate the molecular abnormality responsible for the loss of clotting activity. Amino acid sequence analysis of a peptide obtained on lysyl endopeptidase digestion, coupled with subsequent SP-V8 digestion, demonstrated that the alanine at position 390 was substituted by valine in the catalytic domain of the factor IX Niigata molecule.
authors.affiliation: Second Department of Pathology, Nara Medical University.
authors.forename: M
authors.initials: M
authors.lastname: Sugimoto
authors.forename: T
authors.initials: T
authors.lastname: Miyata
authors.forename: S
authors.initials: S
authors.lastname: Kawabata
authors.forename: A
authors.initials: A
authors.lastname: Yoshioka
authors.forename: H
authors.initials: H
authors.lastname: Fukui
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Iwanaga
mesh_terms: D000409:Alanine; D000595:Amino Acid Sequence; D001665:Binding Sites; D005164:Factor IX / Q000235:genetics / Q000302:isolation & purification; D002836:Hemophilia B / Q000097:blood* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000302:isolation & purification; D014633:Valine
chemical_list: D010446:Peptide Fragments; C059032:factor IX Niigata; D005164:Factor IX; D014633:Valine; D000409:Alanine