Disease relevance of MASP2

• The ficolin/P35-MASPs-sMAP complex that was bound to Salmonella typhimurium activated complement [1].
• Functional MASP2 single nucleotide polymorphism plays no role in psoriasis [2].
• To precisely determine their substrate specificity, human MASP-1 and MASP-2, and fragments from their catalytic regions were expressed using a baculovirus/insect cells system [3].
• EXPERIMENTAL DESIGN: MASP-2 concentrations were determined in serum from 605 patients collected before elective resection for primary colorectal cancer [4].
• MASP-2 expression in ESCCs was associated with late clinical stage (p = 0.009, O.R. = 3.430) and nodal metastasis (p = 0.001, O.R. = 4.520) [5].

High impact information on MASP2

• MASP-1, MAp19, and direct C3-cleaving activity are associated with smaller oligomers whereas MASP-3 is found together with MASP-2 on larger oligomers [6].
• MASP-3 downregulate the C4 and C2 cleaving activity of MASP-2 [6].
• Lectin Pathway of Bony Fish Complement: Identification of Two Homologs of the Mannose-Binding Lectin Associated with MASP2 in the Common Carp (Cyprinus carpio) [7].
• Molecular cloning and phylogenetic analysis revealed this C4-activating protease to be carp MASP2, indicating that MASP2 arose before the emergence of bony fish [7].
• Upon activation of the lectin pathway, MASP-2 cleaves C4 and C2 [8].

Chemical compound and disease context of MASP2

• The mannan-binding lectin pathway and lung disease in cystic fibrosis-dysfunction of mannan-binding lectin-associated serine protease 2 (MASP-2) may be a major modifier [9].

Biological context of MASP2

• The MASP1 gene is located on chromosome 3q27, the MASP2 gene on chromosome 1p36.23-31 [10].
• RESULTS: Ten percent of the donors and 11% of the recipients carried the MBL-low (O/O, LXA/O) genotypes; 7% of the donors and 3% of the recipients were heterozygous for the MASP2 Asp105Gly variant [11].
• A comparison of the MASP2 gene with the previously characterised C1s gene revealed identical positions of introns separating orthologous coding sequences, underlining the hypothesis that the C1s and MASP2 genes arose by exon shuffling from one ancestral gene [10].
• The stimulatory effects of IL-1beta on MASP1/3 and MASP2 gene expression were abolished by the simultaneous presence of IL-6 [12].
• Mammals and Xenopus possess two distinct MASPs, MASP1 and MASP2, with different substrate specificity [13].

Anatomical context of MASP2

• Assignment of the gene encoding mannan-binding lectin-associated serine protease 2 (MASP2) to human chromosome 1p36.3-->p36.2 by in situ hybridization and somatic cell hybrid analysis [14].
• Similarly, treatment of human endothelial cells with mouse anti-human CD59 IgM, MBL and MASP-2 activated and deposited C4 [15].
• Furthermore, a lamprey N-acetylglucosamine (GlcNAc)-binding lectin was identified as the orthlogue of mammalian C1q, and lamprey MASP is suggested as the prototype of MASP-2/C1r/C1s, indicating that the classical complement pathway arose as a part of the innate immune system [16].
• Such binding to the repeating sugar arrays on microbial surfaces may result in direct uptake by one or more collectin receptors on phagocyte surface or may trigger the activation of a pro-serine protease complex (MASP 1 and MASP 2) leading to cleavage of C4 and C2 of the classical complement pathway [17].

Associations of MASP2 with chemical compounds

• Complexes of MBL-MASP2 are able to activate the complement system in an Ab and C1-independent fashion after binding of the lectin to appropriate microbial sugar arrays [18].
• We have shown that the MASP2 gene encodes two gene products, the 76 kDa MASP-2 serine protease and a plasma protein of 19 kDa, termed MAp19 or sMAP [10].
• It is likely that human MASP1 is able to activate C3, while human MASP2 cleaves C4, although further functional studies are required to confirm this [19].
• On an anti-MASP-1 column, MASP-2 passed through the column in the presence of EDTA and high salt concentration, whereas MASP-1 was retained [20].
• Western blotting analysis showed the presence of MASP-1, MASP-2, MASP-3, and sMAP in H-ficolin preparations isolated from Cohn Fraction III [21].

Physical interactions of MASP2

• The lectin pathway of the complement system is activated when mannan-binding lectin (MBL) in complex with MBL-associated serine protease 2 (MASP-2) binds to carbohydrate structures on microorganisms [22].

Enzymatic interactions of MASP2

• We have demonstrated that MASP-2 is a C4 cleaving component of the MBL/MASP complex [23].

Regulatory relationships of MASP2

• MASP-2 is the protease responsible for activating C4 and C2 to generate the C3 convertase, C4bC2b [24].
• MBL also activates complement via the lectin pathway that requires a MBL-associated serine protease-2 (MASP-2) [25].

Other interactions of MASP2

• Isolated MASP-1 and MASP-2 exhibited proteolytic activities against C3 and C4, respectively [20].
• C1 inhibitor (C1 INH), an inhibitor for C1r and C1s, formed equimolar complexes with MASP-1 and MASP-2 and inhibited their proteolytic activities [20].
• We report here that ficolin/P35, a human serum ficolin, was found to copurify with MASPs and sMAP [1].
• Both enzymes cleaved C3i 10- to 20-fold faster, but still at only approximately 1% of the efficiency of MASP-2 cleavage of C2 [26].
• We suspect total MASP-2 dysfunction to be a major modifier of CF lung disease [9].

Analytical, diagnostic and therapeutic context of MASP2

• The three proteins and full-length MASP-1 and MASP-2 showed no interaction with each other as judged by gel filtration and surface plasmon resonance spectroscopy [27].
• To investigate the association of MASP-2 expression with esophageal tumorigenesis, its expression was analyzed in 51 primary ESCCs, 32 dysplasias, 21 histologically normal esophageal tissues and 6 adenocarcinomas by immunohistochemistry [5].
• No correlation to reduced lung function or need for lung transplantation was seen, either for MBL deficiency, MASP-2 gene mutation or reduced MBL pathway function [28].
• Southern blot and PCR analyses of rat genomic DNA indicate that as in humans, rat MASP-2 and MAp19 are encoded by a single structural gene [29].

References