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PMID: 3461460 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Molecular basis of hemophilia B: a defective enzyme due to an unprocessed propeptide is caused by a point mutation in the factor IX precursor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 16 ·1986-08-00 ·Pages 5803-7

Diuguid DL, Rabiet MJ, Furie BC, Liebman HA, Furie B

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.

MeSH Terms
Amino Acid Sequence DNA/analysis Factor IX/genetics,metabolism Hemophilia A/blood,genetics Humans Kinetics Mutation Phospholipids/blood Protein Binding Protein Conformation Protein Precursors/genetics,metabolism
Chemicals
Phospholipids Protein Precursors factor IX Cambridge Factor IX DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Diuguid D L
Rabiet M J
Furie B C
Liebman H A
Furie B
References (36)
36 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.16.5803
Published
1986-08-00
Pages
5803-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC386383
Subset
IM
Grants
NHLBI NIH HHS · HL18834 · United States
NHLBI NIH HHS · HL21543 · United States
NHLBI NIH HHS · T32 HL07437 · United States
External Links
PubMed source DOI: 10.1073/pnas.83.16.5803 PMC Full Text View journal details
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