4ygc

Structural highlights

Disease

[LMAN1_HUMAN] Defects in LMAN1 are THE cause of factor V and factor VIII combined deficiency type 1 (F5F8D1) [MIM:227300]; also known as multiple coagulation factor deficiency I (MCFD1). F5F8D1 is an autosomal recessive blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal.^[1] [MCFD2_HUMAN] Defects in MCFD2 are a cause of factor V and factor VIII combined deficiency type 2 (F5F8D2) [MIM:613625]; also known as multiple coagulation factor deficiency 2 (MCFD2). F5F8D2 is a blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal.^{[2] [3]}

Function

[LMAN1_HUMAN] Mannose-specific lectin. May recognize sugar residues of glycoproteins, glycolipids, or glycosylphosphatidyl inositol anchors and may be involved in the sorting or recycling of proteins, lipids, or both. The LMAN1-MCFD2 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins.^{[4] [5]} [MCFD2_HUMAN] The MCFD2-LMAN1 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins. Plays a role in the secretion of coagulation factors.^[6]

References

1. ↑ Nichols WC, Terry VH, Wheatley MA, Yang A, Zivelin A, Ciavarella N, Stefanile C, Matsushita T, Saito H, de Bosch NB, Ruiz-Saez A, Torres A, Thompson AR, Feinstein DI, White GC, Negrier C, Vinciguerra C, Aktan M, Kaufman RJ, Ginsburg D, Seligsohn U. ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families. Blood. 1999 Apr 1;93(7):2261-6. PMID:10090935
2. ↑ Zhang B, Cunningham MA, Nichols WC, Bernat JA, Seligsohn U, Pipe SW, McVey JH, Schulte-Overberg U, de Bosch NB, Ruiz-Saez A, White GC, Tuddenham EG, Kaufman RJ, Ginsburg D. Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nat Genet. 2003 Jun;34(2):220-5. PMID:12717434 doi:10.1038/ng1153
3. ↑ Guy JE, Wigren E, Svard M, Hard T, Lindqvist Y. New insights into multiple coagulation factor deficiency from the solution structure of human MCFD2. J Mol Biol. 2008 Sep 12;381(4):941-55. Epub 2008 Jun 20. PMID:18590741 doi:10.1016/j.jmb.2008.06.042
4. ↑ Nufer O, Kappeler F, Guldbrandsen S, Hauri HP. ER export of ERGIC-53 is controlled by cooperation of targeting determinants in all three of its domains. J Cell Sci. 2003 Nov 1;116(Pt 21):4429-40. Epub 2003 Sep 16. PMID:13130098 doi:10.1242/jcs.00759
5. ↑ Zhang B, Cunningham MA, Nichols WC, Bernat JA, Seligsohn U, Pipe SW, McVey JH, Schulte-Overberg U, de Bosch NB, Ruiz-Saez A, White GC, Tuddenham EG, Kaufman RJ, Ginsburg D. Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nat Genet. 2003 Jun;34(2):220-5. PMID:12717434 doi:10.1038/ng1153
6. ↑ Zhang B, Cunningham MA, Nichols WC, Bernat JA, Seligsohn U, Pipe SW, McVey JH, Schulte-Overberg U, de Bosch NB, Ruiz-Saez A, White GC, Tuddenham EG, Kaufman RJ, Ginsburg D. Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nat Genet. 2003 Jun;34(2):220-5. PMID:12717434 doi:10.1038/ng1153