Mannose-Associated Serine Protease 2 (MASP-2)

Mannose-associated serine protease (MASP), also known as mannan-binding lectin serine protease, is an essential enzyme for the activation of the complement lectin pathway. Currently, 3 MASPs have been discovered, namely MASP-1, MASP-2, and MASP-3. MASP-2 is a zymogen encoded by the MASP-2 gene. It is a single-chain polypeptide of 686 amino acid residues, weighing about 76 kDa. Like MASP-1, MASP-2 also contains 6 discrete domains, that are CUB1 (C1r/C1s, urchin-EGF, and bone morphogenetic protein-1) domain, epidermal growth factor (EGF)-like domain, CUB2 domain, two complement control proteins (CCPs), and serine protease domain from N-terminus to C-terminus. Usually, the MASP-2 monomer forms a mature MASP homodimer, resulting from Ca²⁺-dependent dimerization mediated by the antiparallel CUB1 domain and EGF domain. The two CUB domains are responsible for binding to the collagen-like domains of recognition molecules, and the serine protease domain is the catalytic domain that can cleave substrates.

Among the recognition proteins, MASP-2 can selectively bind to the ficolins and collectins, forming an inactive protein complex. When the complex bind to microbial carbohydrate, zymogen MASP-2 can autoactivate. MASP-1 is essential for its activation under physiological conditions although MASP-2 can autoactivate in vitro. The active MASP-2 cleaves complement C4 and C2 into fragments, generating the C4b2a complex, the C3 convertase in the complement lectin pathway. Besides, MASP-2 is also implicated in the coagulation cascade by cleavage prothrombin. Diseases associated with MASP2 abnormality include MASP-2 Deficiency, complement dysfunctions, and Sporotrichosis.

Fig.1 MASP molecules in the activation of the lectin pathway. (Boldt, 2016)

Reference

1. Boldt, A.B.W.; et al. MASP1 and MASP2. In: Choi S. (eds) Encyclopedia of Signaling Molecules. 2016.