Disease relevance of MCFD2

• Fragments of YFP were fused to the homooligomeric cargo-receptor lectin endoplasmic reticulum Golgi intermediate compartment (ERGIC)-53, to the ERGIC-53-interacting multi-coagulation factor deficiency protein MCFD2, and to ERGIC-53's cargo glycoprotein cathepsin Z [1].
• Combined factor V - factor VIII deficiency (F5F8D): Compound heterozygosity for two novel truncating mutations in LMAN1 in a consanguineous patient [2].

High impact information on MCFD2

• These findings suggest that the MCFD2-LMAN1 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins [3].
• Here we show that inactivating mutations in MCFD2 cause F5F8D with a phenotype indistinguishable from that caused by mutations in LMAN1 [3].
• LMAN1 and MCFD2 form a protein complex that functions as a cargo receptor ferrying FV and FVIII from the endoplasmic reticulum to the Golgi [4].
• MCFD2 is a soluble EF-hand-containing protein that is retained in the endoplasmic reticulum through its interaction with LMAN1 [5].
• Their efficient secretion requires the membrane lectin ER Golgi intermediate compartment protein-53 (ERGIC-53) and its soluble luminal interaction partner multiple coagulation factor deficiency protein 2 (MCFD2), which form a cargo receptor complex in the early secretory pathway [6].

Biological context of MCFD2

• YFP PCA analysis revealed the oligomerization of ERGIC-53 and its interaction with MCFD2, as well as its lectin-mediated interaction with cathepsin Z [1].
• The results indicate that ERGIC-53 can bind cargo glycoproteins in an MCFD2-independent fashion and suggest that MCFD2 is a recruitment factor for blood coagulation factors V and VIII [6].

Other interactions of MCFD2

• Combined deficiency of factor (F)V and FVIII (F5F8D) and combined deficiency of vitamin K-dependent clotting factors (VKCFD) comprise the vast majority of reported cases of familial multiple coagulation factor deficiencies [7].

References