Molecular Basis of Hemophilia B: a Defective Enzyme Due to an Unprocessed Propeptide is Caused by a Point Mutation in the Factor IX Precursor

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1986 Aug 1

PMID 3461460

Citations 26

Authors

D L Diuguid

M J Rabiet

B C Furie

H A Liebman

B Furie

Affiliations

Soon will be listed here.

Abstract

A mutant factor IX, designated factor IXCambridge, was isolated from a patient with hemophilia B. This protein includes an 18-residue propeptide attached to the NH2 terminus of factor IX. A point mutation at residue -1, from an arginine to a serine, precludes cleavage of the propeptide by a processing protease and interferes with gamma-carboxylation of the factor IX, indicating the importance of the leader sequence in substrate recognition by the vitamin K-dependent carboxylase. This represents an example of an enzyme defect due to the presence of a point mutation in a precursor protein (preproenzyme) that is the cause of a human hereditary disease. This defect will serve as a prototype for understanding the molecular basis of some forms of hemophilia and other hereditary enzyme deficiencies.

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