Blood clotting factor IX Nagoya 3: the molecular defect of zymogen activation caused by an arginine-145 to histidine substitution.
Factor IX Nagoya 3 (IX Nagoya 3) is a natural mutant of factor IX recognized in a patient with moderately severe hemophilia B. The patient had 0.60 units/ml of factor IX antigen and 2-5% of clotting activity. IX Nagoya 3 was purified from the patient's plasma by immunoaffinity chromatography with an anti-factor IX monoclonal antibody column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that the treatment of IX Nagoya 3 with factor XIa/calcium ions resulted in cleavage only at the Arg180-Val181 bond. The amino acid sequence analysis of one of the lysyl endopeptidase peptides derived from IX Nagoya 3 revealed that Arg-145 is replaced by His. This substitution impairs the cleavage between the light chain and the activation peptide by factor XIa/calcium ions.
Suehiro
K
K
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Miyata
T
T
Takeya
H
H
Takamatsu
J
J
Saito
H
H
Murakawa
M
M
Okamura
T
T
Niho
Y
Y
Iwanaga
S
S
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D005164:Factor IX / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015945:Factor XIa / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009154:Mutation
C068395:factor IX Nagoya 3; D005164:Factor IX; D015945:Factor XIa; D002118:Calcium