Affinage

MBL2

Mannose-binding protein C · UniProt P11226

Round 2 corrected
Length
248 aa
Mass
26.1 kDa
Annotated
2026-04-28
130 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MBL2 encodes mannose-binding lectin (MBL), a liver-secreted, calcium-dependent C-type lectin that functions as a central pattern-recognition molecule of innate immunity and the initiating component of the lectin complement pathway. The mature protein assembles from ~31 kDa subunits into trimers stabilized by a collagen-like domain and a coiled-coil neck region, which further oligomerize via N-terminal disulfide bonds into ~600 kDa higher-order structures that bind mannosylated glycans on bacteria, fungi, and enveloped viruses (including influenza, HIV-1, and SARS-CoV), triggering complement activation through associated serine proteases MASP-1 and MASP-2 that cleave C4, C2, and downstream components (PMID:6643429, PMID:9087411, PMID:15838797, PMID:10639434). MBL also promotes phagocytic clearance of apoptotic cells by engaging calreticulin/CD91 on macrophages (PMID:11560994), and MBL-dependent complement activation by tumor-associated fungi drives pancreatic ductal adenocarcinoma progression via C3a/C3aR signaling (PMID:31578522). Common point mutations at codons 52, 54, and 57 of exon 1 disrupt collagen-like triple-helix formation, reduce serum MBL and complement-activating capacity, and cause an opsonic defect associated with susceptibility to recurrent infections (PMID:1675710, PMID:1304173, PMID:8206524).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1983 High

    Identification of MBL as a discrete serum lectin resolved the molecular identity of the mannan-binding opsonic activity in human plasma, establishing its calcium-dependent carbohydrate-binding specificity and oligomeric architecture.

    Evidence Affinity chromatography on mannan-Sepharose with Scatchard binding analysis of human serum

    PMID:6643429

    Open questions at the time
    • Subunit stoichiometry and quaternary structure not determined
    • Gene encoding the protein not yet cloned
  2. 1988 High

    cDNA cloning revealed that MBL2 encodes a three-domain protein (N-terminal cysteine-rich, collagen-like, C-terminal CRD) homologous to C-type lectins and expressed as a liver acute-phase reactant, providing the structural framework for understanding oligomer assembly and ligand recognition.

    Evidence cDNA cloning from human liver library with full sequence analysis

    PMID:2450948

    Open questions at the time
    • Genomic structure and chromosomal location unknown
    • Mechanism of complement activation not yet linked to MBL
  3. 1989 High

    Two advances established MBL as a functional opsonin and mapped the gene: the MBL2 locus was placed at 10q11.2-q21 with a four-exon structure, and purified MBL was shown to correct a common opsonic defect by promoting C3b deposition in a dose-dependent manner.

    Evidence Genomic cloning with in situ hybridization; in vitro opsonization and C3b deposition reconstitution assay

    PMID:2477486 PMID:2573758

    Open questions at the time
    • Genetic basis of the opsonic defect not yet identified
    • Mechanism linking MBL to complement activation (serine protease partners) unknown
  4. 1992 High

    Discovery of exon 1 point mutations at codons 54 and 57 (and subsequently codon 52 in 1994) explained MBL deficiency: each substitutes a carboxylic acid for an axial glycine in the collagen-like domain, disrupting triple-helix assembly and lowering serum MBL, with distinct mutations predominating in different ethnic groups.

    Evidence DNA sequencing, family segregation, restriction analysis across Eskimo/Caucasian/African populations, complement activation assays

    PMID:1304173 PMID:1675710 PMID:8206524

    Open questions at the time
    • Precise structural consequence of each mutation on oligomer assembly not visualized
    • Promoter contributions to MBL levels only partially characterized
  5. 1994 High

    Crystal structure of the CRD-neck trimer revealed the coiled-coil neck organizing three CRDs into a fixed spatial array, explaining how MBL achieves avidity for clustered carbohydrate epitopes on microbial surfaces.

    Evidence X-ray crystallography of recombinant neck+CRD fragment in two crystal forms

    PMID:7634089

    Open questions at the time
    • Full-length oligomer structure not determined
    • Atomic details of carbohydrate-bound CRD not resolved in this study
  6. 1997 High

    Discovery of MASP-2 as the second MBL-associated serine protease, capable of cleaving C4 and C2, established that the lectin pathway parallels the classical pathway architecture with two distinct proteases, and defined the enzymatic mechanism by which MBL triggers complement.

    Evidence Protein purification and cDNA cloning of MASP-2 with C4/C2 cleavage assays

    PMID:9087411

    Open questions at the time
    • Relative contributions of MASP-1 vs MASP-2 to complement activation in vivo unclear
    • Stoichiometry and heterogeneity of MBL-MASP complexes not resolved
  7. 2001 High

    Two findings expanded MBL function beyond complement: MBL was shown to promote macropinocytic engulfment of apoptotic cells via calreticulin/CD91 on phagocytes, and MASP-3 was identified as a preferential partner of larger MBL oligomers that downregulates MASP-2-mediated complement activation, revealing oligomer-specific complex heterogeneity.

    Evidence Co-IP and blocking antibody experiments for calreticulin/CD91 with phagocytosis assays; MASP-3 cloning with oligomer fractionation and C4/C2/C3 cleavage assays

    PMID:11485744 PMID:11560994

    Open questions at the time
    • In vivo contribution of calreticulin/CD91 pathway to apoptotic clearance not tested
    • Regulatory interplay among MASP-1, MASP-2, and MASP-3 in vivo not quantified
  8. 2005 High

    Demonstration that MBL binds enveloped viruses—HIV-1 gp120 and SARS-CoV—through high-mannose glycans, directly neutralizing infectivity and activating complement, broadened MBL's recognized pathogen spectrum to include viruses and linked MBL2 genotype to susceptibility to emerging infections.

    Evidence Calcium-dependent binding assays, mannan competition, C4 deposition on virions, neutralization assays, DC-SIGN blocking, and case-control genotyping

    PMID:15488604 PMID:15838797

    Open questions at the time
    • Whether MBL-mediated viral neutralization is significant in vivo at physiological MBL concentrations remains untested in animal models
    • Relative contribution of direct neutralization versus complement opsonization not dissected
  9. 2004 High

    MBL double-knockout mice demonstrated that MBL is essential for in vivo defense against S. aureus (100% lethality in KO vs 45% in WT), directly proving the non-redundant protective role inferred from human deficiency studies.

    Evidence MBL-A/MBL-C double-KO mice with IV and IP S. aureus infection, survival analysis, neutrophil depletion

    PMID:15148336

    Open questions at the time
    • Murine system has two MBL genes; direct extrapolation to single-gene human MBL2 deficiency requires caution
    • Whether the lethal phenotype reflects complement activation, opsonophagocytosis, or both not fully resolved
  10. 2014 High

    Identification of MASP-1 as the MBL-MASP complex component that activates endothelial cells via PAR-4 cleavage, combined with its fibrinogen/Factor XIII substrates, established that the MBL pathway intersects coagulation and vascular inflammation beyond canonical complement.

    Evidence Ca²⁺ signaling in HUVECs with recombinant MASP catalytic fragments and stable zymogen mutant; prior enzymatic assays showing fibrinogen and Factor XIII cleavage by MASP-1

    PMID:12396008 PMID:24472859

    Open questions at the time
    • In vivo significance of MASP-1-PAR-4 endothelial activation not demonstrated
    • Whether MBL oligomer composition determines MASP-1 vs MASP-2 signaling outputs in vascular contexts is unknown
  11. 2019 High

    A non-canonical role for MBL2 in cancer was established: tumor-infiltrating fungi activate MBL, which triggers complement (C3/C3aR) to promote pancreatic ductal adenocarcinoma growth; Mbl2 deletion blocks this tumor-promoting pathway, demonstrating that MBL-mediated complement can be co-opted for oncogenesis.

    Evidence MBL2-KO and C3-KO mice, C3aR knockdown in tumor cells, mycobiome manipulation in slow-progressive and invasive PDA models

    PMID:31578522

    Open questions at the time
    • Whether this mechanism extends to other fungal-colonized tumors is untested
    • The specific fungal glycan(s) recognized by MBL in the tumor microenvironment are not characterized
    • Therapeutic targeting of MBL in PDA not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the full-length oligomeric structure of MBL-MASP complexes at atomic resolution, the in vivo balance between protective antimicrobial and deleterious inflammatory/pro-tumorigenic roles of MBL-mediated complement activation, and whether therapeutic MBL replacement can safely correct immunodeficiency without exacerbating complement-driven pathology.
  • No full-length MBL oligomer atomic structure available
  • No clinical trial data on recombinant MBL replacement in the timeline
  • Context-dependent switching between protective and pathological MBL functions is mechanistically undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0048018 receptor ligand activity 3
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-168256 Immune System 6 R-HSA-109582 Hemostasis 2 R-HSA-1643685 Disease 1
Partners
CALRLRP1MASP1MASP2SERPING1
Complex memberships
MBL-MASP-1 complexMBL-MASP-2 complexMBL-MASP-3 complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1983 MBL2 protein (mannan-binding protein) was isolated from human serum as a glycine-rich lectin of ~600 kDa composed of ~31 kDa subunits, with calcium-dependent, saturable, and reversible binding to mannan distinct from CRP and SAP. Affinity chromatography on Sepharose-mannan, Scatchard plot binding analysis, immunoassay Journal of biochemistry High 6643429
1988 MBL2 encodes a human serum lectin with three structural domains: an N-terminal cysteine-rich region (interchain disulfide bonds), a collagen-like region (19 Gly-X-Y repeats), and a C-terminal carbohydrate recognition domain; the protein is an acute-phase reactant secreted by the liver and homologous to C-type lectins. cDNA cloning from human liver library, sequence analysis, comparison with rat MBP and other lectins The Journal of experimental medicine High 2450948
1989 The MBL2 gene is located on chromosome 10q11.2-q21, comprises four exons each encoding a distinct protein domain, and evolved by recombination of an ancestral non-fibrillar collagen gene with a carbohydrate-recognition gene, similar to surfactant SP-A. Genomic cloning, exon structure analysis, chromosomal localization by in situ hybridization The Journal of experimental medicine High 2477486
1989 Low serum MBL levels are directly linked to a common opsonic defect; purified MBL corrects the defect in a dose-dependent manner by promoting C3b deposition on mannan-coated surfaces, establishing MBL as a functional opsonin. In vitro opsonization assay measuring complement C3b deposition on mannan-coated surfaces, immunoassay of serum MBL levels Lancet High 2573758
1991 A point mutation at codon 54 of MBL2 exon 1 (GGC→GAC, Gly→Asp) disrupts the fifth Gly-X-Y repeat of the collagen-like domain, prevents normal triple helix formation, and causes low serum MBL with autosomal dominant co-inheritance of the opsonic defect. DNA sequencing of MBL2 exon 1, family segregation analysis, serum MBL immunoassay Lancet High 1675710
1992 Two independent point mutations in MBL2 exon 1 — codon 54 (GGC→GAC) prevalent in non-Africans and codon 57 (GGA→GAA) prevalent in West Africans — each substitute carboxylic acids for axial glycines, disrupting the collagen-like triple helix and profoundly reducing serum MBL and complement activation capacity. PCR, sequence analysis, restriction analysis of population samples, complement activation assay Human molecular genetics High 1304173
1994 A third MBL2 exon 1 point mutation at codon 52 was identified, completing the structural polymorphism; together codons 52, 54, and 57 account for all cases of MBL deficiency across ethnic groups in Hardy-Weinberg equilibrium. PCR-based genotyping, population genetic analysis (Hardy-Weinberg testing) across Eskimo, Caucasian, and African populations Immunogenetics High 8206524
1994 The carbohydrate recognition domain (CRD) and 'neck' region of MBL2 form a trimeric structure in solution and crystals; the neck region forms a triple α-helical coiled-coil, and each α-helix contacts a neighboring CRD, defining the spatial arrangement of CRDs for branched oligosaccharide recognition on microorganisms. X-ray crystallography of recombinant neck+CRD peptide in two crystal forms Nature structural biology High 7634089
1994 MBL2 binds to influenza virus through its lectin domain in a calcium-dependent, saturable, concentration-dependent manner; ligand blot analysis identified the 68 kDa viral neuraminidase as the specific MBL-binding species, and bound MBL inhibits hemagglutinating activity. Saturable binding assay, ligand blot, purification of the 68 kDa MBL-binding viral protein and identification as neuraminidase, hemagglutination inhibition assay The Biochemical journal High 7998980
1997 A second MBL-associated serine protease, MASP-2, was identified; MASP-2 associates with MBL oligomers and activates complement via C4 and C2 cleavage, demonstrating that the MBL pathway, like the classical pathway, involves two serine proteases (MASP-1 and MASP-2). Protein purification, cDNA cloning, sequence homology analysis, complement C4 and C2 cleavage assays Nature High 9087411
1998 Low MBL serum concentrations in African and South American populations are caused by distinct molecular mechanisms: high frequency of the codon 57 (C) variant in Africans versus extremely high frequency of the codon 54 (B) variant in South American natives, with promoter haplotypes further modulating levels. MBL2 genotyping, serum MBL concentration measurement, population allele frequency analysis Journal of immunology High 9743385
1998 Chicken MBL is a single-form serum collectin with structural homology to mammalian MBL; phylogenetic analysis indicates that the gene duplication producing two MBL forms in mammals (MBL1 and MBL2) occurred after the bird-reptile split, supporting the evolutionary origin of the MBL2 locus. RT-PCR, cDNA library screening, sequencing, phylogenetic analysis of deduced amino acid sequences Immunology Medium 9640255
2000 MBL binds to a broad range of clinically relevant pathogens (Candida spp., Aspergillus fumigatus, S. aureus, beta-hemolytic group A streptococci) and bound MBL promotes C4 deposition in a concentration-dependent manner, directly linking pathogen surface recognition to complement activation. Flow cytometry binding assay with purified MBL on pathogen isolates, C4 deposition assay Infection and immunity High 10639434
2000 MBL-MASP complex activity is controlled by C1 inhibitor (which inhibits both classical and MBL pathways) but not by α2-macroglobulin; C1 inhibitor and α2-macroglobulin both associate with the MBL complex, and MASP-1, MASP-2, and MAp19 dissociate from MBL at 37°C in physiological buffer but not at high ionic strength (1M NaCl), indicating the MBL-MASP interaction is distinct from the C1 complex. Complement activation assay specific for MBL pathway, co-purification/association analysis, inhibitor profiling Molecular immunology High 11257302
2001 MBL2 binds to apoptotic cells and, via ligation of calreticulin (cC1qR) on phagocytes which in turn binds CD91 (α2-macroglobulin receptor), stimulates macropinocytic engulfment of apoptotic cells, identifying a novel receptor-ligand mechanism for MBL-mediated apoptotic cell clearance. Co-IP, calreticulin/CD91 blocking antibodies, macropinocytosis assay, apoptotic cell uptake quantification The Journal of experimental medicine High 11560994
2001 MASP-3, generated by alternative splicing of the MASP-1/3 gene, associates preferentially with larger MBL oligomers together with MASP-2, and downregulates the C4 and C2 cleaving activity of MASP-2; smaller MBL oligomers preferentially associate with MASP-1, MAp19, and direct C3-cleaving activity, demonstrating that distinct MBL oligomers form functionally different complexes. Protein purification, cDNA cloning, alternative splicing analysis, functional C4/C2/C3 cleavage assays, oligomer fractionation Immunity High 11485744
2002 MASP-1, despite initial suggestions, does not efficiently cleave C3 directly at biologically relevant rates; instead, MASP-1 cleaves fibrinogen (releasing fibrinopeptide B) and activates plasma transglutaminase (Factor XIII), indicating MASPs have biologically significant substrates beyond complement components. In vitro cleavage assays with recombinant and purified native MASP-1, fibrinogen cleavage, Factor XIII activation assay Immunobiology High 12396008
2002 MBL2 genotypes (promoter and structural SNPs at codons 52, 54, 57 and promoter positions -550, -221) show significant correlation with plasma MBL antigen levels and functional MBL activity as measured by both mannan-binding and C4-deposition assays, validating comprehensive genotype-phenotype relationships. PCR-SSP genotyping, double-antibody ELISA for MBL antigen, mannan-binding assay, C4-deposition assay in 236 blood donors Scandinavian journal of immunology High 12472676
2003 Recombinant MBL produced in a transfected human cell line shows identical biological activity and MS profile to plasma-derived MBL, demonstrating that the oligomeric structure and function can be reconstituted recombinantly, enabling therapeutic application. Recombinant protein production in human cell line, mass spectrometry, functional activity comparison with plasma-derived MBL Biochemical Society transactions Medium 12887299
2004 MBL-null mice (lacking both MBL-A and MBL-C) show 100% mortality within 48h of intravenous S. aureus infection compared to 45% mortality in wild-type mice, directly demonstrating that MBL is essential for in vivo host defense against S. aureus; neutrophils and MBL cooperate to limit intraperitoneal infection. MBL-A and MBL-C double gene knockout mice, intravenous and intraperitoneal S. aureus infection models, survival analysis, neutrophil depletion experiments The Journal of experimental medicine High 15148336
2005 MBL binds to HIV-1 gp120 through high-mannose glycans on the envelope protein in a calcium-dependent, strain-independent manner; MBL can directly neutralize HIV produced in T-cell lines, activate complement on gp120, opsonize HIV, and block HIV interaction with DC-SIGN. Binding assays (ELISA, flow cytometry), neutralization assays, complement C4 deposition on gp120, DC-SIGN blocking assay Molecular immunology High 15488604
2005 MBL serum levels vary widely due to MBL2 polymorphisms, and genetically determined differences in complement activation via MBL may play a role in diabetic micro- and macrovascular complications, with complement activation following ischemia-reperfusion as a proposed mechanism. Review of functional MBL complement activation data and clinical association studies Hormone and metabolic research Low 15918118
2005 MBL binds to SARS-CoV in a dose-dependent, calcium-dependent, and mannan-inhibitable manner (confirming binding through the CRDs), enhances complement C4 deposition on SARS-CoV, and inhibits viral infectivity in FRhK-4 cells; lower MBL levels/haplotypes associated with SARS acquisition. In vitro binding assay, mannan competition, C4 deposition on SARS-CoV, infectivity inhibition assay in cell culture, case-control genotyping The Journal of infectious diseases High 15838797
2006 C1r/C1s and MASP-1/MASP-2 associate through a common mechanism involving their N-terminal CUB1-EGF region, but the C1s-C1r-C1r-C1s tetramer and (MASP)₂ dimers have evolved distinct strategies to associate with their recognition proteins (C1q vs. MBL/ficolins), establishing the structural basis for MBL-MASP complex assembly. Structural analysis (crystallography), functional domain mapping, comparison of C1 and MBL-MASP complexes Immunobiology Medium 17544813
2009 MASP-2 polymorphisms D120G and CHNHdup abolish binding to MBL (preventing complement C4 cleavage), while R439H binds MBL normally but cannot autoactivate or cleave C4, identifying distinct molecular defects in MASP-2 function; the R439H variant is common in Sub-Saharan Africans (10% gene frequency). Recombinant MASP-2 production for each naturally occurring variant, MBL-binding assay, C4 cleavage assay, autoactivation assay Journal of immunology High 19234189
2010 In MBL-KO mice, MBL deficiency is protective (not detrimental) in experimental systemic aspergillosis: KO mice were less susceptible to lethal infection than wild-type at certain inocula, suggesting MBL plays a deleterious role in systemic aspergillosis, possibly through excessive complement-mediated inflammation. MBL-A and MBL-C double gene knockout mice, intravenous Aspergillus fumigatus infection model, dose-response survival analysis Immunology letters Medium 20064561
2014 Among MBL-MASP complexes, only MASP-1 (not MASP-2, MASP-3, or non-enzymatic MASP domains) activates endothelial cells (Ca²⁺ signaling in HUVECs) when present in the serum MBL-MASP complex; this activation requires MASP-1's proteolytic activity (zymogen mutant is inactive) and occurs via cleavage of protease-activated receptor 4 (PAR-4). Ca²⁺ signaling assay in HUVECs, recombinant MASP catalytic fragments, stable zymogen MASP-1 mutant, serum-derived MBL-MASP complexes Molecular immunology High 24472859
2015 MBL-MASP complexes are heterogeneous in serum; MASP-1 activity per unit MBL is inversely correlated with MASP-2 activity per unit MBL across individuals, consistent with separate populations of MBL-MASP-1 and MBL-MASP-2 complexes rather than fixed stoichiometric MBL-(MASP-1)-(MASP-2) trimolecular complexes. Mannan-plate capture of MBL from 152 individual sera, ELISA for MBL, amidolytic assay for MASP-1, C4-fixation assay for MASP-2; correlation analysis Molecular immunology Medium 16102832
2015 Fasciola hepatica newly excysted juveniles (NEJ) resist MBL-mediated complement killing by two mechanisms: (1) MBL does not bind to the NEJ surface despite mannosylated surface proteins, and (2) secreted NEJ serpins (rFhSrp1, rFhSrp2) directly inhibit MASP-1 and MASP-2, preventing C3b and C4b deposition. In vitro MBL binding assay on live NEJ, recombinant serpin production, MASP-1 and MASP-2 inhibition assays, immunofluorescence for MBL/C3b/C4b/MAC deposition on NEJ in human serum PLoS pathogens High 35007288
2019 Fungi (especially Malassezia spp.) that migrate into pancreatic ductal adenocarcinoma (PDA) tumors activate MBL2 through binding to fungal wall glycans, triggering complement cascade activation (C3); deletion of MBL2 or C3, or knockdown of C3aR in tumor cells, protects against tumor growth, and reprogramming the mycobiome does not alter PDA progression in Mbl2-deficient mice, establishing MBL2-mediated complement as required for fungus-driven oncogenesis. MBL2 and C3 knockout mice, C3aR knockdown in tumor cells, mycobiome ablation/repopulation experiments, tumor growth assays in slow-progressive and invasive PDA mouse models Nature High 31578522

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2012 Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nature genetics 958 22504420
2001 C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. The Journal of experimental medicine 902 11560994
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2019 The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature 672 31578522
1997 A second serine protease associated with mannan-binding lectin that activates complement. Nature 667 9087411
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1991 Molecular basis of opsonic defect in immunodeficient children. Lancet (London, England) 492 1675710
1989 Association of low levels of mannan-binding protein with a common defect of opsonisation. Lancet (London, England) 458 2573758
1994 A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding protein. Immunogenetics 443 8206524
2000 Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infection and immunity 442 10639434
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2001 Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood. JAMA 350 11255386
1993 A role for the transcription factors Mbp1 and Swi4 in progression from G1 to S phase. Science (New York, N.Y.) 339 8372350
2016 A journey through the lectin pathway of complement-MBL and beyond. Immunological reviews 324 27782323
1998 Different molecular events result in low protein levels of mannan-binding lectin in populations from southeast Africa and South America. Journal of immunology (Baltimore, Md. : 1950) 315 9743385
1992 High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene. Human molecular genetics 302 1304173
1995 Mannose binding protein gene mutations associated with unusual and severe infections in adults. Lancet (London, England) 297 7707811
1989 Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages. The Journal of experimental medicine 295 2477488
2001 MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 278 11485744
2002 The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20. Molecular cell 268 11804586
1988 A human mannose-binding protein is an acute-phase reactant that shares sequence homology with other vertebrate lectins. The Journal of experimental medicine 258 2450948
1989 The human mannose-binding protein gene. Exon structure reveals its evolutionary relationship to a human pulmonary surfactant gene and localization to chromosome 10. The Journal of experimental medicine 242 2477486
1983 Isolation and characterization of a mannan-binding protein from human serum. Journal of biochemistry 241 6643429
2002 MBL genotype and risk of invasive pneumococcal disease: a case-control study. Lancet (London, England) 237 12047967
2001 The mannan-binding lectin pathway of complement activation: biology and disease association. Molecular immunology 230 11532276
2007 Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. The Journal of infectious diseases 223 17703412
2005 Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection. The Journal of infectious diseases 221 15838797
2004 Mannose-binding lectin-deficient mice are susceptible to infection with Staphylococcus aureus. The Journal of experimental medicine 220 15148336
2009 Genetic modifiers of liver disease in cystic fibrosis. JAMA 213 19738092
1994 Human mannose-binding protein carbohydrate recognition domain trimerizes through a triple alpha-helical coiled-coil. Nature structural biology 203 7634089
2010 Monoclonal B-cell lymphocytosis (MBL): biology, natural history and clinical management. Leukemia 171 20090778
2002 Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an Australian blood donor population. Scandinavian journal of immunology 161 12472676
2017 Antagonistic Functions of MBP and CNP Establish Cytosolic Channels in CNS Myelin. Cell reports 151 28076777
2002 Nuclear retention of MBP mRNAs in the quaking viable mice. Neuron 148 12467586
1998 Mannose-binding lectin (MBL) in health and disease. Immunobiology 140 9777416
1996 Arabidopsis MBP1 gene encodes a conserved ubiquitin recognition component of the 26S proteasome. Proceedings of the National Academy of Sciences of the United States of America 124 8570648
2009 MBL2, FCN1, FCN2 and FCN3-The genes behind the initiation of the lectin pathway of complement. Molecular immunology 121 19501910
2002 The biological functions of MBL-associated serine proteases (MASPs). Immunobiology 118 12396008
2000 Control of the classical and the MBL pathway of complement activation. Molecular immunology 109 11257302
2010 MBP-1 upregulates miR-29b that represses Mcl-1, collagens, and matrix-metalloproteinase-2 in prostate cancer cells. Genes & cancer 105 20657750
2005 Mannose binding lectin (MBL) and HIV. Molecular immunology 105 15488604
2015 Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation. Molecular cell 94 25728769
1997 Xbp1, a stress-induced transcriptional repressor of the Saccharomyces cerevisiae Swi4/Mbp1 family. Molecular and cellular biology 92 9343412
2010 Different biology and clinical outcome according to the absolute numbers of clonal B-cells in monoclonal B-cell lymphocytosis (MBL). Cytometry. Part B, Clinical cytometry 83 20839333
2010 Hypoxia induces differential translation of enolase/MBP-1. BMC cancer 72 20412594
1994 Binding of human collectins (SP-A and MBP) to influenza virus. The Biochemical journal 72 7998980
2013 Immunogenetics shows that not all MBL are equal: the larger the clone, the more similar to CLL. Blood 68 23596047
2003 Recombinant mannan-binding lectin (MBL) for therapy. Biochemical Society transactions 62 12887299
2019 Monobutyl phthalate (MBP) can dysregulate the antioxidant system and induce apoptosis of zebrafish liver. Environmental pollution (Barking, Essex : 1987) 61 31761585
2009 Polymorphisms in mannan-binding lectin (MBL)-associated serine protease 2 affect stability, binding to MBL, and enzymatic activity. Journal of immunology (Baltimore, Md. : 1950) 55 19234189
1989 Morphological distribution of MBP-like immunoreactivity in the brain during development. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 54 2469297
2015 MBL-associated serine proteases (MASPs) and infectious diseases. Molecular immunology 51 25862418
2005 Expression of MBP, PLP, MAG, CNP, and GFAP in the Human Alcoholic Brain. Alcoholism, clinical and experimental research 50 16205370
1999 Association of the cell cycle transcription factor Mbp1 with the Skn7 response regulator in budding yeast. Molecular biology of the cell 49 10512874
2016 Crystal structures of MBP fusion proteins. Protein science : a publication of the Protein Society 48 26682969
2011 Heterogeneous nuclear ribonucleoprotein (hnRNP) F is a novel component of oligodendroglial RNA transport granules contributing to regulation of myelin basic protein (MBP) synthesis. The Journal of biological chemistry 48 22128153
1999 MBP1: a novel mutant p53-specific protein partner with oncogenic properties. Oncogene 48 10380882
2017 Design of an expression system to enhance MBP-mediated crystallization. Scientific reports 47 28112203
2016 Regulatory and junctional proteins of the blood-testis barrier in human Sertoli cells are modified by monobutyl phthalate (MBP) and bisphenol A (BPA) exposure. Toxicology in vitro : an international journal published in association with BIBRA 47 26922907
2015 Aggregation of MBP in chronic demyelination. Annals of clinical and translational neurology 47 26273684
1986 Isolation and characterization of a cDNA coding for a novel human 17.3K myelin basic protein (MBP) variant. Journal of neuroscience research 46 2427738
2013 Downregulation of tumor suppressor MBP-1 by microRNA-363 in gastric carcinogenesis. Carcinogenesis 44 23975832
2006 Evidence for an association between mannose-binding lectin 2 (MBL2) gene polymorphisms and pre-term birth. Genetics in medicine : official journal of the American College of Medical Genetics 44 16912583
1998 Cloning and sequencing of a cDNA encoding chicken mannan-binding lectin (MBL) and comparison with mammalian analogues. Immunology 43 9640255
2021 The ambiguous role of mannose-binding lectin (MBL) in human immunity. Open medicine (Warsaw, Poland) 42 33681468
2010 APOE epsilon4 and MBL-2 O/O genotypes are associated with neurocognitive impairment in HIV-infected plasma donors. AIDS (London, England) 42 20442634
2001 Mannan-binding lectin (MBL) gene polymorphisms in ulcerative colitis and Crohn's disease. Genes and immunity 42 11607788
2009 MBP-1 suppresses growth and metastasis of gastric cancer cells through COX-2. Molecular biology of the cell 41 19846662
2003 Biochemistry and genetics of mannan-binding lectin (MBL). Biochemical Society transactions 41 12887296
2000 Treatment of experimental allergic encephalomyelitis (EAE) by a rationally designed cyclic analogue of myelin basic protein (MBP) epitope 72-85. Bioorganic & medicinal chemistry letters 40 11133075
1988 Gene organization and transcription of duplicated MBP genes of myelin deficient (shi(mld)) mutant mouse. The EMBO journal 37 2452084
2007 Lung cancer survival and functional polymorphisms in MBL2, an innate-immunity gene. Journal of the National Cancer Institute 35 17848669
2005 Mannose-binding lectin 2 (MBL2) gene polymorphism in asthma and atopy among adults. Clinical and experimental immunology 35 16178865
2014 Transport and translation of MBP mRNA is regulated differently by distinct hnRNP proteins. Journal of cell science 34 24522184
2021 Status of mannose-binding lectin (MBL) and complement system in COVID-19 patients and therapeutic applications of antiviral plant MBLs. Molecular and cellular biochemistry 33 33745077
2000 Mannan-binding lectin (MBL) in chickens: molecular and functional aspects. Developmental and comparative immunology 33 10717281
1998 Golli-MBP gene in multiple sclerosis susceptibility. Journal of neuroimmunology 33 9521617
2004 Increased expression of the MBP mRNA binding protein HnRNP A2 during oligodendrocyte differentiation. Journal of neuroscience research 32 14991837
2003 Purification of functional RNA-protein complexes using MS2-MBP. Current protocols in molecular biology 32 18265330
1998 Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99. International immunology 32 9723700
2014 Restoration of MBL-deficiency: redefining the safety, efficacy and viability of MBL-substitution therapy. Molecular immunology 31 25044097
2009 Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset. Human reproduction (Oxford, England) 29 19491204
2010 MBP-1 is efficiently encoded by an alternative transcript of the ENO1 gene but post-translationally regulated by proteasome-dependent protein turnover. The FEBS journal 27 20849415
2005 Mannose-binding lectin (MBL) and vascular complications in diabetes. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 27 15918118
2017 Characterization of BRPMBL, the Bleomycin Resistance Protein Associated with the Carbapenemase NDM. Antimicrobial agents and chemotherapy 26 28069656
2013 MBL2 gene polymorphisms and susceptibility to tuberculosis in a northeastern Brazilian population. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 26 23524205
2022 Progression and survival of MBL: a screening study of 10 139 individuals. Blood 25 35969843
2019 A Rare Genetic Defect of MBL2 Increased the Risk for Progression of IgA Nephropathy. Frontiers in immunology 25 30967869
2014 Serum MASP-1 in complex with MBL activates endothelial cells. Molecular immunology 25 24472859
2008 MBL2 and MASP2 gene polymorphisms in patients with hepatocellular carcinoma. Journal of viral hepatitis 25 18221301
2006 Tumor-suppressive effects of MBP-1 in non-small cell lung cancer cells. Cancer research 25 17178888
2005 Structural requirements for binding of myelin basic protein (MBP) peptides to MHC II: effects on immune regulation. Current medicinal chemistry 25 15974985
2006 Mannan-binding lectin (MBL) in women with tumours of the reproductive system. Cancer immunology, immunotherapy : CII 24 17131120
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
2022 Fasciola hepatica is refractory to complement killing by preventing attachment of mannose binding lectin (MBL) and inhibiting MBL-associated serine proteases (MASPs) with serpins. PLoS pathogens 22 35007288
2014 If there is an evolutionary selection pressure for the high frequency of MBL2 polymorphisms, what is it? Clinical and experimental immunology 22 24255984
2012 Gfi-1 inhibits the expression of eosinophil major basic protein (MBP) during G-CSF-induced neutrophilic differentiation. International journal of hematology 22 22552881
2010 Association of variant alleles of MBL2 gene with vasoocclusive crisis in children with sickle cell anemia. Blood cells, molecules & diseases 22 20172753
2016 Association of MBL2 Gene Polymorphism with Dental Caries in Saudi Children. Caries research 21 27894112
2015 Affinity Purification of a Recombinant Protein Expressed as a Fusion with the Maltose-Binding Protein (MBP) Tag. Methods in enzymology 21 26096500
2010 SEDLIN forms homodimers: characterisation of SEDLIN mutations and their interactions with transcription factors MBP1, PITX1 and SF1. PloS one 21 20498720
2010 Copper uptake induces self-assembly of 18.5 kDa myelin basic protein (MBP). Biophysical journal 21 21044600
2016 A Meta-analysis of MBL2 Polymorphisms and Tuberculosis Risk. Scientific reports 20 27876780
2015 Cellular stress induces cap-independent alpha-enolase/MBP-1 translation. FEBS letters 20 26144282
2010 Resistance of MBL gene-knockout mice to experimental systemic aspergillosis. Immunology letters 20 20064561
2009 Inhibition of calpain attenuates encephalitogenicity of MBP-specific T cells. Journal of neurochemistry 20 19627443
2000 Kinetic profiles of cerebrospinal fluid anti-MBP in response to intravenous MBP synthetic peptide DENP(85)VVHFFKNIVTP(96)RT in multiple sclerosis patients. Multiple sclerosis (Houndmills, Basingstoke, England) 20 11064438
1990 Suppression of experimental allergic encephalomyelitis by MBP-coupled lymphoid cells and by MBP-liposomes: a comparison. Cellular immunology 20 1691689
2020 Effect of Cholesterol and Myelin Basic Protein (MBP) Content on Lipid Monolayers Mimicking the Cytoplasmic Membrane of Myelin. Cells 19 32106542
2002 MBP-1 mediated apoptosis involves cytochrome c release from mitochondria. Oncogene 19 11973636
2012 Mutations of complement lectin pathway genes MBL2 and MASP2 associated with placental malaria. Malaria journal 18 22380611
1998 Failure of central nervous system myelination in MBP/c-myc transgenic mice: evidence for c-myc cytotoxicity. Oncogene 18 9572493
2017 Acanthamoeba-mediated cytopathic effect correlates with MBP and AhLBP mRNA expression. Parasites & vectors 17 29282148
2014 Expression, purification and thermostability of MBP-chondroitinase ABC I from Proteus vulgaris. International journal of biological macromolecules 17 25077839
2013 Chicken mannose-binding lectin (MBL) gene variants with influence on MBL serum concentrations. Immunogenetics 17 23455474
2012 Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets. American journal of hematology 17 22685020
2017 Variation within MBP gene predicts disease course in multiple sclerosis. Brain and behavior 16 28413712
2017 Frontline Science: Eosinophil-deficient MBP-1 and EPX double-knockout mice link pulmonary remodeling and airway dysfunction with type 2 inflammation. Journal of leukocyte biology 16 28515227
2015 Interaction of human mannose-binding lectin (MBL) with Yersinia enterocolitica lipopolysaccharide. International journal of medical microbiology : IJMM 16 26188838
2013 Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer. BMC cancer 16 23421821
2012 Genetic variants of the MBL2 gene are associated with mortality in pneumococcal sepsis. Diagnostic microbiology and infectious disease 16 22578937
2010 Mannose binding lectin (MBL) in autoimmunity and its role in systemic lupus erythematosus (SLE). The Journal of the Association of Physicians of India 16 21510462
2009 Genetic and structural analysis of MBL2 and MASP2 polymorphisms in south-eastern African children. Tissue antigens 16 19775369
2008 Mannan-binding lectin (MBL) polymorphism and gastric cancer risk in Japanese population. Digestive diseases and sciences 16 18368489
2012 Association between bronchopulmonary dysplasia and MBL2 and IL1-RN polymorphisms. Pediatrics international : official journal of the Japan Pediatric Society 15 22882323
2011 Mannan-binding lectin (MBL) and MBL-associated serine protease-2 in children with cancer. Swiss medical weekly 15 21528466