Defective gamma-carboxylation of F9

Stable Identifier
R-HSA-9673240
Type
Pathway
Species
Homo sapiens
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Naturally occurring hemophilia B (HB)-associated point mutations in the FIX propeptide sequence reduce affinity to gamma-glutamyl carboxylase (GGCX) resulting in reduced γ-carboxylation and aberrant propeptide processing (Bentley AK et al. 1986; Rabiet MJ et al. 1987; Diuguid DL et al. 1986; Ware J et al. 1989; de la Salle C et al. 1993). Unprocessed FIX variants such as F9 N43Q/L or F9 N46S, circulate with the attached propeptide and show delayed FIX activation (Bentley AK et al. 1986; Diuguid DL et al. 1986; Ware J et al. 1989; de la Salle C et al. 1993).

Literature References
PubMed ID Title Journal Year
3667614 Effect of propeptide mutations on post-translational processing of factor IX. Evidence that beta-hydroxylation and gamma-carboxylation are independent events

Rabiet, MJ, Jorgensen, MJ, Furie, B, Furie, BC

J. Biol. Chem. 1987
2738071 Factor IX San Dimas. Substitution of glutamine for Arg-4 in the propeptide leads to incomplete gamma-carboxylation and altered phospholipid binding properties.

Ware, J, Diuguid, DL, Liebman, HA, Rabiet, MJ, Kasper, CK, Furie, BC, Furie, B, Stafford, DW

J Biol Chem 1989
8295821 The Arg-4 mutant factor IX Strasbourg 2 shows a delayed activation by factor XIa

de la Salle, C, Charmantier, JL, Ravanat, C, Ohlmann, P, Hartmann, ML, Schuhler, S, Bischoff, R, Ebel, C, Roecklin, D, Balland, A

Nouv Rev Fr Hematol 1993
9169594 Modification of the N-terminus of human factor IX by defective propeptide cleavage or acetylation results in a destabilized calcium-induced conformation: effects on phospholipid binding and activation by factor XIa

Wojcik, EG, Van Den Berg, M, Poort, SR, Bertina, RM

Biochem. J. 1997
2788012 Defective propeptide processing and abnormal activation underlie the molecular pathology of factor IX Troed-y-Rhiw

Liddell, MB, Lillicrap, DP, Peake, IR, Bloom, AL

Br. J. Haematol. 1989
Participants
Participant Of
Disease
Name Identifier Synonyms
hemophilia B 12259 factor IX deficiency, Congenital factor IX deficiency, deficiency, functional factor IX, Congenital factor IX disorder
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