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Br J Haematol. 2009 Apr;145(1):15-23. doi: 10.1111/j.1365-2141.2008.07559.x. Epub 2009 Jan 16.

Recent developments in the understanding of the combined deficiency of FV and FVIII.

Author information

1
Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44196, USA. zhangb@ccf.org

Abstract

Combined deficiency of factor V (FV) and factor VIII (FVIII) (F5F8D) is a genetic disorder characterized by mild-to-moderate bleeding and coordinate reduction in plasma FV and FVIII levels, as well as platelet FV level. Recent studies identified mutations in two genes (LMAN1 and MCFD2) as the cause of F5F8D. Though clinically indistinguishable, MCFD2 mutations generally exhibit lower levels of FV and FVIII than LMAN1 mutations. LMAN1 is a mannose-specific lectin that cycles between the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment. MCFD2 is an EF-hand domain protein that forms a calcium-dependent heteromeric complex with LMAN1 in cells. Missense mutations in the EF-hand domains of MCFD2 abolish the interaction with LMAN1. The LMAN1-MCFD2 complex may serve as a cargo receptor for the ER-to-Golgi transport of FV and FVIII, and perhaps a number of other glycoproteins. The B domain of FVIII may be important in mediating its interaction with the LMAN1-MCFD2 complex.

PMID:
19183188
PMCID:
PMC2777536
DOI:
10.1111/j.1365-2141.2008.07559.x
[Indexed for MEDLINE]
Free PMC Article
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