Affinage

MASP2

Mannan-binding lectin serine protease 2 · UniProt O00187

Length
686 aa
Mass
75.7 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MASP-2 is the effector serine protease of the lectin pathway of complement, circulating in plasma complexed with the pattern-recognition molecules MBL and ficolins and cleaving complement components C4 and C2 to assemble the C3 convertase C4bC2a upon recognition of microbial surfaces (PMID:12396007, PMID:11426320, PMID:9777418, PMID:10586086, PMID:17204478). It is encoded by a single MASP2 gene on chromosome 1p36 that also produces the truncated, catalytically inactive splice product MAp19 through alternative splicing/polyadenylation, with both products synthesized predominantly in hepatocytes (PMID:11426320, PMID:10586086, PMID:21871896). MASP-2 cleaves C4 and C2 sequentially: C2 binds tightly only to nascent C4b rather than to native C4, and C4b remains transiently associated with MASP-2 after cleavage, a mechanism that localizes covalent C4b deposition near the activating MBL.MASP complex to favor convertase assembly (PMID:17204478). The high C4-cleavage efficiency that distinguishes MASP-2 from the homologous classical-pathway protease C1s is conferred by its CCP modules rather than its serine protease domain, whereas C2 cleavage efficiency is set by the SP domain (PMID:16227207, PMID:15364579). Although MASP-2 alone can cleave its substrates, efficient lectin-pathway activation requires MASP-1, which transactivates the MASP-2 zymogen; the two proteases are co-assembled within the same MBL or ficolin complex even though they do not form direct heterodimers (PMID:17182967, PMID:22511776, PMID:23785123). MASP-2 catalytic activity is controlled physiologically by C1-inhibitor, its major serpin, which inactivates MASP-2 far faster than it inactivates C1s (PMID:17709141, PMID:14725788). Loss-of-function MASP2 variants that abolish secretion or zymogen maturation cause MASP-2 deficiency associated with herpes simplex encephalitis, linking the lectin pathway to antiviral defense (PMID:31869396). Beyond its core complement role, MASP-2 has been established as a pathogenic mediator in post-ischemic brain injury, thrombotic microangiopathy, sickle cell vaso-occlusion, and coronavirus-associated injury, where antibody blockade is protective (PMID:27577570, PMID:33671334, PMID:35878790).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 High

    Established that MASP-2 and the truncated MAp19 derive from a single gene and that MASP-2 is the C4-cleaving protease within the MBL activation complex, synthesized in liver.

    Evidence Molecular cloning, Southern blot, tissue expression, and C4 cleavage assays in rat and mouse

    PMID:10586086

    Open questions at the time
    • Did not resolve the C2 cleavage step or convertase assembly
    • Hepatic restriction inferred from tissue expression, not lineage tracing
  2. 2000 High

    Defined the binding partitioning that gives the lectin pathway its specificity: MASP-2/MAp19 associate exclusively with MBL while C1r/C1s associate with C1q.

    Evidence Gel-permeation chromatography, C1r-deficient serum depletion, and complement activation assays

    PMID:10878362

    Open questions at the time
    • Most serum MASPs were not MBL-bound, leaving the function of free MASP pools unexplained
    • Ficolin partners not yet examined
  3. 2001 Medium

    Mapped MASP2 to chromosome 1p36 and established its evolutionary origin shared with C1s via exon shuffling, explaining the proteases' similar architecture and substrate specificity.

    Evidence Genomic sequencing and comparative gene structure analysis with C1s

    PMID:11426320

    Open questions at the time
    • Evolutionary inference, not functional
    • Did not address what distinguishes MASP-2 catalytic behavior from C1s
  4. 2004 High

    Provided the structural and enzymatic basis for MASP-2 catalysis, showing the CCP2 module stabilizes the SP domain, defining modular flexibility, and revealing that MASP-2 is best assayed on its natural substrate C4 because it barely cleaves small peptides.

    Evidence X-ray crystallography of the catalytic fragment, differential scanning calorimetry, and fluorescent substrate/inhibitor profiling

    PMID:14725788 PMID:15364579

    Open questions at the time
    • Full-length zymogen and complex architecture not resolved
    • Mechanism of substrate recognition by surface loops only partly defined
  5. 2004 High

    Solved the structure of the MAp19 splice product and mapped the CUB1 residues mediating Ca2+-dependent binding to MBL and L-ficolin, defining the shared docking site for pattern-recognition molecules.

    Evidence X-ray crystallography and SPR with point mutants

    PMID:15117939

    Open questions at the time
    • Binding site mapped on MAp19; full MASP-2/MBL complex geometry not determined
    • Physiological role of MAp19 binding left open
  6. 2005 High

    Dissected the structural determinants of MASP-2 substrate efficiency, attributing superior C4 cleavage to the CCP modules and C2 cleavage efficiency to the SP domain.

    Evidence C1s/MASP-2 chimera mutagenesis with quantitative kinetic characterization

    PMID:16227207

    Open questions at the time
    • Mechanism by which CCP modules enhance C4 docking not structurally visualized
  7. 2005 Medium

    Extended the partner repertoire by showing MASP-2 forms complement-active complexes with ficolin A, with sMAP/MAp19 acting as a competitive inhibitor.

    Evidence Recombinant reconstitution, co-immunoprecipitation, and complement activation assays in mouse

    PMID:16328467

    Open questions at the time
    • sMAP competition later contested under physiological conditions
    • Single lab, mouse system
  8. 2007 High

    Resolved the ordered convertase assembly mechanism: C2 binds nascent C4b rather than native C4, and C4b remains bound to MASP-2, localizing C4b deposition near the activating complex.

    Evidence SPR binding kinetics and enzymatic cleavage analysis of MASP-2, C4, C2 and fragments

    PMID:17204478

    Open questions at the time
    • Surface-bound convertase geometry on real pathogens not directly observed
  9. 2007 High

    Defined MASP-2 cleavage specificity by subsite, established it as up to 1000-fold more active than C1s on peptides, and identified C1-inhibitor as its principal physiological serpin.

    Evidence Phage display substrate library, peptide cleavage assays, and serpin inhibition kinetics

    PMID:17709141

    Open questions at the time
    • Specificity determined on peptides; relevance to additional natural substrates beyond C4/C2 not addressed
  10. 2012 High

    Established that both MASP-1 and MASP-2 are individually essential for lectin-pathway activation and that MASP-1 transactivates MASP-2 zymogen, with high-resolution Michaelis complexes revealing protease plasticity.

    Evidence Directed-evolution monospecific inhibitors, complement activation assays, and 1.28 A crystallography

    PMID:22511776

    Open questions at the time
    • Kinetics of transactivation in the assembled complex not fully quantified
  11. 2013 High

    Showed that MASP-1 and MASP-2 are co-assembled within a single MBL/ficolin complex (not direct heterodimers) to enable transactivation, and that MAp44 inhibits by disrupting these co-complexes.

    Evidence Co-immunoprecipitation, functional complement assays, and serum complex characterization

    PMID:23785123

    Open questions at the time
    • Stoichiometry and spatial arrangement within native complexes not structurally resolved
  12. 2011 Medium

    Quantified serum MAp19 and MASP-2 and overturned the model of MAp19 as a physiological competitive inhibitor of MASP-2, showing MAp19 does not displace MASP-2 from MBL under physiological conditions.

    Evidence Quantitative ELISA, serum fractionation, complement inhibition assays, and IHC/qRT-PCR

    PMID:21871896

    Open questions at the time
    • Physiological function of abundant free/urinary MAp19 remains unexplained
    • Conflicts with earlier mouse ficolin A data
  13. 2014 Medium

    Identified TFPI as a selective endogenous inhibitor of MASP-2 acting through its Kunitz-2 domain, expanding regulators beyond C1-inhibitor.

    Evidence Ex vivo C4 deposition and fluid-phase chromogenic assays with domain-specific blocking antibodies

    PMID:25359215

    Open questions at the time
    • Physiological significance of TFPI-mediated MASP-2 regulation in vivo not established
    • Single lab
  14. 2015 High

    Distinguished MASP function in factor D maturation, showing MASP-2 (and MASP-1) do not activate pro-factor D in plasma, isolating that role to MASP-3.

    Evidence Selective MASP inhibitors and recombinant MASP addition in plasma with kinetic pro-FD assays

    PMID:26673137

    Open questions at the time
    • Defines what MASP-2 does not do; no new MASP-2 substrate identified
  15. 2016 High

    Demonstrated a pathogenic role for MASP-2 in post-ischemic brain injury, with genetic and antibody-based loss of MASP-2 (but not MASP-1/3) conferring protection.

    Evidence MASP-2-/-, MASP-1/3-/-, fB-/- mice in MCAO models plus antibody blockade and IHC readouts

    PMID:27577570

    Open questions at the time
    • Lectin- versus alternative-pathway amplification contributions not fully separated
    • Human relevance inferred from mouse
  16. 2019 Medium

    Linked MASP2 loss-of-function variants to herpes simplex encephalitis, showing G634R abolishes secretion and zymogen maturation and implicating the MBL/MASP-2 pathway in antiviral defense.

    Evidence In vitro variant expression and autoactivation assays plus MBL-deficient murine HSE model

    PMID:31869396

    Open questions at the time
    • Causal chain from MASP-2 deficiency to human HSE not proven beyond association
    • Murine model used MBL deficiency as surrogate
  17. 2020 Medium

    Established MASP-2 as a direct mediator of endothelial injury in thrombotic microangiopathy, with anti-MASP2 antibody suppressing patient-plasma-induced endothelial caspase-8 activation.

    Evidence Patient-plasma MVEC caspase-8 activation assay +/- narsoplimab and plasma complement ELISA

    PMID:32681658

    Open questions at the time
    • In vitro endothelial readout; in vivo TMA causation not established
    • Single lab
  18. 2021 Low

    Proposed a direct MASP-2/coronavirus nucleocapsid interaction driving aberrant complement activation in viral lung injury.

    Evidence In silico screening with complement assays, citing prior antibody-blocking experiments

    PMID:33671334

    Open questions at the time
    • Primarily computational; mechanistic interaction rests on prior cited literature not new experiments
    • Direct binding not independently confirmed here
  19. 2022 Medium

    Extended MASP-2's pathogenic role to sickle cell disease, showing antibody inhibition reduces complement deposition, inflammation, and microvascular vaso-occlusion.

    Evidence Inhibitory anti-MASP-2 antibody in Townes SS mice with complement markers, IHC, and intravital microscopy

    PMID:35878790

    Open questions at the time
    • Single lab; relative contributions of lectin versus alternative pathway not fully dissected
    • Human therapeutic translation not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological function of the abundant free and urinary MAp19 pool and the in vivo relevance of non-canonical MASP-2 regulators (TFPI) and disease interactions remain unresolved.
  • No function assigned to non-MBL-bound MAp19
  • In vivo significance of TFPI-mediated MASP-2 inhibition unknown
  • Whether MASP-2 has substrates beyond C4/C2 not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016787 hydrolase activity 3
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 2
Partners
C2C4FCN1FCN2FCN3MASP1MBL2SERPING1
Complex memberships
MBL-MASP complexficolin-MASP complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 MASP-2 and MAp19 are alternative splice products of a single MASP2 gene; MASP-2 is the serine protease responsible for cleaving C4 and C2 to generate the C3 convertase C4bC2b in the lectin pathway, while MAp19 consists only of the first two domains of MASP-2 plus four additional residues and lacks a catalytic domain. Molecular cloning, gene structure analysis, and functional reconstitution assays Immunobiology High 10586086 11426320 12396007 9777418
2004 The crystal structure of the MASP-2 catalytic fragment (CCP2 + serine protease domain) was solved at 2.25 Å resolution. The CCP2 module stabilizes the SP domain structure. The asymmetric unit contains two molecules with different CCP-SP domain orientations, reflecting modular flexibility at the CCP2/SP joint. Despite nearly identical substrate specificities to C1s, MASP-2 achieves this through a different set of enzyme-substrate interactions, with surface loops (including S1 pocket loops) more similar to trypsin than C1s. X-ray crystallography at 2.25 Å resolution; differential scanning calorimetry Journal of molecular biology High 15364579
2004 MASP-1 cleaves fluorescent amide substrates (particularly Phe-Gly-Arg-AMC) rapidly, while recombinant MASP-2 barely cleaves any of 14 small fluorescent substrates tested. MASP-2 activity is best measured via cleavage of its natural protein substrate C4. C1-inhibitor inhibits both MASP-1 and MASP-2, but the protease-serpin complex is unusually unstable at alkaline pH. The thrombin inhibitor boroMpg inhibits MASP-1 but not MASP-2. Antithrombin III with heparin inhibits both MASPs. Fluorescent amide substrate cleavage assays with recombinant and serum-derived MASPs; inhibitor profiling Molecular immunology High 14725788
2004 The X-ray structure of MAp19 (the MASP2 alternative splice product) was solved at 2.5 Å. MAp19 forms a head-to-tail homodimer stabilized by Ca2+ ions at EGF modules. Point mutagenesis identified six residues (Tyr59, Asp60, Glu83, Asp105, Tyr106, Glu109) at the distal end of the CUB1 module that are critical for Ca2+-dependent interaction with MBL and L-ficolin, mapping a common binding site for these pattern recognition molecules. X-ray crystallography at 2.5 Å; surface plasmon resonance with point mutants The Journal of biological chemistry High 15117939
2000 In serum, MASP-1, MASP-2, and MAp19 associate exclusively with MBL (not C1q), while C1r and C1s associate exclusively with C1q. Full dissociation of MASPs/MAp19 from MBL requires both high salt and calcium chelation (EDTA). The bulk of MASP-1 and MAp19 in serum exist as large complexes with each other that are not bound to MBL or MASP-2, with over 95% of total MASPs and MAp19 not complexed with MBL. Gel-permeation chromatography; depletion experiments with C1r-deficient serum; complement activation assays on IgG- and mannan-coated microwells Journal of immunology High 10878362
2006 MASP-1 and MASP-2 cooperate to generate the C3 convertase through the MBL pathway. At high serum concentrations, MASP-2 alone is insufficient; MASP-1 must collaborate with MASP-2 for efficient C3b deposition on mannan-coated surfaces. MASP-3 inhibited this synergistic C3b deposition. C3b deposition required C4 and C2 (not factor B), confirming the lectin pathway mechanism. C3b deposition assay on mannan-coated surfaces using serum depleted of MASP-1, MASP-2, and MASP-3 with reconstitution experiments International immunology High 17182967
2007 MASP-2 cleaves C4 and C2 sequentially to form the C3 convertase. C2 does not bind to native C4 but binds tightly to C4b (generated after C4 cleavage), indicating C4 and C2 do not circulate as preformed complexes. C4b remains bound to MASP-2 after cleavage (KD ~0.6 µM, koff ~0.06 s-1), and this C4b.MASP-2 interaction is proposed to favor covalent attachment of C4b near the activating MBL.MASP complex on bacterial surfaces, thereby facilitating C3 convertase assembly. Surface plasmon resonance binding assays measuring interactions between MASP-2, C4, C2, and activation fragments; kinetic analysis of C4b2 and C2 cleavage The Journal of biological chemistry High 17204478
2007 Phage display substrate library screening revealed MASP-2 cleavage specificity: P1 position is critical, S2 and S3 subsites (preferring Gly at P2 and Leu/hydrophobic at P3) are the next most important determinants. MASP-2 is up to 1000-fold more catalytically active than C1s on peptide substrates. C1-inhibitor inhibits MASP-2 50-fold faster than it inhibits C1s, establishing MASP-2 as a major physiological target of C1-inhibitor. Randomised substrate phage display library; peptide substrate cleavage assays; serpin inhibition kinetics Molecular immunology High 17709141
2012 Both MASP-1 and MASP-2 are essential (not merely auxiliary) for lectin pathway activation. Monospecific evolved inhibitors selective for either MASP-1 or MASP-2 each completely block lectin pathway activation. MASP-1 transactivates MASP-2 zymogen. The first Michaelis-like complex structures of MASP-1 and MASP-2 with substrate-like inhibitors were solved, including a 1.28 Å MASP-2 structure revealing significant structural plasticity of the protease, suggesting induced fit or conformational selection contributes to its substrate specificity. Directed evolution of monospecific inhibitors; complement activation assays; X-ray crystallography at 1.28 Å (MASP-2 Michaelis complex) The Journal of biological chemistry High 22511776
2013 Although MASP-1 and MASP-2 do not directly form heterodimers, addition of MBL or ficolins (H-, L-, M-ficolin) enables formation of MASP-1–MASP-2 co-complexes within the same pattern recognition molecule complex. These co-complexes are functionally active in complement activation and are present in serum at varying levels that impact the degree of complement activation. MAp44 can inhibit complement not merely by displacing MASP-2 from MBL/ficolins, but by disrupting MASP-1–MASP-2 co-complexes and impairing transactivation. Co-immunoprecipitation; functional complement activation assays; serum complex characterization Journal of immunology High 23785123
2005 The higher C4 cleavage efficiency of MASP-2 compared to C1s arises from the complement control protein (CCP) modules of MASP-2, not from its serine protease domain. Chimeric molecules where MASP-2 CCP1/2 modules replaced those of C1s showed Km values in the nanomolar range for C4 (21–27-fold higher kcat/Km than C1s), while the SP domain swap did not confer this advantage. C2 cleavage efficiency was determined by the SP domain of each enzyme. Multisite-directed mutagenesis to generate C1s/MASP-2 chimeras; enzymatic characterization of C4 and C2 cleavage; esterolytic activity assays The Journal of biological chemistry High 16227207
2005 Mouse ficolin A and its splicing variant (but not ficolin B) form complexes with MASP-2 (and sMAP/MAp19), and these ficolin A/MASP-2 complexes show potent complement-activating capacity. sMAP competed with MASP-2 for binding to ficolin A and inhibited complement activation by the ficolin A/MASP-2 complex, establishing sMAP/MAp19 as a competitive inhibitor of MASP-2-mediated complement activation in this context. Recombinant protein production; co-immunoprecipitation; complement activation assays with purified components Immunogenetics Medium 16328467
1999 Rat and mouse MASP-2 and MAp19 are encoded by a single structural gene (as in humans), are components of the rat MBL pathway activation complex, and are synthesized exclusively in the liver. MASP-2 cleaves C4 within the MBL/MASP complex. Molecular cloning; Southern blot; PCR; hepatic biosynthesis demonstrated by tissue-specific expression analysis; functional C4 cleavage assay Journal of immunology High 10586086
2001 The human MASP2 gene is located on chromosome 1p36.23-31 and encodes both the 76 kDa MASP-2 serine protease and the 19 kDa MAp19 protein via alternative polyadenylation/splicing. Comparison with the C1s gene revealed identical positions of introns separating orthologous coding sequences, supporting the origin of MASP2 and C1s genes by exon shuffling from a common ancestral gene. Genomic sequencing; gene structure analysis; comparative genomics with C1s gene Genes and immunity Medium 11426320
2011 MAp19 serum concentration (~217 ng/ml, ~11 nM) is comparable to MASP-2 (~7 nM), but in serum all MASP-2 is associated with pattern recognition molecules (MBL, ficolins) while only a minor fraction of MAp19 is associated with them. Contrary to previous reports, MAp19 could NOT compete with MASP-2 for binding to MBL, nor inhibit MASP-2-mediated complement activation under physiological conditions. Both MAp19 and MASP-2 are expressed mainly in hepatocytes. High levels of MAp19 (but not MASP-2) are found in urine. Quantitative ELISA with monoclonal anti-MAp19 antibodies; serum fractionation; complement activation inhibition assays; immunohistochemistry combined with qRT-PCR Journal of immunological methods Medium 21871896
2016 MASP-2, but not MASP-1/3, critically mediates post-ischemic brain injury. MASP-2-deficient mice (MASP-2-/-) had significantly reduced neurological deficits, infarct volumes, C3 deposition, and pro-inflammatory microglia/macrophage activation after transient middle cerebral artery occlusion, while MASP-1/3-/- mice were not protected. Wild-type mice treated with a MASP-2-blocking antibody phenocopied MASP-2-/- mice. Factor B-deficient mice also showed protection, implicating both lectin and alternative pathway amplification. Genetic knockout mice (MASP-2-/-, MASP-1/3-/-, fB-/-); transient MCAO and 3-vessel occlusion models; antibody blockade; immunohistochemistry for C3 deposition and microglial morphology Journal of neuroinflammation High 27577570
2015 MASP-1 and MASP-2 (but not MASP-3) do not activate pro-factor D (pro-FD) in resting human blood at physiologically relevant concentrations, as established by selective MASP-1 and MASP-2 inhibitors failing to reduce pro-FD activation in plasma. Only MASP-3 added to plasma reduced the half-life of pro-FD, identifying MASP-3 as the likely physiological pro-FD activator. In purified systems, all three active MASPs and thrombin can cleave pro-FD, but MASP zymogens lack this activity. Fluorescently labeled pro-FD activation assay in serum/plasma; monospecific MASP-1 and MASP-2 inhibitors; recombinant MASP addition to plasma; kinetic analysis Journal of immunology High 26673137
2014 Tissue factor pathway inhibitor (TFPI) is a novel selective inhibitor of MASP-2 that does not affect MASP-1 or the classical pathway proteases C1s/C1r. The Kunitz-2 domain of TFPI is required for MASP-2 inhibition, as demonstrated by domain-specific monoclonal antibodies. TFPI inhibits MASP-2 activity both in a lectin pathway C4 deposition assay (ex vivo) and in a fluid-phase chromogenic MASP-2 activity assay. Ex vivo lectin pathway C4 deposition assay on mannan-coated plates; fluid-phase chromogenic MASP-2 activity assay; domain-specific monoclonal antibody blocking European journal of immunology Medium 25359215
2019 Two rare MASP2 variants (G634R and R203W) cause MASP-2 functional deficiency associated with herpes simplex encephalitis. The G634R variant abolished protein secretion and prevented cleavage of the MASP-2 precursor into its active form. The R203W variant reduced protein secretion. In a murine model, MBL-deficient mice had decreased survival and increased brain HSV-1 burden compared to wild-type mice, suggesting that the MBL/MASP-2 lectin pathway contributes to antiviral defense against HSV-1. In vitro expression of MASP2 variants; functional assays for secretion and autoactivation; murine HSE model with MBL-deficient mice PLoS pathogens Medium 31869396
2020 MASP-2 (the effector enzyme of the lectin pathway) mediates microvascular endothelial cell injury in thrombotic microangiopathies (TMAs). Plasmas from TMA patients induced MVEC caspase-8 activation in vitro, and this was suppressed by the anti-MASP2 monoclonal antibody narsoplimab (mean 65.7% inhibition), identifying MASP-2 as a direct mediator of complement-induced endothelial apoptosis/injury in TMA. ELISA for MASP-2 and sC5b-9 in patient plasmas; in vitro MVEC caspase-8 activation assay with patient plasmas ± narsoplimab Clinical and experimental immunology Medium 32681658
2021 MASP-2 contributes to aberrant complement activation triggered by coronavirus nucleocapsid (N) proteins through a direct, conserved interaction between MASP-2 and coronavirus N proteins (SARS-CoV, MERS-CoV, SARS-CoV-2). Blocking this MASP-2/N protein interaction with monoclonal antibodies or inhibiting MASP-2 catalytic activity alleviates coronavirus-induced lung injury in vitro and in vivo. In silico virtual screening; in vitro complement activation assays; reported prior experimental data (monoclonal antibody blocking of MASP-2/N-protein interaction with in vitro and in vivo lung injury endpoints) Viruses Low 33671334
2022 Inhibitory monoclonal antibodies against MASP-2 (lectin pathway) and MASP-3 (alternative pathway) each markedly reduced complement activation markers (Bb, C4d, C5a), complement deposition in liver/kidney/lung, NF-κB activation, adhesion molecule expression (VCAM-1, ICAM-1, E-selectin), and microvascular stasis (vaso-occlusion) in Townes sickle cell (SS) mice challenged with hypoxia-reoxygenation or hemoglobin, demonstrating that MASP-2 mediates lectin pathway-driven inflammation and vaso-occlusion in sickle cell disease. Inhibitory monoclonal antibodies against MASP-2 and MASP-3 in SS mice; hypoxia-reoxygenation and hemoglobin challenge; plasma complement markers by ELISA; immunohistochemistry for complement deposition; intravital microscopy for microvascular stasis Translational research Medium 35878790

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase II. Nature 1005 2842685
1992 The role of microtubule-associated protein 2 (MAP-2) in neuronal growth, plasticity, and degeneration. Journal of neuroscience research 313 1484385
1980 Structure and phosphorylation of microtubule-associated protein 2 (MAP 2). Proceedings of the National Academy of Sciences of the United States of America 257 6251448
1981 A protein kinase bound to the projection portion of MAP 2 (microtubule-associated protein 2). The Journal of cell biology 232 6270156
1983 Association of microtubule-associated protein 2 (MAP 2) with microtubules and intermediate filaments in cultured brain cells. The Journal of cell biology 188 6343400
1994 DLX-2, MASH-1, and MAP-2 expression and bromodeoxyuridine incorporation define molecularly distinct cell populations in the embryonic mouse forebrain. The Journal of neuroscience : the official journal of the Society for Neuroscience 185 7965042
1983 Microtubule assembly using the microtubule-associated protein MAP-2 prepared in defined states of phosphorylation with protein kinase and phosphatase. European journal of biochemistry 159 6140163
1991 ERKs, extracellular signal-regulated MAP-2 kinases. Current opinion in cell biology 142 1667578
2020 Safety, Tolerability and Efficacy of Narsoplimab, a Novel MASP-2 Inhibitor for the Treatment of IgA Nephropathy. Kidney international reports 130 33163724
1990 Stimulation of MAP-2 kinase activity in T lymphocytes by anti-CD3 or anti-Ti monoclonal antibody is partially dependent on protein kinase C. Journal of immunology (Baltimore, Md. : 1950) 130 2156931
2004 Differential substrate and inhibitor profiles for human MASP-1 and MASP-2. Molecular immunology 114 14725788
2005 Altered expression of MAP-2, GAP-43, and synaptophysin in the hippocampus of rats with chronic cerebral hypoperfusion correlates with cognitive impairment. Brain research. Molecular brain research 111 15964096
2021 hu.MAP 2.0: integration of over 15,000 proteomic experiments builds a global compendium of human multiprotein assemblies. Molecular systems biology 100 33973408
2002 The mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin pathway activation complex encoded by two genes. Immunobiology 96 12396007
1998 Disruption of MAP-2 immunostaining in rat hippocampus after traumatic brain injury. Journal of neurotrauma 91 9605349
2000 Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19. Journal of immunology (Baltimore, Md. : 1950) 89 10878362
1987 An immunocytochemical analysis of the ontogeny of the microtubule-associated proteins MAP-2 and Tau in the nervous system of the rat. Brain research 82 3113673
1990 CD-3-mediated activation of MAP-2 kinase can be modified by ligation of the CD4 receptor. Evidence for tyrosine phosphorylation during activation of this kinase. Journal of immunology (Baltimore, Md. : 1950) 80 2165097
1998 Making sense of the multiple MAP-2 transcripts and their role in the neuron. Molecular neurobiology 74 9588626
2006 Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway. International immunology 73 17182967
1995 Genomic structure of human microtubule-associated protein 2 (MAP-2) and characterization of additional MAP-2 isoforms. Proceedings of the National Academy of Sciences of the United States of America 70 7479905
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
1984 Widespread occurrence of polypeptides related to neurotubule-associated proteins (MAP-1 and MAP-2) in non-neuronal cells and tissues. The EMBO journal 68 6376120
1995 Abnormal expression of microtubule-associated protein 2 (MAP-2) in neocortex in Rett syndrome. Neuropediatrics 66 7566447
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
1993 Ammonium injection induces an N-methyl-D-aspartate receptor-mediated proteolysis of the microtubule-associated protein MAP-2. Journal of neurochemistry 65 8473887
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
1983 Differential distribution of microtubule-associated proteins MAP-1 and MAP-2 in neurons of rat brain and association of MAP-1 with microtubules of neuroblastoma cells (clone N2A). The EMBO journal 62 6641705
2011 MAp19, the alternative splice product of the MASP2 gene. Journal of immunological methods 59 21871896
1994 Antisense MAP-2 oligonucleotides induce changes in microtubule assembly and neuritic elongation in pre-existing neurites of rat cortical neurons. Cell motility and the cytoskeleton 57 8020109
1986 Identification of a MAP 2-like ATP-binding protein associated with axoplasmic vesicles that translocate on isolated microtubules. The Journal of cell biology 57 3091608
1994 Stimulation of tubulin polymerization by MAP-2. Control by protein kinase C-mediated phosphorylation at specific sites in the microtubule-binding region. The Journal of biological chemistry 56 7961787
1988 An immunocytochemical and biochemical study of the microtubule-associated protein MAP-2 during post-lesion dendritic remodeling in the central nervous system of adult rats. Brain research 56 3042088
1997 Calcium-stimulated phosphorylation of MAP-2 in pancreatic betaTC3-cells is mediated by Ca2+/calmodulin-dependent kinase II. The Journal of biological chemistry 55 9341200
1989 Cell cycle-dependent changes in the dynamics of MAP 2 and MAP 4 in cultured cells. The Journal of cell biology 51 2745548
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
2012 MBL2, MASP2, AMELX, and ENAM gene polymorphisms and dental caries in Polish children. Oral diseases 50 22221294
2020 MASP2 levels are elevated in thrombotic microangiopathies: association with microvascular endothelial cell injury and suppression by anti-MASP2 antibody narsoplimab. Clinical and experimental immunology 49 32681658
2004 The X-ray structure of human mannan-binding lectin-associated protein 19 (MAp19) and its interaction site with mannan-binding lectin and L-ficolin. The Journal of biological chemistry 49 15117939
1989 Multisite phosphorylation of microtubule-associated protein 2 (MAP-2) in rat brain: peptide mapping distinguishes between cyclic AMP-, calcium/calmodulin-, and calcium/phospholipid-regulated phosphorylation mechanisms. Journal of molecular neuroscience : MN 49 2561875
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
1997 Co-expression of MAP-2 and GFAP in cells developing from rat EGF responsive precursor cells. Brain research. Developmental brain research 48 9051273
1989 Complexing of the CD-3 subunit by a monoclonal antibody activates a microtubule-associated protein 2 (MAP-2) serine kinase in Jurkat cells. The Biochemical journal 48 2552997
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
2001 Abnormal patterns of microtubule-associated protein-2 (MAP-2) immunolabeling in neuronal nuclei and Lewy bodies in Parkinson's disease substantia nigra brain tissues. Neuroscience letters 46 11406314
1995 Degradation of fodrin and MAP 2 after neonatal cerebral hypoxic-ischemia. Brain research 46 7583214
1995 Microtubule-associated protein 2 (MAP-2): a sensitive marker of seizure-related brain damage. Journal of neuroscience methods 46 8618422
1985 Microheterogeneity of microtubule-associated proteins, MAP-1 and MAP-2, and differential phosphorylation of individual subcomponents. The Journal of biological chemistry 46 2985613
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
1993 Platelet-activating factor triggers the phosphorylation and activation of MAP-2 kinase and S6 peptide kinase activity in human B cell lines. Journal of immunology (Baltimore, Md. : 1950) 45 7688385
2010 Age-related decreases in SYN levels associated with increases in MAP-2, apoE, and GFAP levels in the rhesus macaque prefrontal cortex and hippocampus. Age (Dordrecht, Netherlands) 44 20640549
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
2022 Cardio-facio-cutaneous syndrome and gastrointestinal defects: report on a newborn with 19p13.3 deletion including the MAP 2 K2 gene. Italian journal of pediatrics 42 35509048
1985 Analysis of the microtubule-binding domain of MAP-2. The Journal of cell biology 42 4055896
1986 The binding of MAP-2 and tau on brain microtubules in vitro: implications for microtubule structure. Annals of the New York Academy of Sciences 40 3089106
2024 Diagnostic Performance of GFAP, UCH-L1, and MAP-2 Within 30 and 60 Minutes of Traumatic Brain Injury. JAMA network open 38 39230905
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
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
2002 MAP-2e, a novel MAP-2 isoform, is expressed in gliomas and delineates tumor architecture and patterns of infiltration. Journal of neuropathology and experimental neurology 34 12025943
1995 Non-cooperative binding of the MAP-2 microtubule-binding region to microtubules. The Journal of biological chemistry 34 7836356
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
1991 Activation of MAP-2 kinase activity by the CD2 receptor in Jurkat T cells can be reversed by CD45 phosphatase. Immunology 33 1676984
2015 Impact of MBL and MASP-2 gene polymorphism and its interaction on susceptibility to tuberculosis. BMC infectious diseases 31 25887173
2011 MASP2 gene polymorphism is associated with susceptibility to hepatitis C virus infection. Human immunology 31 21843573
1985 Expression of microtubule-associated proteins, MAP-1 and MAP-2, in human neuroblastomas and differential diagnosis of immature neuroblasts. Laboratory investigation; a journal of technical methods and pathology 31 3906271
1988 Microtubule-associated protein 2 (MAP 2) immunoreactivity in human fetal neocortex. Brain research 28 3293702
2009 Mannan-binding lectin-associated serine protease-2 (MASP-2) in a large cohort of neonates and its clinical associations. Molecular immunology 27 19307021
2004 The C. elegans methionine aminopeptidase 2 analog map-2 is required for germ cell proliferation. FEBS letters 27 15474045
1998 MASP-2, the C3 convertase generating protease of the MBLectin complement activating pathway. Immunobiology 27 9777418
2008 MBL2 and MASP2 gene polymorphisms in patients with hepatocellular carcinoma. Journal of viral hepatitis 26 18221301
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
2005 A study of a dendritic marker, microtubule-associated protein 2 (MAP-2), in rats neonatally treated neurosteroids, pregnenolone and dehydroepiandrosterone (DHEA). Neuroscience letters 25 16002213
2001 Molecular cloning of the complement (C1r/C1s/MASP2-like serine proteases from the common carp (Cyprinus carpio). Immunogenetics 25 11220628
1980 High molecular weight protein MAP 2 promoting microtubule assembly in vitro is associated with microtubules in cells. Cell biology international reports 25 7438221
2005 Novel MASP2 variants detected among North African and Sub-Saharan individuals. Tissue antigens 24 16029433
2011 Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) genotypes in colorectal cancer. Scandinavian journal of immunology 23 21198752
2003 Diagnostic value of microtubule-associated protein-2 (MAP-2) for neuroendocrine neoplasms. Advances in anatomic pathology 23 12605092
2001 NMDA-induced phosphorylation of the microtubule-associated protein MAP-2 is mediated by activation of nitric oxide synthase and MAP kinase. The European journal of neuroscience 22 11298788
2019 Herpes simplex encephalitis in adult patients with MASP-2 deficiency. PLoS pathogens 21 31869396
1992 Dietary aluminum selectively decreases MAP-2 in brains of developing and adult rats. Neurotoxicology 21 1331920
1986 Molecular aspects of MAP-1 and MAP-2: microheterogeneity, in vitro localization and distribution in neuronal and nonneuronal cells. Annals of the New York Academy of Sciences 21 3460414
2019 Should MASP-2 Deficiency Be Considered a Primary Immunodeficiency? Relevance of the Lectin Pathway. Journal of clinical immunology 20 31828694
2018 Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice. International journal of molecular sciences 20 29677125
2013 Leprosy association with low MASP-2 levels generated by MASP2 haplotypes and polymorphisms flanking MAp19 exon 5. PloS one 20 23935922
2008 Association of Gap-43 (neuromodulin) with microtubule-associated protein MAP-2 in neuronal cells. Biochemical and biophysical research communications 20 18455509
2002 Microtubule-associated protein 2 (MAP-2) is expressed in low and high grade diffuse astrocytomas. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 20 11922706
1995 Diminished expression of microtubule-associated protein (MAP-2) and beta-tubulin as a putative marker for ischemic injury in neocortical transplants. Cell transplantation 20 7728337
1989 Association of acetylated microtubules, vimentin intermediate filaments, and MAP 2 during early neural differentiation in EC cell culture. Biochemistry and cell biology = Biochimie et biologie cellulaire 20 2679799
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
1994 Exploring the microtubule-binding region of bovine microtubule-associated protein-2 (MAP-2): cDNA sequencing, bacterial expression, and site-directed mutagenesis. Biochemistry 19 7947727
2013 Calretinin and microtubule-associated protein-2 (MAP-2) immunohistochemistry in the diagnosis of Hirschsprung's disease. Journal of pediatric surgery 18 24094966
2012 Mutations of complement lectin pathway genes MBL2 and MASP2 associated with placental malaria. Malaria journal 18 22380611
2009 Utility of microtubule associated protein-2 (MAP-2) immunohistochemistry for identification of ganglion cells in paraffin-embedded rectal suction biopsies. The American journal of surgical pathology 18 19363440
2009 Lack of association between polymorphisms of MASP2 and susceptibility to SARS coronavirus infection. BMC infectious diseases 18 19405982

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