Affinage

MASP1

Mannan-binding lectin serine protease 1 · UniProt P48740

Length
699 aa
Mass
79.2 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

The MASP1 gene encodes multiple products through alternative splicing and is the keystone initiator of the lectin complement pathway, generating MASP-1, MASP-3, and the non-catalytic regulator MAp44 (PMID:11485744, PMID:19917686). Upon assembly with the pattern-recognition collectins/ficolins—including MBL, ficolins, and CL-11—via Ca2+-dependent CUB1-EGF-CUB2 binding sites (PMID:18596036, PMID:20956340, PMID:23220946), MASP-1 self-activates with an autoactivation rate ~3000-fold higher than MASP-2 because its zymogen fluctuates into active-like conformations (PMID:23386610). Activated MASP-1 is the exclusive activator of MASP-2 in normal serum, transactivating it within MBL/ficolin co-complexes, and contributes ~60% of C2a generation for C3 convertase assembly (PMID:22691502, PMID:22966085, PMID:23785123); loss of MASP-1 abolishes lectin pathway activity in deficient mouse serum and human patients, rescued by reconstitution (PMID:18424734, PMID:22966085). The alternatively spliced MASP-3 product is the physiological maturase of pro-factor D in resting blood, thereby coupling the lectin and alternative pathways (PMID:27535802, PMID:31399515, PMID:28794230). A crystal structure of the MASP-1 catalytic region reveals a wide, trypsin-like substrate groove that explains its relaxed specificity (PMID:19564340), underlying a promiscuous protease role beyond complement: MASP-1 cleaves fibrinogen, factor XIII, prothrombin (at R271/R393) and TAFI to drive clot formation (PMID:18456010, PMID:22536427, PMID:26645987), releases bradykinin from high-molecular-weight kininogen (PMID:21625439), and activates endothelial cells through cleavage of PAR4 and PAR1 to trigger Ca2+/NF-κB/p38 MAPK signaling, IL-6/IL-8 production, E-selectin upregulation, and increased vascular permeability (PMID:19667088, PMID:24489848, PMID:31130964). MASP-1 is physiologically restrained by C1-inhibitor, and reduced MASP-1/C1-INH complexes track with hereditary angioedema (PMID:26371246). Loss-of-function mutations in the shared MASP1 exons cause 3MC syndrome, a neural crest–dependent developmental disorder (PMID:21035106, PMID:21258343).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 High

    Established that the MASP1/3 locus produces more than one protein, revealing MASP-3 as an alternatively spliced product with regulatory rather than purely activating function.

    Evidence Molecular cloning, MBL complex fractionation, and functional complement assays

    PMID:11485744

    Open questions at the time
    • Did not resolve the catalytic targets of MASP-3 itself
    • Stoichiometry of MASP-3 within native MBL oligomers not fully defined
  2. 2006 Medium

    Demonstrated cooperative roles of MASP-1 and MASP-2 in convertase assembly, addressing whether MASP-1 was functionally redundant.

    Evidence Depletion/reconstitution of complement-depleted human serum with C3b deposition readout

    PMID:17182967

    Open questions at the time
    • Did not establish whether MASP-1 acts upstream of MASP-2 or in parallel
    • Mechanism of MASP-3 inhibition unresolved
  3. 2008 High

    Defined the structural basis of collectin/ficolin recognition and confirmed in vivo that MASP-1 promotes MASP-2 activation, resolving how the initiation complex assembles and functions.

    Evidence CUB1-EGF-CUB2 crystal structure with mutagenesis/SPR, plus MASP1/3−/− mouse with recombinant reconstitution

    PMID:18424734 PMID:18596036

    Open questions at the time
    • Did not directly visualize a MASP-1/MASP-2 transactivation complex
    • Relative contribution of MASP-1 vs MASP-2 binding sites in mixed complexes unclear
  4. 2009 High

    Explained MASP-1's broad substrate specificity and confirmed PAR-mediated endothelial signaling, distinguishing it mechanistically from the narrow-specificity complement proteases.

    Evidence Catalytic-region crystal structure at 2.55 Å and PAR4 cleavage/Ca2+/NF-κB/p38 signaling assays in HUVECs

    PMID:19564340 PMID:19667088

    Open questions at the time
    • Did not identify the full physiological substrate repertoire
    • In vivo relevance of endothelial PAR4 signaling not tested
  5. 2009 High

    Identified MAp44 as a fourth MASP1/3 splice product acting as a competitive inhibitor of the lectin pathway, establishing intragenic regulatory control.

    Evidence SPR binding kinetics, ELISA, and complement inhibition assays

    PMID:19917686

    Open questions at the time
    • In vivo concentration-dependent regulation not quantified
    • Tissue-specific splice product ratios unaddressed
  6. 2012 High

    Proved MASP-1 is the exclusive activator of MASP-2 in normal serum and an essential initiator, settling the hierarchy of lectin pathway protease activation.

    Evidence Monospecific MASP-1/MASP-2 inhibitor proteins and patient serum reconstitution with co-complex ELISA, supported by Michaelis-complex crystal structures

    PMID:22511776 PMID:22691502 PMID:22966085

    Open questions at the time
    • Quantitative kinetics of transactivation within native complexes not fully defined
    • Whether all MBL/ficolin complexes carry both proteases unresolved
  7. 2013 High

    Quantified MASP-1's exceptionally high zymogen autoactivation and showed it cleaves both MASP-2 and MASP-3 proenzymes, explaining how the pathway is triggered without an upstream activator.

    Evidence Rate-constant measurements with zymogen/active-site mutants and proenzyme MASP-1 crystal structure at 2.5 Å

    PMID:23386610

    Open questions at the time
    • Trigger that converts surface binding into autoactivation in vivo not defined
    • Conformational dynamics modeled crystallographically rather than in solution
  8. 2013 Medium

    Clarified the architecture of transactivation by showing MASP-1/MASP-2 co-complexes form only via MBL/ficolin scaffolds and that MAp44 disrupts these complexes.

    Evidence Gel filtration, ELISA co-complex detection, and complement activation assays

    PMID:23785123

    Open questions at the time
    • Single-lab biochemical detection without structural confirmation
    • Direct vs scaffold-mediated heterodimer contributions partly resolved only by later fragment studies
  9. 2014 Medium

    Mapped MASP-1/MASP-2 and MASP-1/MASP-3 dimerization behavior through CUB1-EGF-CUB2 fragments, defining how subunit pairing is governed by Ca2+.

    Evidence Size-exclusion chromatography, native PAGE, and EDTA dissociation/re-association with recombinant fragments

    PMID:24424083

    Open questions at the time
    • Used isolated fragments rather than full-length proteins
    • Physiological relevance of heterodimers vs homodimers in serum not established
  10. 2014 High

    Showed native serum MBL-MASP complexes activate endothelium and that this requires MASP-1 catalytic activity, anchoring the signaling role to physiological complexes.

    Evidence Ca2+ signaling assays in HUVECs comparing native complexes, recombinant fragments, and zymogen mutant; plus cytokine/chemotaxis assays

    PMID:24472859 PMID:24489848

    Open questions at the time
    • In vivo endothelial activation by MASP-1 not demonstrated
    • Receptor(s) mediating cytokine induction not fully resolved in these studies
  11. 2008 High

    Demonstrated MASP-1 cross-talk with coagulation by cleaving fibrinogen and factor XIII at thrombin-like sites, opening the link between complement and hemostasis.

    Evidence In vitro cleavage assays, SDS-PAGE, N-terminal sequencing with thrombin comparison

    PMID:18456010

    Open questions at the time
    • Slow turnover (~650-fold lower than thrombin) leaves physiological significance to be weighted
    • In vivo contribution to clotting not addressed here
  12. 2011 High

    Established MASP-1 as a bradykinin-generating protease via kininogen cleavage, connecting it to vascular permeability and inflammation.

    Evidence Proteomics, SDS-PAGE, HPLC bradykinin detection, and kinetics with C1-inhibitor control

    PMID:21625439

    Open questions at the time
    • In vivo bradykinin release by MASP-1 not demonstrated
    • Relative contribution versus kallikrein not quantified
  13. 2015 High

    Defined the prothrombin cleavage mechanism, showing MASP-1 activates prothrombin via two parallel cleavage routes generating alternative thrombin species.

    Evidence Arginine-to-glutamine prothrombin mutants, N-terminal sequencing, and thrombelastography (also 2012/2014 plasma and purified-system clot assays)

    PMID:22536427 PMID:25745807 PMID:26645987

    Open questions at the time
    • Physiological flux through MASP-1-driven prothrombin activation in vivo not quantified
    • Interplay with TAFI/clot-lysis effects not fully integrated
  14. 2016 High

    Identified MASP-3 as the exclusive activator of pro-factor D in resting blood, establishing a direct molecular bridge between the lectin and alternative complement pathways.

    Evidence Evolved monospecific MASP inhibitors in resting blood with pro-FD activation assays and kinetics (with companion 2015 plasma assays)

    PMID:26673137 PMID:27535802

    Open questions at the time
    • Whether residual MASP-3-independent FD maturation contributes was clarified only later
    • Spatial site of pro-FD activation in vivo unknown
  15. 2017 High

    Linked 3MC-associated MASP-3 mutations to loss of factor D maturase activity, explaining the alternative-pathway defect while revealing MASP-3-independent maturation also exists.

    Evidence Isoelectric focusing of FD variants, mutant enzyme characterization, MASP-3-depleted serum, patient sera, and KO mice

    PMID:28794230

    Open questions at the time
    • Identity of the MASP-3-independent FD maturase not determined
    • How 3MC craniofacial phenotype relates to FD maturation defect unclear
  16. 2018 Medium

    Showed MASP-1 contributes to surface-specific alternative pathway activation (LPS but not zymosan) and to clot formation under flow, extending its role into pathogen-context and physiological hemostasis.

    Evidence Specific MASP-1 inhibitors (SGMI-1 and others) in AP assays and a microvascular endothelialized whole-blood clot model

    PMID:29324883 PMID:29475986

    Open questions at the time
    • Molecular basis of the LPS-specific MASP-1 requirement not elucidated
    • Single-lab flow models await independent replication
  17. 2019 High

    Defined PAR1-dependent endothelial permeability signaling and confirmed in monospecific KO mice that MASP-1 (not MASP-3) drives lectin pathway activation while MASP-3 drives FD maturation, cleanly separating the two splice products' physiological roles.

    Evidence Impedance/permeability/Ca2+/Rho-kinase assays in HUVECs and monospecific MASP-1-KO and MASP-3-KO mice with pathway activity readouts

    PMID:31130964 PMID:31399515

    Open questions at the time
    • In vivo permeability consequences of MASP-1 PAR1 signaling not tested in the KO mice
    • Crosstalk between bradykinin-receptor upregulation and PAR signaling unresolved
  18. 2022 Medium

    Extended MASP-1 biology to organ fibrosis, showing hepatocyte-derived MASP1 in extracellular vesicles activates hepatic stellate cells via p38 MAPK/ATF2 to promote liver fibrogenesis.

    Evidence CCl4/NASH mouse models, EV proteomics, siRNA knockdown, and p38 MAPK signaling assays

    PMID:35849032

    Open questions at the time
    • Whether catalytic activity of MASP1 is required for HSC activation not fully isolated
    • Single-lab study awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse non-complement substrates (coagulation factors, kininogen, PAR receptors) are integrated in vivo, and the identity of the MASP-3-independent factor D maturase, remain unresolved.
  • No in vivo quantification of MASP-1's relative contribution to coagulation versus dedicated coagulation proteases
  • Identity of MASP-3-independent FD maturase unknown
  • Mechanism coupling MASP-1 endothelial signaling to systemic vascular phenotypes undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016787 hydrolase activity 5 GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 5 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-109582 Hemostasis 4 R-HSA-162582 Signal Transduction 4
Partners
C2CFDCOLEC11F2FCN1MASP2MBL2SERPING1
Complex memberships
CL-11 (collectin-11) initiation complexMASP-1/C1-inhibitor complexMBL-MASP lectin pathway initiation complexficolin-MASP complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MASP-3 is generated through alternative splicing of the MASP-1/3 gene and associates with larger MBL oligomers together with MASP-2, while MASP-1 associates with smaller oligomers. MASP-3 downregulates the C4 and C2 cleaving activity of MASP-2. Molecular cloning, MBL complex fractionation, functional complement assays Immunity High 11485744
2009 MAp44, a fourth product of the MASP1/3 gene (sharing CUB1-EGF-CUB2-CCP1 domains with MASP-1 and MASP-3 but with a unique 17 aa C-terminus), circulates in Ca2+-dependent complexes with MBL and ficolins (KD ~0.6 nM for MBL) and competes with MASP-2 for binding to MBL and ficolins, thereby inhibiting complement activation. Surface plasmon resonance, ELISA, complement activation inhibition assays Journal of immunology High 19917686
2012 In normal human serum, MASP-1 is the exclusive activator of MASP-2; MASP-2 autoactivation is strictly dependent on prior activation by MASP-1, and MASP-1 inhibition prevents MASP-2 autoactivation. Additionally, MASP-1 contributes ~60% of C2a formation responsible for C3 convertase assembly. Monospecific inhibitor proteins against MASP-1 and MASP-2 used in functional lectin pathway assays with normal human serum Proceedings of the National Academy of Sciences of the United States of America High 22691502
2008 MASP-1 contributes to lectin pathway activation, primarily by promoting MASP-2 activation. MASP-1/3-deficient mouse serum shows significantly reduced C4 and C3 deposition on mannan, which is restored by reconstitution with recombinant MASP-1. MASP-1 promotes MASP-2 activation in deficient serum. Gene-targeted MASP1/3−/− mouse model, serum complement activity assays, reconstitution with recombinant MASP-1 Journal of immunology High 18424734
2012 In a MASP-1/MASP-3-deficient human patient (nonsense mutation in common MASP1 exon), the lectin pathway is nonfunctional but the alternative pathway functions normally. Reconstitution with MASP-1 restores lectin pathway activity through direct activation of MASP-2. MASP-1 and MASP-2 can co-associate in the same MBL complex (co-complexes found in serum), enabling transactivation. Patient serum studies, complement pathway activity assays, reconstitution, ELISA co-complex detection Journal of immunology High 22966085
2009 Crystal structure of active MASP-1 catalytic region resolved at 2.55 Å reveals a wide substrate-binding groove resembling trypsin rather than early complement proteases, an unusual internal salt bridge between S1 Asp189 and Arg224, and a very long 60-loop, explaining MASP-1's broad/relaxed substrate specificity. X-ray crystallography (2.55 Å resolution) Journal of immunology High 19564340
2016 MASP-3 is the exclusive activator of pro-factor D in resting blood. Using evolved monospecific MASP-1 and MASP-3 inhibitors, neither MASP-1 nor MASP-2 activates pro-FD in resting blood, but MASP-3 inhibition abolishes pro-FD maturation, demonstrating a fundamental link between the lectin and alternative complement pathways. Evolved monospecific MASP inhibitors applied to resting blood; pro-FD activation assays; in vitro kinetics Scientific reports High 27535802
2009 MASP-1 activates Ca2+ signaling, NF-κB, and p38 MAPK pathways in human endothelial cells (HUVECs) through cleavage of PAR4 (protease-activated receptor 4). Activation requires proteolytic activity of MASP-1; MASP-2 has no such effect. Membrane-bound intact PAR4 decreases after MASP-1 treatment. Cell signaling assays (Ca2+ imaging, western blot for NF-κB/p38 MAPK), synthetic PAR peptide substrate cleavage assays, mRNA quantification, flow cytometry Journal of immunology High 19667088
2008 Crystal structure of the CUB1-EGF-CUB2 domain of human MASP-1/3 resolved at 2.3 Å. The structure shows a head-to-tail homodimer stabilized by hydrophobic interactions and Ca2+ ions. Point mutagenesis of 27 residues in MASP-3 identified two homologous binding sites (on CUB1 and CUB2) for MBL and ficolins, located near Ca2+-binding sites, involving a major electrostatic interaction between acidic Ca2+ ligands of MASP-1/3 and a conserved lysine of MBL. X-ray crystallography (2.3 Å), site-directed mutagenesis, surface plasmon resonance The Journal of biological chemistry High 18596036
2013 MASP-1 autoactivation rate is ~3000-fold higher than MASP-2 autoactivation; both activated and zymogen MASP-1 cleave proenzyme MASP-2 efficiently; MASP-1 also cleaves MASP-3 proenzyme. Crystal structure of proenzyme MASP-1 R448Q at 2.5 Å shows zymogen MASP-1 fluctuates between inactive and active-like conformations, explaining its unusually high zymogen activity. Rate constant measurements with zymogen and active-site mutant recombinant proteins, X-ray crystallography (2.5 Å), kinetic modeling The Journal of biological chemistry High 23386610
2012 MASP-1 and MASP-2 are both essential for lectin pathway activation. A monospecific MASP-1 inhibitor completely blocks lectin pathway activation. Crystal structures of Michaelis-like complexes of MASP-1 and MASP-2 with substrate-like inhibitors resolved at 1.28 Å (MASP-2) reveal significant plasticity of MASP-2. Evolved monospecific inhibitors, complement activation assays, X-ray crystallography The Journal of biological chemistry High 22511776
2004 MASP-1 cleaves fluorescent amide substrates with preference for Phe-Gly-Arg-AMC (rate 16.8 nmol/min/µg). C1 inhibitor inhibits both MASP-1 and MASP-2 (though complexes are unstable at alkaline pH). The thrombin inhibitor boroMpg inhibits MASP-1 but not MASP-2, and antithrombin III with heparin inhibits both MASPs. In vitro enzyme assays with fluorescent amide substrates, inhibitor profiling Molecular immunology High 14725788
2008 MASP-1 cleaves factor XIII A-chain and fibrinogen beta-chain at identical sites to thrombin, but with ~650-fold lower turnover rate. MASP-1 cleavage of fibrinogen releases proinflammatory fibrinopeptide B (not fibrinopeptide A as thrombin does for the alpha-chain). MASP-1 can drive formation of cross-linked fibrinogen. In vitro cleavage assays, SDS-PAGE, N-terminal sequencing, comparison with thrombin Biochimica et biophysica acta High 18456010
2011 MASP-1 cleaves high-molecular-weight kininogen (HK) to release bradykinin (BK). MASP-2 also cleaves HK but cannot release BK. Catalytic efficiency of HK cleavage by recombinant MASP-1 is ~4.0×10² M⁻¹s⁻¹. C1-inhibitor prevents HK cleavage by MASP-1. Differential gel electrophoresis proteomics, SDS-PAGE, HPLC for BK detection, kinetic measurements PloS one High 21625439
2012 MASP-1 activates factor XIII, prothrombin (generating F1+2 fragments), fibrinogen (generating fibrinopeptide A via thrombin), and TAFI in citrated plasma and purified systems. MASP-1 induces clot formation and affects fibrin clot structure in NCP; it prolongs clot lysis. MASP-1-induced fibrin formation is thrombin-dependent but MASP-1 directly activates prothrombin. FXIII incorporation assay, specific cleavage product assays, turbidimetric clot assay, scanning electron microscopy PloS one High 22536427
2015 MASP-1 cleaves prothrombin at three sites (R155, R271, R393) identified by N-terminal sequencing, promotes clot formation in whole blood and platelet-poor plasma (measured by thrombelastography), and shortens clotting time. MASP-1-induced clotting requires prothrombin in a purified system. SDS-PAGE, N-terminal sequencing, thrombelastography, purified system reconstitution Molecular immunology High 25745807
2015 MASP-1 activates prothrombin via two simultaneous pathways (cleaving R271 or R393 first), generating active alternative thrombin species. Both R393 and R320 are required for prothrombin activation by MASP-1; R155 is not an important cleavage site. Arginine-to-glutamine prothrombin mutants, SDS-PAGE, N-terminal sequencing, thrombelastography PloS one High 26645987
2014 MASP-1 induces IL-6 and IL-8 (but not IL-1α, IL-1ra, TNFα, MCP-1) production in HUVECs through the p38-MAPK pathway, and the conditioned medium triggers neutrophil chemotaxis. Cytokine ELISA, p38-MAPK pathway inhibition, neutrophil chemotaxis assay PloS one High 24489848
2016 MASP-1 activates endothelial cells to up-regulate E-selectin expression and decrease ICAM-2, resulting in increased adhesion between endothelial cells and neutrophil granulocytes. ICAM-1, VCAM-1, and P-selectin remain unchanged. Flow cytometry for adhesion molecules on HUVECs, adhesion assay with differentiated PLB-985 cells Molecular immunology Medium 27219453
2019 MASP-1 increases endothelial paracellular permeability through PAR1-mediated intracellular Ca2+ mobilization, Rho-kinase activation, myosin light chain phosphorylation, cytoskeletal actin rearrangement, and disruption of interendothelial junctions. MASP-1 also up-regulates bradykinin B2 receptor expression in HUVECs. Real-time electric impedance sensing, XperT permeability assay, Ca2+ imaging, Rho-kinase inhibition, whole-transcriptome microarray Frontiers in immunology High 31130964
2014 Serum MASP-1 in complex with MBL (native lectin pathway complexes) activates endothelial cells (Ca2+ signaling). Among MBL-associated components, only MASP-1 triggers this response; MASP-2, MASP-3, non-enzymatic domains of MASP-1/MASP-2, and zymogen MASP-1 mutant are all ineffective, indicating proteolytic activity of MASP-1 is required. Ca2+ signaling assay in HUVECs with native serum MBL-MASP complexes and recombinant fragments/mutants Molecular immunology High 24472859
2011 MASP-1 mutations in the MASP1 gene (shared exons encoding both MASP-1 and MASP-3, or isoforms affecting only MASP-3) cause 3MC syndrome (Carnevale, Malpuech, Michels, Mingarelli). A missense mutation p.G687R and a nonsense mutation p.W290X both cosegregate with the syndrome phenotype in consanguineous families. Exome sequencing, Sanger sequencing, homozygosity mapping, cosegregation analysis American journal of human genetics Medium 21035106
2011 COLEC11 and MASP1 mutations cause 3MC syndrome. CL-K1 (encoded by COLEC11) serves as a guidance cue for neural crest cell migration; zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities, demonstrating a role for lectin complement pathway factors in neural crest-dependent developmental processes. Human genetics (mutation identification), zebrafish morpholino knockdown, craniofacial phenotype analysis, neural crest cell migration assay Nature genetics Medium 21258343
2013 MASP-1 and MASP-2 do not directly form heterodimers, but addition of MBL or ficolins enables formation of MASP-1/MASP-2 co-complexes in serum. These co-complexes have a functional role in activating complement; MAp44 inhibits complement not only by displacing MASP-2 from MBL/ficolins but by disrupting MASP-1/MASP-2 co-complexes and impairing transactivation. Gel filtration, ELISA co-complex detection in serum, functional complement activation assays with defined MBL/ficolin complexes Journal of immunology Medium 23785123
2014 MASP-1 and MASP-2 can form heterodimers via their CUB1-EGF-CUB2 regions after Ca2+-mediated dissociation and re-association. Heterodimer formation between MASP-1 and MASP-3 subunits occurs even in the presence of Ca2+. Both MASP-1 and MASP-2 form tight Ca2+-dependent homodimers. Size exclusion chromatography, native PAGE, EDTA dissociation/re-association kinetics with recombinant CUB1-EGF-CUB2 fragments Molecular immunology Medium 24424083
2015 MASP-1 and MASP-2 do not activate pro-factor D in resting human plasma/serum. MASP-3 is the most likely physiological activator of pro-FD; selective MASP-1 and MASP-2 inhibitors do not reduce pro-FD activation, whereas a high concentration MASP-2 inhibitor (which also weakly inhibits MASP-3) slows activation, and added recombinant MASP-3 reduces pro-FD half-life. Fluorescently labeled pro-FD activation assay in serum/plasma, selective MASP inhibitors, kinetic measurements with purified enzymes Journal of immunology High 26673137
2019 MASP-3, but not MASP-1, activates pro-factor D under physiological conditions in mice. Mice monospecifically deficient in MASP-1 lack lectin pathway activity but have normal alternative pathway with active FD, whereas MASP-3-deficient mice lack alternative pathway activity with zymogenic FD present. MASP-3 circulates predominantly as an active form. Monospecific MASP-1-KO and MASP-3-KO mouse generation, complement pathway activity assays, FD zymogen detection Journal of immunology High 31399515
2017 3MC-associated MASP-3 mutations all yield enzymatically inactive MASP-3 protein. In MASP-3-depleted human serum, sera from 3MC patients, and Masp1/3−/− mice, lack of enzymatically active MASP-3 compromises pro-FD-to-FD conversion, confirming MASP-3 as an important maturase of factor D in the alternative pathway. 3MC patients contain predominantly pro-FD but also detectable mature FD, indicating MASP-3-independent maturation also occurs. Isoelectric focusing of endogenous FD variants, enzymatic characterization of mutant MASP-3 proteins, MASP-3-depleted human serum assays, patient sera, KO mice Journal of immunology High 28794230
2018 MASP-1 is essential for LPS-induced alternative pathway (AP) activation but has little effect on zymosan-induced AP activation. MASP-1 inhibition (by SGMI-1 and other inhibitors with different mechanisms) prevents AP activation on LPS surfaces and attenuates already-initiated AP activity. Specific MASP-1 inhibitors (SGMI-1 and others) in AP complement activation assays on LPS and zymosan surfaces Journal of immunology Medium 29475986
2010 CL-11 (collectin-11) copurifies with and interacts with MASP-1 and/or MASP-3 in plasma as demonstrated by ELISA. CL-11 forms the fifth lectin pathway initiation complex with MASP-1, MASP-2, MASP-3, and MAP-1; complex formation between recombinant CL-11 and MASP-2 on Candida albicans leads to C4b deposition. Copurification, ELISA, complement deposition assays on C. albicans Journal of immunology Medium 20956340 23220946
2006 MASP-1 cooperates with MASP-2 in generating C3 convertase through the MBL pathway. In MASP-1/2/3-depleted serum, reconstitution with both MASP-1 and MASP-2 has a synergistic effect on C3b deposition on mannan; MASP-3 inhibits this activity. No C3b deposition occurs with C2- or C4-depleted serum; factor B depletion has no effect. Depletion and reconstitution experiments with complement-depleted human serum, C3b deposition assay International immunology Medium 17182967
2010 Phage display-evolved peptide SFMI-1 inhibits MASP-1 (KI 65 nM) and MASP-2 (KI 1030 nM); SFMI-2 inhibits only MASP-2 (KI 180 nM). SFMI-1 is more effective than SFMI-2 at preventing C3 and C4 deposition when zymogen MASPs are present, confirming MASP-1's crucial role in initiation by activating MASP-2. Phage display peptide selection, kinetic inhibition measurements, C3/C4 deposition assays with zymogen MASPs Journal of immunology Medium 20817870
2015 MASP-1/C1-INH complexes circulate in normal human blood. MASP-1 levels and MASP-1/C1-INH complex levels are significantly reduced in hereditary angioedema (HAE) patients (p<0.0001), correlating with C4 consumption and attack frequency, indicating MASP-1 is physiologically inhibited by C1-inhibitor and may contribute to HAE pathophysiology. ELISA for MASP-1 and MASP-1/C1-INH complexes in 128 HAE patients and 100 controls; correlation analysis Journal of immunology Medium 26371246
2018 MASP-1 enhances fibrin clot formation in a microvascular whole blood flow model. Addition of recombinant active MASP-1 accelerates fibrin clot formation; MASP-1-specific inhibitor SGMI-1 delays clot formation. Complement activation by zymosan increases clot formation, partially reversed by classical pathway inhibitor and almost abolished by SGMI-1 combined with it. Microfluidic endothelialized microchannel clot formation assay with real-time confocal microscopy, pathway-specific inhibitors PloS one Medium 29324883
2022 ARRB1 upregulates MASP1 expression in hepatocytes and promotes release of MASP1-enriched small extracellular vesicles via regulation of the autophagic-lysosomal/multivesicular body pathway and Rab27A activation. Hepatocyte-derived MASP1 activates hepatic stellate cells (HSCs) through p38 MAPK/ATF2 signaling to promote liver fibrogenesis. CCl4/NASH mouse models, primary cell isolation, small EV purification, proteomics, siRNA knockdown, p38 MAPK signaling assays, in vivo MASP1 overexpression Hepatology Medium 35849032
2020 C-reactive protein (CRP) binds monosodium urate crystals and recruits complement proteases C1 (C1q, C1r, C1s) and MASP-1, providing a pattern recognition mechanism linking MSU crystal recognition to complement activation. MSU crystal pulldown/purification from human body fluids, mass spectrometry identification, depletion of CRP from serum Scientific reports Low 32286427
1995 The human CRARF gene (encoding P100, later identified as MASP-1) was mapped by FISH to chromosome 3q27-q28, and the mouse homolog (Crarf) to chromosome 16B2-B3. Fluorescence in situ hybridization (FISH) on R-banded metaphase chromosomes Genomics Medium 7759119

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 278 11485744
2011 Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nature genetics 197 21258343
2008 Poly(ethylene glycol)s generate complement activation products in human serum through increased alternative pathway turnover and a MASP-2-dependent process. Molecular immunology 177 18849076
2010 Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma collectin with microbial-binding activity. Journal of immunology (Baltimore, Md. : 1950) 170 20956340
2012 Revised mechanism of complement lectin-pathway activation revealing the role of serine protease MASP-1 as the exclusive activator of MASP-2. Proceedings of the National Academy of Sciences of the United States of America 164 22691502
2009 MAp44, a human protein associated with pattern recognition molecules of the complement system and regulating the lectin pathway of complement activation. Journal of immunology (Baltimore, Md. : 1950) 138 19917686
2020 Safety, Tolerability and Efficacy of Narsoplimab, a Novel MASP-2 Inhibitor for the Treatment of IgA Nephropathy. Kidney international reports 130 33163724
2008 Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway. Journal of immunology (Baltimore, Md. : 1950) 127 18424734
2012 Mannan-binding lectin-associated serine protease (MASP)-1 is crucial for lectin pathway activation in human serum, whereas neither MASP-1 nor MASP-3 is required for alternative pathway function. Journal of immunology (Baltimore, Md. : 1950) 116 22966085
2004 Differential substrate and inhibitor profiles for human MASP-1 and MASP-2. Molecular immunology 114 14725788
2016 MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked. Scientific reports 108 27535802
2009 Complement protease MASP-1 activates human endothelial cells: PAR4 activation is a link between complement and endothelial function. Journal of immunology (Baltimore, Md. : 1950) 108 19667088
2010 MASP1 mutations in patients with facial, umbilical, coccygeal, and auditory findings of Carnevale, Malpuech, OSA, and Michels syndromes. American journal of human genetics 103 21035106
2022 Highly pathogenic coronavirus N protein aggravates inflammation by MASP-2-mediated lectin complement pathway overactivation. Signal transduction and targeted therapy 101 36100602
2009 MASP-1, a promiscuous complement protease: structure of its catalytic region reveals the basis of its broad specificity. Journal of immunology (Baltimore, Md. : 1950) 98 19564340
2012 Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. PloS one 96 22536427
2012 Collectin-11/MASP complex formation triggers activation of the lectin complement pathway--the fifth lectin pathway initiation complex. Journal of innate immunity 96 23220946
1998 Two lineages of mannose-binding lectin-associated serine protease (MASP) in vertebrates. Journal of immunology (Baltimore, Md. : 1950) 94 9794427
2008 The action of MBL-associated serine protease 1 (MASP1) on factor XIII and fibrinogen. Biochimica et biophysica acta 92 18456010
2011 Cleavage of kininogen and subsequent bradykinin release by the complement component: mannose-binding lectin-associated serine protease (MASP)-1. PloS one 91 21625439
2011 Serum concentrations of lectin-pathway components in healthy neonates, children and adults: mannan-binding lectin (MBL), M-, L-, and H-ficolin, and MBL-associated serine protease-2 (MASP-2). Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 88 21226765
2009 Multi-component complement system of Cnidaria: C3, Bf, and MASP genes expressed in the endodermal tissues of a sea anemone, Nematostella vectensis. Immunobiology 82 19195737
2014 Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation. Molecular immunology 81 24935208
2010 Biological variations of MASP-3 and MAp44, two splice products of the MASP1 gene involved in regulation of the complement system. Journal of immunological methods 81 20673767
2017 Progressive IgA Nephropathy Is Associated With Low Circulating Mannan-Binding Lectin-Associated Serine Protease-3 (MASP-3) and Increased Glomerular Factor H-Related Protein-5 (FHR5) Deposition. Kidney international reports 80 29725647
2022 Hepatocyte-derived MASP1-enriched small extracellular vesicles activate HSCs to promote liver fibrosis. Hepatology (Baltimore, Md.) 76 35849032
2006 Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway. International immunology 73 17182967
2003 Origin of mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 involved in the lectin complement pathway traced back to the invertebrate, amphioxus. Journal of immunology (Baltimore, Md. : 1950) 72 12707349
2016 MASP1, THBS1, GPLD1 and ApoA-IV are novel biomarkers associated with prediabetes: the KORA F4 study. Diabetologia 69 27344311
2012 Monospecific inhibitors show that both mannan-binding lectin-associated serine protease-1 (MASP-1) and -2 Are essential for lectin pathway activation and reveal structural plasticity of MASP-2. The Journal of biological chemistry 69 22511776
2012 Mannan-binding lectin (MBL)-associated serine protease-1 (MASP-1), a serine protease associated with humoral pattern-recognition molecules: normal and acute-phase levels in serum and stoichiometry of lectin pathway components. Clinical and experimental immunology 69 22670777
2008 Crystal structure of the CUB1-EGF-CUB2 domain of human MASP-1/3 and identification of its interaction sites with mannan-binding lectin and ficolins. The Journal of biological chemistry 65 18596036
2007 Elucidation of the substrate specificity of the MASP-2 protease of the lectin complement pathway and identification of the enzyme as a major physiological target of the serpin, C1-inhibitor. Molecular immunology 65 17709141
2010 Selective inhibition of the lectin pathway of complement with phage display selected peptides against mannose-binding lectin-associated serine protease (MASP)-1 and -2: significant contribution of MASP-1 to lectin pathway activation. Journal of immunology (Baltimore, Md. : 1950) 64 20817870
2009 Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2-q29 in squamous cell carcinoma of the lung. BMC cancer 63 19607727
2004 The structure of MBL-associated serine protease-2 reveals that identical substrate specificities of C1s and MASP-2 are realized through different sets of enzyme-substrate interactions. Journal of molecular biology 62 15364579
2013 Quantitative characterization of the activation steps of mannan-binding lectin (MBL)-associated serine proteases (MASPs) points to the central role of MASP-1 in the initiation of the complement lectin pathway. The Journal of biological chemistry 58 23386610
2011 Sequence-structure correlations in silk: Poly-Ala repeat of N. clavipes MaSp1 is naturally optimized at a critical length scale. Journal of the mechanical behavior of biomedical materials 57 22340682
2007 Multiple recombining loci encode MaSp1, the primary constituent of dragline silk, in widow spiders (Latrodectus: Theridiidae). Molecular biology and evolution 52 18048404
2015 MASP-1 of the complement system promotes clotting via prothrombin activation. Molecular immunology 51 25745807
2013 Co-complexes of MASP-1 and MASP-2 associated with the soluble pattern-recognition molecules drive lectin pathway activation in a manner inhibitable by MAp44. Journal of immunology (Baltimore, Md. : 1950) 50 23785123
2016 Mannan binding lectin-associated serine protease-2 (MASP-2) critically contributes to post-ischemic brain injury independent of MASP-1. Journal of neuroinflammation 48 27577570
2007 Molecular interactions between MASP-2, C4, and C2 and their activation fragments leading to complement activation via the lectin pathway. The Journal of biological chemistry 48 17204478
2006 The mannan-binding lectin pathway and lung disease in cystic fibrosis--disfunction of mannan-binding lectin-associated serine protease 2 (MASP-2) may be a major modifier. Clinical immunology (Orlando, Fla.) 48 17045845
2017 Analysis of Factor D Isoforms in Malpuech-Michels-Mingarelli-Carnevale Patients Highlights the Role of MASP-3 as a Maturase in the Alternative Pathway of Complement. Journal of immunology (Baltimore, Md. : 1950) 47 28794230
2005 Carbohydrate-binding specificities of mouse ficolin A, a splicing variant of ficolin A and ficolin B and their complex formation with MASP-2 and sMAP. Immunogenetics 47 16328467
2003 Expression of H-ficolin/Hakata antigen, mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 by human glioma cell line T98G. International immunology 46 12502731
2014 Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) in women with malignant and benign ovarian tumours. Cancer immunology, immunotherapy : CII 45 25038892
2015 MASP-1 and MASP-2 Do Not Activate Pro-Factor D in Resting Human Blood, whereas MASP-3 Is a Potential Activator: Kinetic Analysis Involving Specific MASP-1 and MASP-2 Inhibitors. Journal of immunology (Baltimore, Md. : 1950) 43 26673137
2014 MASP-1 induces a unique cytokine pattern in endothelial cells: a novel link between complement system and neutrophil granulocytes. PloS one 43 24489848
2019 Cutting Edge: Role of MASP-3 in the Physiological Activation of Factor D of the Alternative Complement Pathway. Journal of immunology (Baltimore, Md. : 1950) 41 31399515
2007 Role of MBL-associated serine protease (MASP) on activation of the lectin complement pathway. Advances in experimental medicine and biology 40 17892207
2015 Novel MASP1 mutations are associated with an expanded phenotype in 3MC1 syndrome. Orphanet journal of rare diseases 38 26419238
1998 MASP1 (MBL-associated serine protease 1). Immunobiology 38 9777417
2015 Plasma levels of mannan-binding lectin-associated serine proteases MASP-1 and MASP-2 are elevated in type 1 diabetes and correlate with glycaemic control. Clinical and experimental immunology 36 25533914
2015 The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema. Journal of immunology (Baltimore, Md. : 1950) 36 26371246
2001 The human gene for mannan-binding lectin-associated serine protease-2 (MASP-2), the effector component of the lectin route of complement activation, is part of a tightly linked gene cluster on chromosome 1p36.2-3. Genes and immunity 35 11426320
2019 MASP-1 Increases Endothelial Permeability. Frontiers in immunology 33 31130964
2014 Essential role for the lectin pathway in collagen antibody-induced arthritis revealed through use of adenovirus programming complement inhibitor MAp44 expression. Journal of immunology (Baltimore, Md. : 1950) 33 25070856
2014 TFPI inhibits lectin pathway of complement activation by direct interaction with MASP-2. European journal of immunology 33 25359215
2005 Functional characterization of complement proteases C1s/mannan-binding lectin-associated serine protease-2 (MASP-2) chimeras reveals the higher C4 recognition efficacy of the MASP-2 complement control protein modules. The Journal of biological chemistry 33 16227207
2022 In-depth mapping of protein localizations in whole tissue by micro-scaffold assisted spatial proteomics (MASP). Nature communications 32 36517484
2014 Impact of passive smoking, cooking with solid fuel exposure, and MBL/MASP-2 gene polymorphism upon susceptibility to tuberculosis. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 32 25312983
2015 Impact of MBL and MASP-2 gene polymorphism and its interaction on susceptibility to tuberculosis. BMC infectious diseases 31 25887173
2016 Complement MASP-1 enhances adhesion between endothelial cells and neutrophils by up-regulating E-selectin expression. Molecular immunology 30 27219453
2016 CsMAP34, a teleost MAP with dual role: A promoter of MASP-assisted complement activation and a regulator of immune cell activity. Scientific reports 29 28008939
2022 Distinction of early complement classical and lectin pathway activation via quantification of C1s/C1-INH and MASP-1/C1-INH complexes using novel ELISAs. Frontiers in immunology 27 36420270
2018 MASP-1 of the complement system enhances clot formation in a microvascular whole blood flow model. PloS one 27 29324883
2014 C3 dysregulation due to factor H deficiency is mannan-binding lectin-associated serine proteases (MASP)-1 and MASP-3 independent in vivo. Clinical and experimental immunology 27 24279761
2009 Mannan-binding lectin-associated serine protease-2 (MASP-2) in a large cohort of neonates and its clinical associations. Molecular immunology 27 19307021
1998 MASP-2, the C3 convertase generating protease of the MBLectin complement activating pathway. Immunobiology 27 9777418
1999 The rat and mouse homologues of MASP-2 and MAp19, components of the lectin activation pathway of complement. Journal of immunology (Baltimore, Md. : 1950) 26 10586086
2022 MASP-2 and MASP-3 inhibitors block complement activation, inflammation, and microvascular stasis in a murine model of vaso-occlusion in sickle cell disease. Translational research : the journal of laboratory and clinical medicine 25 35878790
2020 Association of Polymorphisms of MASP1/3, COLEC10, and COLEC11 Genes with 3MC Syndrome. International journal of molecular sciences 25 32751929
2014 Serum MASP-1 in complex with MBL activates endothelial cells. Molecular immunology 25 24472859
2011 Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) genotypes in colorectal cancer. Scandinavian journal of immunology 23 21198752
2006 Assembly of C1 and the MBL- and ficolin-MASP complexes: structural insights. Immunobiology 23 17544813
2005 Heterogeneity of MBL-MASP complexes. Molecular immunology 23 16102832
2017 Pentraxin 3, ficolin-2 and lectin pathway associated serine protease MASP-3 as early predictors of myocardial infarction - the HUNT2 study. Scientific reports 22 28216633
2019 Herpes simplex encephalitis in adult patients with MASP-2 deficiency. PLoS pathogens 21 31869396
2008 Purification, crystallization and preliminary X-ray analysis of human mannose-binding lectin-associated serine protease-1 (MASP-1) catalytic region. Acta crystallographica. Section F, Structural biology and crystallization communications 21 18765903
2019 Should MASP-2 Deficiency Be Considered a Primary Immunodeficiency? Relevance of the Lectin Pathway. Journal of clinical immunology 20 31828694
2018 Cutting Edge: A New Player in the Alternative Complement Pathway, MASP-1 Is Essential for LPS-Induced, but Not for Zymosan-Induced, Alternative Pathway Activation. Journal of immunology (Baltimore, Md. : 1950) 20 29475986
2013 The role of MASP-1/3 in complement activation. Advances in experimental medicine and biology 20 23402018
2013 Leprosy association with low MASP-2 levels generated by MASP2 haplotypes and polymorphisms flanking MAp19 exon 5. PloS one 20 23935922
1995 Localization of the genes for the 100-kDa complement-activating components of Ra-reactive factor (CRARF and Crarf) to human 3q27-q28 and mouse 16B2-B3. Genomics 20 7759119
2021 Targeting the Complement Serine Protease MASP-2 as a Therapeutic Strategy for Coronavirus Infections. Viruses 19 33671334
2011 Multiplex sequence-specific polymerase chain reaction reveals new MASP2 haplotypes associated with MASP-2 and MAp19 serum levels. Human immunology 19 21683108
2007 Genetic influences on mannan-binding lectin (MBL) and mannan-binding lectin associated serine protease-2 (MASP-2) activity. Genetic epidemiology 19 17096357
2000 A novel truncated isoform of the mannose-binding lectin-associated serine protease (MASP) from the common carp (Cyprinus carpio). Immunogenetics 19 10752628
2019 Expression and functional characterization of a mannose-binding lectin-associated serine protease-1 (MASP-1) from Nile tilapia (Oreochromis niloticus) in host defense against bacterial infection. Fish & shellfish immunology 18 31096060
2017 Mannan-binding lectin-associated serine protease-1 (MASP-1) mediates immune responses against Aeromonas hydrophila in vitro and in vivo in grass carp. Fish & shellfish immunology 18 28479400
2015 MASP-1 Induced Clotting--The First Model of Prothrombin Activation by MASP-1. PloS one 18 26645987
2014 Dissociation and re-association studies on the interaction domains of mannan-binding lectin (MBL)-associated serine proteases, MASP-1 and MASP-2, provide evidence for heterodimer formation. Molecular immunology 18 24424083
2020 C-reactive protein (CRP) recognizes uric acid crystals and recruits proteases C1 and MASP1. Scientific reports 17 32286427
2019 Reduced Mannose-Binding Lectin-Associated Serine Protease (MASP)-1 is Associated with Disturbed Coagulation in Septic Shock. Thrombosis and haemostasis 17 30986866
2017 Plasma levels of MASP-1, MASP-3 and MAp44 in patients with type 2 diabetes: influence of glycaemic control, body composition and polymorphisms in the MASP1 gene. Clinical and experimental immunology 17 28318015
2016 Experimentally-induced anti-myeloperoxidase vasculitis does not require properdin, MASP-2 or bone marrow-derived C5. The Journal of pathology 17 27235854
2005 Structure of model peptides based on Nephila clavipes dragline silk spidroin (MaSp1) studied by 13C cross polarization/magic angle spinning NMR. Biomacromolecules 17 16283749
2004 Phylogenetic placement of the spider genus Nephila (Araneae: Araneoidea) inferred from rRNA and MaSp1 gene sequences. Zoological science 17 15056930

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