title: Mannan-binding-lectin-associated serine proteases, characteristics and disease associations.
abstract: Mannan-binding lectin (MBL)-associated serine proteases (MASPs) circulate in plasma as zymogens in complexes with MBL and with L- and H-ficolin. Upon binding of MBL or ficolin to pathogen-associated molecular patterns, the MASPs are activated. MASP-2 can now cleave C4 and C2 to generate the C3 convertase, C4bC2b. The functions of the other two MASPs, MASP-1 and MASP-3 have not been elucidated. MASP-1 can cleave C2, and with low efficiency also C3, and may serve a function through direct C3 activation. No natural substrate for MASP-3 has been identified. MBL deficiency, occurring at a frequency of about 10%, is the most common congenital immunodeficiency and is associated with susceptibility to infections and autoimmune disorders. Inherited MASP-2 deficiency has been described as the result of a mutation causing the exchange of aspartic acid with a glycine at position 105, a position in the first domain, CUB1, involved in calcium binding. This mutation abolishes the binding to MBL and ficolins, and deprives MASP-2 of functional activity. The index case suffered from recurrent severe infections and autoimmune reactions. The gene frequency of the mutation among Caucasians is 3.6%. It is not found in Chinese, who present a different mutation also associated with MASP-2 deficiency.
authors.affiliation: Department of Medical Microbiology and Immunology, Wilhelm Meyers Allé, University of Aarhus, 8000 Aarhus, Denmark. rs@microbiology.au.dk
authors.forename: Rikke
authors.initials: R
authors.lastname: Sørensen
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.forename: Jens C
authors.initials: JC
authors.lastname: Jensenius
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D037582:Complement Pathway, Mannose-Binding Lectin; D019281:Dimerization; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000151:congenital / Q000235:genetics / Q000276:immunology; D037102:Lectins / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000276:immunology; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008958:Models, Molecular; D046912:Multiprotein Complexes; D009154:Mutation; D020836:Protein Structure, Quaternary; D013379:Substrate Specificity; D000097604:Ficolins
chemical_list: D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D046912:Multiprotein Complexes; D000097604:Ficolins; C105296:MASP2 protein, human