LMAN1 is a molecular chaperone for the secretion of coagulation factor VIII.
Article Details
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Cunningham MA, Pipe SW, Zhang B, Hauri HP, Ginsburg D, Kaufman RJ
LMAN1 is a molecular chaperone for the secretion of coagulation factor VIII.
J Thromb Haemost. 2003 Nov;1(11):2360-7.
- PubMed ID
- 14629470 [ View in PubMed]
- Abstract
Combined deficiency of both coagulation factors (F)V and VIII is a rare autosomal recessive bleeding disorder caused by null expression of LMAN1 (previously termed ERGIC-53) in a majority of affected individuals. Previously, a requirement for a functional LMAN1 cycling pathway between the ER and Golgi was demonstrated for efficient secretion of FV and FVIII (Moussalli et al. J Biol Chem 1999; 274: 32569), however, the molecular nature of the interaction between LMAN1 and its cargo was not characterized. Using coimmunoprecipitation of LMAN1 and FVIII from transfected HeLa and COS-1 cells, we demonstrate an interaction between LMAN1 and FVIII in vivo. The interaction was mediated via high mannose-containing asparagine-linked oligosaccharides that are densely situated within the B domain of FVIII, as well as protein-protein interactions. These results are interpreted based on the recent determination of the crystal structure of the carbohydrate recognition domain of LMAN1.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Antihemophilic factor, human recombinant Protein ERGIC-53 Protein Humans UnknownChaperoneDetails Lonoctocog alfa Protein ERGIC-53 Protein Humans UnknownChaperoneDetails Moroctocog alfa Protein ERGIC-53 Protein Humans UnknownChaperoneDetails