Two Constituents of the Initiation Complex of the Mannan-Binding Lectin Activation Pathway of Complement Are Encoded by a Single Structural Gene

Abstract

Mannan-binding lectin (MBL) forms a multimolecular complex with at least two MBL-associated serine proteases, MASP-1 and MASP-2. This complex initiates the MBL pathway of complement activation by binding to carbohydrate structures present on bacteria, yeast, and viruses. MASP-1 and MASP-2 are composed of modular structural motifs similar to those of the C1q-associated serine proteases C1r and C1s. Another protein of 19 kDa with the same N-terminal sequence as the 76-kDa MASP-2 protein is consistently detected as part of the MBL/MASP complex. In this study, we present the primary structure of this novel MBL-associated plasma protein of 19 kDa, MAp19, and demonstrate that MAp19 and MASP-2 are encoded by two different mRNA species generated by alternative splicing/polyadenylation from one structural gene.

The Lectin Pathway of the Complement System—Activation, Regulation, Disease Connections and Interplay with Other (Proteolytic) Systems

“…The MASP2 gene has two protein products, MASP-2 and MAp19 [9,43]. MASP-2 was the second protease component discovered after MASP-1 [6].…”

“…In the meantime, other, non-enzymatic components of the lectin pathway were also discovered. From both MASP1 and MASP2 genes, shorter N-terminal fragments lacking the catalytic domain (MAp19 and MAp44) are expressed via alternative splicing or polyadenylation [9,10]. The number of PRMs also has been increased by the discovery of ficolins (ficolin-1, -2 and -3) [11] and other collectins (CL-K1, CL-L1) [12].…”

Tinker, tailor, soldier, cell: the role of C-type lectins in the defense and promotion of disease

“…and colleagues demonstrated that MASP-1 was capable of cleaving factor XIII and fibrinogen ( Krarup et al, 2008 ) suggesting an alternative role for the enzyme potentially associated with coagulation ( Presanis et al, 2004 ; Krarup et al, 2007 ). In addition to MASP-1–3, there are also two non-enzymatic MASP splice variants; MAp44 ( Degn et al, 2009 ) and MAp19 ( Stover et al, 1999 ; Iwaki et al, 2006 ; Degn et al, 2011 ). Although the role of these splice variants remain debated, there is evidence that they may play a regulatory role for MASP activation ( Iwaki et al, 2006 ; Degn et al, 2009 ; Degn et al, 2013 ).…”

A komplementrendszer lektin útjának aktiválódása, szabályozása és a proteázok közvetlen sejtaktiváló hatása

“…A MASP-ok és az MBL-asszociált fehérjék (MAp19 és MAp44) -melyek nem rendelkezek szerin proteáz aktivitássalkét gén termékei. A MASP-1, a MASP-γ és a MAp44 a MASP1 gén, míg a MASP-β és a MAp19 a MASP2 gén alternatív splice variánsai (Degn et al, 2009;Skjoedt et al, 2010a;Stover et al, 1999;Takahashi et al, 1999). A MASP-ok doménszerkezete megegyezik a klasszikus út szerin proteázainak szerkezetével (C1s, C1r).…”

“…A MAp19 és a MAp44 nem rendelkezik proteáz funkcióval, azonban érdemes megemlíteni, hogy a MAp19 a MASP-β két első doménjét (CUB1 és EGF), a MAp44 pedig a MASP-1/3 első négy doménjét tartalmazza. Ezen kívül mindkét fehérjének van még egy Cterminális, pár aminosavból (4 illetve 17) álló szakasza, amely nem található meg a MASP-okban (Skjoedt et al, 2010a;Stover et al, 1999).…”