Affinage

MBP

Myelin basic protein · UniProt P02686

Round 2 corrected
Length
304 aa
Mass
33.1 kDa
Annotated
2026-04-28
130 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Myelin basic protein (MBP) is an intrinsically disordered, membrane-associated protein essential for compaction of the myelin sheath in the central nervous system, where it zips together cytoplasmic leaflets of oligodendrocyte membranes in a process counterbalanced by CNP-mediated cytoskeletal organization of cytoplasmic nanochannels (PMID:28076777, PMID:9373033). MBP mRNA is transported from the oligodendrocyte soma to the myelin sheath in RNA granules containing hnRNP A2 and hnRNP F via a dynein/dynactin-dependent mechanism; local translation is controlled by a molecular switch in which inhibitory hnRNP-E1 is displaced by stimulatory hnRNP-K, with Fyn kinase phosphorylation releasing hnRNP F to derepress translation (PMID:29073112, PMID:22128153, PMID:24522184). Post-translational citrullination renders MBP susceptible to MMP-3 cleavage, releasing immunodominant epitopes relevant to autoimmune demyelination, and divalent cations (Cu²⁺, Zn²⁺) promote MBP self-assembly in vitro, suggesting additional levels of regulation of myelin compaction (PMID:16871440, PMID:21044600). The MBP gene also encodes Golli isoforms expressed in lymphoid and neural tissues; T cells reactive to specific MBP epitopes (including exon 2-encoded and 83–99 peptides) are encephalitogenic in experimental autoimmune encephalomyelitis models, and the unusually weak binding of MBP peptides to MHC class II (I-Aᵘ) explains incomplete central tolerance to this self-antigen (PMID:12150894, PMID:7512579).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1986 Medium

    Cloning of a human 17.3 kDa MBP cDNA variant revealed species-specific alternative splicing of the MBP gene, establishing that multiple MBP isoforms arise from differential exon usage rather than separate genes.

    Evidence cDNA library screening and sequence analysis from human fetal spinal cord

    PMID:2427738

    Open questions at the time
    • Functional significance of individual splice variants was not tested
    • Tissue-specific expression patterns of each isoform remained unresolved
  2. 1988 Medium

    Analysis of the shiverer-mld duplication showed that reduced MBP expression in this dysmyelinating mutant is not caused by intrinsic promoter defects but by the genomic rearrangement itself, focusing attention on structural and regulatory features of the MBP locus.

    Evidence In vitro run-off transcription comparing duplicated MBP gene promoters from shi(mld) mice

    PMID:2452084

    Open questions at the time
    • Exact mechanism by which the gene inversion silences MBP was not identified
    • In vitro assay in HeLa extracts may not recapitulate oligodendrocyte-specific regulation
  3. 1993 Medium

    Identification of a 256 bp proximal promoter sufficient for oligodendrocyte-specific expression established the minimal cis-regulatory architecture of MBP transcription and confirmed that MBP mRNA is restricted to the cell body, implicating post-transcriptional transport.

    Evidence Transgenic mice carrying MBP promoter-lacZ constructs with histochemical validation

    PMID:7505168

    Open questions at the time
    • Distal enhancers and chromatin context were not tested
    • Trans-acting factors binding this promoter were not identified in this study
  4. 1997 Medium

    The competing activator MEF-1/Pur alpha and repressor MyEF-2 were shown to bind overlapping sites in the MBP proximal promoter, providing a molecular mechanism for transcriptional regulation of MBP in oligodendrocytes.

    Evidence EMSA with purified recombinant proteins and competitive binding assays on MB1 element

    PMID:9282330

    Open questions at the time
    • In vivo relevance not demonstrated by chromatin immunoprecipitation or genetic perturbation
    • Signaling inputs controlling MEF-1/MyEF-2 balance were unknown
  5. 1997 High

    CNP overexpression in transgenic mice showed that CNP displaces MBP from myelin lamellae, establishing the principle that compact myelin composition is determined by competitive interactions between MBP and CNP — not simply by MBP abundance alone.

    Evidence Transgenic mouse overexpressing CNP 6-fold, electron microscopy and immunohistochemistry

    PMID:9373033

    Open questions at the time
    • Direct physical interaction between CNP and MBP was not demonstrated
    • Loss-of-function complement (CNP knockout) was not reported here
  6. 1998 High

    Mutagenesis of I-Aᵘ and MBP Ac1-9 revealed that Lys-4 buried in the hydrophobic P6 pocket accounts for the exceptionally weak MHC binding of MBP, explaining why central tolerance fails to eliminate MBP-reactive T cells — a key insight for understanding autoimmune demyelination.

    Evidence Site-directed mutagenesis, synthetic peptide binding and T-cell activation assays

    PMID:9565642

    Open questions at the time
    • Applicability to human HLA-DR alleles was not addressed
    • Whether other MBP epitopes share similar weak-anchor mechanisms was unknown
  7. 2002 High

    QKI RNA-binding proteins were identified as essential regulators of MBP mRNA nuclear export; loss of QKI function in quaking mice traps MBP mRNA in the nucleus, directly linking RNA-binding protein dysfunction to hypomyelination.

    Evidence Retroviral QKI expression, in situ hybridization, subcellular fractionation in oligodendrocytes and qkv mouse brain

    PMID:12467586

    Open questions at the time
    • Direct RNA-binding sites on MBP mRNA for QKI were not mapped
    • Relationship between QKI and hnRNP-mediated cytoplasmic transport was unclear
  8. 2002 High

    The crystal structure of I-Aᵘ/MBP1-11 at 2.2 Å confirmed that only residues 1–7 occupy the peptide groove and that Lys-4 occupancy of the P6 pocket is structurally unfavorable, providing atomic-level understanding of autoreactive T-cell escape from tolerance.

    Evidence X-ray crystallography with mutagenesis and T-cell activation validation

    PMID:12150894

    Open questions at the time
    • No structure of MBP peptide with human HLA class II was determined
    • In vivo thymic selection dynamics were not directly measured
  9. 2004 Medium

    Post-translational modifications of hnRNP A2 — methylation and CK2-mediated phosphorylation — were shown to control its nuclear-to-cytoplasmic redistribution and hence the transport of MBP mRNA granules into oligodendrocyte processes.

    Evidence Pharmacological inhibition (AdOx, DRB) in oligodendrocyte cultures with subcellular fractionation and in situ hybridization

    PMID:14991837

    Open questions at the time
    • Pharmacological inhibitors are not specific to hnRNP A2; genetic validation was lacking
    • Specific modification sites on hnRNP A2 were not mapped
  10. 2006 Medium

    Citrullination of MBP (the component-8 charge isomer elevated in MS) was shown to render MBP highly susceptible to MMP-3 proteolysis even within intact myelin, releasing immunodominant peptides — linking post-translational modification to autoimmune epitope generation.

    Evidence In vitro proteolysis kinetics comparing citrullinated vs. non-citrullinated MBP isoforms, including lipid-containing systems

    PMID:16871440

    Open questions at the time
    • In vivo relevance of MMP-3 cleavage of citrullinated MBP in MS lesions was not demonstrated
    • Upstream regulation of citrullination was not addressed
  11. 2011 High

    hnRNP F was identified as a new translational repressor component of MBP mRNA granules, whose Fyn kinase-dependent phosphorylation and release from mRNA derepresses MBP translation — revealing the kinase-triggered step in local translation control.

    Evidence Co-immunoprecipitation, RNA immunoprecipitation, and Fyn kinase activation assays in primary oligodendrocytes

    PMID:22128153

    Open questions at the time
    • Specific phosphorylation sites on hnRNP F were not identified
    • Whether Fyn acts directly on hnRNP F or through intermediary kinases was unresolved
  12. 2014 High

    Dissection of hnRNP roles resolved that hnRNP A2 mediates transport but not translational inhibition, while hnRNP E1 and hnRNP K function as an inhibitor–activator switch on the MBP 3′-UTR, establishing a complete model of coupled transport and translational control.

    Evidence 3′-UTR deletion/mutation analysis, overexpression and knockdown, myelin sheet growth assays in oligodendrocyte cultures

    PMID:24522184

    Open questions at the time
    • Signals triggering E1-to-K exchange in vivo were not identified
    • Stoichiometry and structural basis of the hnRNP switch on the 3′-UTR were not determined
  13. 2017 High

    MBP-driven membrane compaction and CNP-organized actin cytoskeleton were shown to constitute opposing forces that together control cytoplasmic nanochannel architecture in compact myelin, unifying earlier observations into a biomechanical model of myelin ultrastructure.

    Evidence High-pressure freezing EM, genetic knockout/overexpression models in mice

    PMID:28076777

    Open questions at the time
    • How the MBP/CNP balance is developmentally regulated was not determined
    • Whether other myelin proteins contribute to the force balance was not addressed
  14. 2017 High

    A forward genetic screen identified the dynein/dynactin motor complex as essential for bidirectional MBP mRNA granule transport in oligodendrocytes, resolving the paradox of how a retrograde motor drives anterograde mRNA delivery to the myelin sheath.

    Evidence Zebrafish genetic screen (actr10 mutant), biochemical granule isolation from mammalian oligodendrocytes, live-cell imaging with pharmacological dynein inhibition

    PMID:29073112

    Open questions at the time
    • The anterograde motor partner (presumably kinesin) was not identified
    • Mechanism coupling retrograde motor to anterograde movement was not resolved
  15. 2020 Medium

    Systematic variation of cholesterol content in reconstituted membranes demonstrated that the native 44 mol% cholesterol of the cytoplasmic myelin leaflet is optimal for MBP–membrane interaction and compaction, indicating that lipid composition is a critical determinant of MBP function.

    Evidence Langmuir monolayer experiments with systematic cholesterol variation and fluorescence microscopy

    PMID:32106542

    Open questions at the time
    • In vivo validation in oligodendrocytes with altered cholesterol levels was not performed
    • Whether cholesterol effects are direct or mediated by membrane fluidity changes was not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of MBP's intrinsically disordered membrane-compacting activity, the signaling cascade that coordinates hnRNP E1-to-K exchange for local translation activation, and the in vivo mechanism coupling dynein-dependent transport to site-specific translational derepression remain unresolved.
  • No high-resolution structure of membrane-bound MBP exists
  • In vivo signaling upstream of the hnRNP translational switch is uncharacterized
  • Mechanism by which dynein/dynactin achieves bidirectional mRNA granule movement is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008289 lipid binding 3
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 2
Pathway
GO:0005886 plasma membrane 1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase) directly associates with and organizes the actin cytoskeleton in oligodendrocytes, providing an intracellular strut that counteracts membrane compaction by MBP. CNP is essential for generating and maintaining cytoplasmic nanochannels within compact myelin, opposing MBP-driven membrane compaction. High-pressure freezing electron microscopy, genetic knockout and overexpression models in mice, co-localization and functional analysis of CNP and MBP in myelin compartments Cell reports High 28076777
2002 The QKI RNA-binding proteins regulate the nuclear export of MBP mRNAs in oligodendrocytes. Disruption of the QKI nucleocytoplasmic equilibrium causes nuclear and perikaryal retention of MBP mRNAs, preventing their export to cytoplasmic processes, thereby reducing MBP protein levels and impairing myelination (as observed in quaking viable mice). Retroviral expression of QKI isoforms, in situ hybridization, subcellular fractionation and RNA analysis in oligodendrocytes and qkv mouse brain Neuron High 12467586
1997 CNP overexpression in transgenic mice inhibits MBP accumulation and myelin compaction. Myelin lamellae lacking major dense lines (compacted by MBP) are deficient in MBP and enriched in CNP, indicating that CNP can compete with or displace MBP from compact myelin domains, and that CNP may help target MBP to compact myelin. Transgenic mouse overexpressing CNP (6-fold), electron microscopy, immunohistochemical co-localization of CNP and MBP in myelin membranes Journal of neuroscience research High 9373033
2008 MMP-9 regulates the initial Schwann cell-mediated processing/degradation of myelin basic protein after spinal nerve crush injury. MMPs (particularly MMP-9) selectively degrade MBP, promoting mechanical allodynia; broad-spectrum MMP inhibition with GM6001 protected against MBP degradation and attenuated mechanical nociception. MMP-9 knockout mice, L5 spinal nerve crush model, GM6001 pharmacological inhibition, immunohistochemistry and immunoblotting for MBP degradation products Molecular and cellular neurosciences High 18817874
2002 The crystal structure of the I-Au MHC class II/MBP1-11 complex (2.2 Å) revealed that only MBP residues 1-7 are bound toward one end of the peptide-binding cleft. The key MBP residue Lys-4 is buried in the P6 pocket of I-Au (which is predominantly hydrophobic), explaining the unusually short half-life of the complex and why mice are not tolerant to this self-peptide. X-ray crystallography at 2.2 Å resolution of I-Au/MBP1-11 complex; mutagenesis of I-Au and MBP peptides; biochemical and T-cell activation assays Immunity High 12150894
2017 The retrograde motor complex dynein/dynactin is paradoxically required for anterograde transport of Mbp mRNA in oligodendrocytes. Mbp mRNA granules physically associate with the retrograde motor complex. Acute pharmacological dynein inhibition arrests Mbp mRNA transport in both directions; chronic inhibition abolishes Mbp mRNA distribution and dramatically decreases MBP protein levels. Forward genetic screen in zebrafish identifying actr10 (Arp11/dynactin subunit) mutation; biochemical isolation of reporter-tagged Mbp mRNA granules from mammalian oligodendrocytes; live-cell imaging with pharmacological dynein inhibition; in vivo myelination assays Proceedings of the National Academy of Sciences of the United States of America High 29073112
2011 hnRNP F is a novel component of MBP mRNA transport granules in oligodendrocytes, associated with hnRNP A2 and MBP mRNA in cytoplasmic granular structures. Fyn kinase activation leads to phosphorylation of hnRNP F in the cytoplasm and its release from MBP mRNA and RNA granules, thereby derepressing MBP translation. Co-immunoprecipitation, immunofluorescence co-localization, RNA immunoprecipitation, Fyn kinase activation assays, phosphorylation analysis in primary oligodendrocytes The Journal of biological chemistry High 22128153
2014 hnRNP A2 mediates MBP mRNA transport but not translational inhibition; hnRNP E1 inhibits MBP translation while hnRNP K promotes it. These factors share binding sites within the 3'-UTR of MBP mRNA, and translation is activated by exchange of inhibitory hnRNP-E1 for stimulatory hnRNP-K within the mRNP complex. Identification of 3'-UTR regulatory regions by deletion/mutation analysis; RNA-protein binding assays; overexpression and knockdown of hnRNP A2, K, and E1; myelin sheet growth assays in oligodendrocyte cultures Journal of cell science High 24522184
2006 Citrullinated MBP charge isomer (component-8), whose levels are elevated in multiple sclerosis brain, is more susceptible to cleavage by stromelysin-1 (MMP-3) than the non-citrullinated component-1 isoform. MMP-3 can cleave MBP in the presence of lipids and within intact myelin, releasing peptides containing the immunodominant epitope. In vitro proteolysis assays comparing citrullinated (component-8) vs. non-citrullinated (component-1) MBP isoforms; kinetic digestion analysis; assays in lipid-containing systems and intact myelin Neurochemical research Medium 16871440
2002 Transferrin selectively regulates MBP gene expression at the transcriptional level (run-off transcription assay in oligodendrocytes shows increased MBP mRNA at the nuclear level), without affecting PLP transcription. In combination with IGF-1, transferrin synergizes to profoundly enhance myelinogenesis in myelin-deficient rats. In vivo injections in myelin-deficient (md) rats; oligodendrocyte cultures; nuclear run-off transcription assays; in situ hybridization; immunofluorescence Developmental neuroscience Medium 12401963
1986 A human 17.3K MBP cDNA variant was isolated and characterized; it lacks two sequences (exons 2 and 5) found in mouse 17K MBP and contains exon 6 absent in the mouse variant, indicating that the primary splicing pathway of the human MBP gene differs from that of the mouse. The human 17.3K variant is identical to the 18.5K MBP except for deletion of an 11-amino-acid peptide including the single tryptophan residue. cDNA library construction and screening; sequence analysis; in vitro translation of human fetal spinal cord poly A(+) mRNA Journal of neuroscience research Medium 2427738
1998 Site-directed mutagenesis of I-Au and the MBP Ac1-9 peptide demonstrated that Lys-4 of MBP is the key residue for MHC binding, buried in the P6 pocket of I-Au, leaving the N-terminal region of the MHC cleft unoccupied. Extension of the MBP peptide N-terminus by 6 amino acids and replacement of Lys in the P6 pocket with an aromatic anchor increased binding stability more than 1,000-fold. Site-directed mutagenesis of I-Au; synthetic peptide binding assays; T-cell activation assays; molecular modeling The Journal of experimental medicine High 9565642
1993 A 256 bp proximal fragment of the mouse MBP promoter is sufficient to direct oligodendroglial-specific expression of a lacZ transgene in vivo, indicating that cis-acting regulatory elements specifying oligodendrocyte identity reside within this region. The MBP-lacZ mRNA was confined to the oligodendrocyte cell body, consistent with post-transcriptional targeting of MBP protein to the myelin sheath. Transgenic mice carrying MBP promoter-lacZ constructs; histochemical and immunohistochemical analysis of beta-galactosidase expression; in situ hybridization The European journal of neuroscience Medium 7505168
1988 In shi(mld) mice the MBP gene is duplicated; in vitro run-off assays using HeLa whole-cell extracts showed that the 1.3 kb 5'-flanking regions of both duplicated MBP genes have the same promoter activity as the control MBP gene, indicating that reduced MBP expression in shi(mld) is not due to intrinsic promoter activity differences but to other regulatory mechanisms (possibly the gene inversion). Restriction mapping, chromosomal in situ hybridization, in vitro run-off transcription assays with HeLa extracts The EMBO journal Medium 2452084
2004 hnRNP A2, the trans-acting factor mediating intracellular trafficking of MBP mRNA, undergoes increased cytoplasmic (granular) redistribution as oligodendrocytes differentiate into MBP-positive cells. Inhibition of methylation (by AdOx) or CK2-mediated phosphorylation (by DRB) maintains hnRNP A2 in a predominantly nuclear distribution and blocks RNA trafficking granules from entering processes. Pharmacological inhibition of methylation (AdOx) and CK2 (DRB) in oligodendrocyte cultures; subcellular fractionation; immunofluorescence; in situ hybridization for MBP mRNA Journal of neuroscience research Medium 14991837
2010 QKI-6 co-localizes with Ago2 (a component of the RISC complex) and MBP mRNA in cytoplasmic stress granules of glial cells. Co-immunoprecipitation demonstrated an interaction between QKI-6 and Ago2, identifying QKI-6 as a new stress granule component in oligodendrocytes. Co-immunoprecipitation of QKI-6 and Ago2; immunofluorescence co-localization with stress granule markers and MBP mRNA; arsenite-induced stress granule formation in glial cells PloS one Medium 20862255
2010 MBP (18.5 kDa) specifically coordinates two Cu2+ atoms or one Zn2+ atom per molecule in solution. Above a threshold of four Cu2+ or two Zn2+ atoms per MBP molecule (in the presence of phosphates), large MBP aggregates form, suggesting that divalent cations can mediate MBP-MBP interactions relevant to myelin sheath formation and stabilization. Continuous wave and pulse EPR (electron paramagnetic resonance) spectroscopy; dynamic light scattering; metal binding titration experiments with purified bovine MBP Biophysical journal Medium 21044600
2014 MBP and myelin protein P2 act synergistically to influence the structure of reconstituted myelin membranes. Although neither protein alone significantly alters membrane dynamics (pico- to nanosecond lipid motions), together they markedly affect membrane lamellar spacing and organization, consistent with MBP's role in membrane compaction. Neutron diffraction and quasi-elastic neutron scattering (QENS) of reconstituted multilamellar myelin membranes with and without MBP and P2 Soft matter Medium 24651633
1997 MEF-1/Pur alpha, an activator protein binding the MB1 regulatory motif (-14 to -50) in the MBP promoter, directly inhibits the binding of the repressor MyEF-2 to the same region by competing for the same or overlapping binding site. Conversely, MyEF-2 enhances the dimeric association of MEF-1/Pur alpha with MB1 DNA. Two distinct regions of MEF-1/Pur alpha are involved in both its DNA binding and its ability to block MyEF-2. Electrophoretic mobility shift assays (EMSA) with purified recombinant MEF-1/Pur alpha and MyEF-2 proteins; MEF-1/Pur alpha variant analysis; competitive binding assays Journal of cellular biochemistry Medium 9282330
2006 Hsp70 purified from normal appearing white matter of both MS and normal human brain is specifically associated with immunodominant MBP peptides. Hsp70-MBP peptide complexes prepared in vitro are highly immunogenic and have adjuvant-like effects, stimulating MBP peptide-specific T cell lines to respond to normally sub-optimal concentrations of peptide. Hsp70 purification from human brain white matter; co-purification with MBP peptides; in vitro reconstitution of Hsp70-MBP peptide complexes; T-cell stimulation assays Journal of the neurological sciences Medium 16842822
2015 MBP undergoes prion-like aggregation within oligodendrocytes and around neuronal cells during chronic demyelination (cuprizone model and chronic EAE). In chronic EAE, MBP co-precipitates with Tau. Lipid composition analysis of brain membranes in chronic EAE reveals altered lipid rafts that may prevent appropriate insertion and compaction of new MBP, causing its misfolding and aggregation. Triton X-100 flotation gradient fractionation to assess lipid raft composition; immunoprecipitation for MBP and Tau co-precipitation; immunohistochemistry in cuprizone and chronic EAE mouse models Annals of clinical and translational neurology Medium 26273684
2020 The native cholesterol content (44 mol%) of the cytoplasmic myelin leaflet represents an optimum for both membrane order (correlating with compaction) and MBP interaction with lipid monolayers. Varying cholesterol content from 0% to 100% demonstrates that MBP insertion into and interaction with membranes is highly dependent on cholesterol concentration. Langmuir lipid monolayer experiments with Langmuir trough; fluorescence microscopy of lipid monolayers; systematic variation of cholesterol content with and without MBP Cells Medium 32106542
2021 Traumatic brain injury triggers proteolytic processing of MBP, releasing specific low-molecular-weight peptides including TQDENPVVHFF and TQDENPVVHF (C-terminal MBP peptides) that are elevated in acute and subacute TBI cerebrospinal fluid. MBP and Golli-MBP are processed to protein breakdown products (BDPs) and proteolytic peptides after TBI. Ultrafiltration-based peptide enrichment of CSF; nano-LC/MS-MS peptidomics; MS/MS selected reaction monitoring; immunoblotting for MBP protein breakdown products in human TBI CSF vs. controls Molecular neurobiology Medium 34762230
1994 T lymphocytes sensitized to the exon 2-encoded peptide of MBP (not present in the abundant 18.5 kDa isoform) are encephalitogenic in SJL mice; the disease can be induced by adoptive transfer of exon 2-reactive lymphocytes. The immunodominant epitope localizes to amino acids 59-85 of the exon 2 peptide. Immunization of SJL/J mice with MBP exon 2 peptide; adoptive transfer of exon 2-sensitized lymphocytes; histological assessment of EAE; epitope mapping with overlapping peptides Journal of neuroimmunology Medium 7512579
1996 Human T-cell clones specific for the immunodominant MBP 83-99 epitope cross-react with golli MBP isoforms (HOG 7) expressed in lymphoid tissues. Ten of 12 T-cell clones recognized golli MBP, although the response to classic MBP was greater, suggesting differences in antigen processing between the two isoforms. T-cell clones generated from human PBMCs; T-cell proliferation and cytotoxicity assays with classic MBP and golli MBP; HLA restriction analysis; TCR usage determination Journal of neuroscience research Low 8892094
2001 The MBP gene encodes non-classic MBP gene products (Golli proteins) that appear to be components of transcriptional complexes in the nucleus and may be involved in signaling pathways in T-cells and neural cells, demonstrating functions for MBP gene products beyond structural myelin compaction. Review synthesizing data from naturally-occurring mutations (shiverer, myelin-deficient rats) and transgenic mice; biochemical and cell biological studies of Golli-MBP localization and function Brain pathology (Zurich, Switzerland) Low 11145205

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
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
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
2001 The pathobiology of myelin mutants reveal novel biological functions of the MBP and PLP genes. Brain pathology (Zurich, Switzerland) 109 11145205
2010 MBP-1 upregulates miR-29b that represses Mcl-1, collagens, and matrix-metalloproteinase-2 in prostate cancer cells. Genes & cancer 105 20657750
2008 MMPs initiate Schwann cell-mediated MBP degradation and mechanical nociception after nerve damage. Molecular and cellular neurosciences 97 18817874
2015 Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation. Molecular cell 94 25728769
2002 Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of MBP complexed with I-Au. Immunity 86 12150894
2001 Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England) 78 11724443
2002 Antagonistic effects of human cyclic MBP(87-99) altered peptide ligands in experimental allergic encephalomyelitis and human T-cell proliferation. Journal of medicinal chemistry 73 11784132
2010 Hypoxia induces differential translation of enolase/MBP-1. BMC cancer 72 20412594
1997 CNP overexpression induces aberrant oligodendrocyte membranes and inhibits MBP accumulation and myelin compaction. Journal of neuroscience research 72 9373033
1994 Binding of human collectins (SP-A and MBP) to influenza virus. The Biochemical journal 72 7998980
1992 Activation of protein serine/threonine kinases p42, p63, and p87 in Rous sarcoma virus-transformed cells: signal transduction/transformation-dependent MBP kinases. Molecular biology of the cell 70 1337288
2019 Monobutyl phthalate (MBP) can dysregulate the antioxidant system and induce apoptosis of zebrafish liver. Environmental pollution (Barking, Essex : 1987) 61 31761585
1995 Human breast carcinoma cells transfected with the gene encoding a c-myc promoter-binding protein (MBP-1) inhibits tumors in nude mice. Cancer research 59 7641187
2008 The activated Notch1 receptor cooperates with alpha-enolase and MBP-1 in modulating c-myc activity. Molecular and cellular biology 58 18490439
1995 The Gly-54-->Asp allelic form of human mannose-binding protein (MBP) fails to bind MBP-associated serine protease. The Biochemical journal 56 7487919
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
2017 Dynein/dynactin is necessary for anterograde transport of Mbp mRNA in oligodendrocytes and for myelination in vivo. Proceedings of the National Academy of Sciences of the United States of America 52 29073112
2005 Expression of MBP, PLP, MAG, CNP, and GFAP in the Human Alcoholic Brain. Alcoholism, clinical and experimental research 50 16205370
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
1995 The c-myc promoter binding protein (MBP-1) and TBP bind simultaneously in the minor groove of the c-myc P2 promoter. Biochemistry 48 7880838
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
2006 MBP-PLP fusion protein-induced EAE in C57BL/6 mice. Journal of neuroimmunology 46 16781782
2006 Differences in susceptibility of MBP charge isomers to digestion by stromelysin-1 (MMP-3) and release of an immunodominant epitope. Neurochemical research 46 16871440
2002 Transferrin regulates transcription of the MBP gene and its action synergizes with IGF-1 to enhance myelinogenesis in the md rat. Developmental neuroscience 46 12401963
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
1998 Evidence that the autoimmune antigen myelin basic protein (MBP) Ac1-9 binds towards one end of the major histocompatibility complex (MHC) cleft. The Journal of experimental medicine 42 9565642
1993 The proximal region of the MBP gene promoter is sufficient to induce oligodendroglial-specific expression in transgenic mice. The European journal of neuroscience 42 7505168
2009 MBP-1 suppresses growth and metastasis of gastric cancer cells through COX-2. Molecular biology of the cell 41 19846662
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
2015 Positional effects of fusion partners on the yield and solubility of MBP fusion proteins. Protein expression and purification 39 25782741
2000 Treatment of experimental allergic encephalomyelitis (EAE) induced by guinea pig myelin basic protein epitope 72-85 with a human MBP(87-99) analogue and effects of cyclic peptides. Bioorganic & medicinal chemistry 39 11003134
2005 Proteinase inhibition by proform of eosinophil major basic protein (pro-MBP) is a multistep process of intra- and intermolecular disulfide rearrangements. The Journal of biological chemistry 38 15647258
2018 Estrogenic Mechanisms and Cardiac Responses Following Early Life Exposure to Bisphenol A (BPA) and Its Metabolite 4-Methyl-2,4-bis( p-hydroxyphenyl)pent-1-ene (MBP) in Zebrafish. Environmental science & technology 37 29738667
2004 Unique clinical and pathological features in HLA-DRB1*0401-restricted MBP 111-129-specific humanized TCR transgenic mice. The Journal of experimental medicine 37 15263029
1988 Gene organization and transcription of duplicated MBP genes of myelin deficient (shi(mld)) mutant mouse. The EMBO journal 37 2452084
1997 Appearance of 1-2 Mbp giant DNA fragments as an early common response leading to cell death induced by various substances that cause oxidative stress. Free radical biology & medicine 35 9165301
1995 Collectin in a non-mammalian species: isolation and characterization of mannan-binding protein (MBP) from chicken serum. Glycobiology 35 8563142
1994 A high resolution physical map of 2.5 Mbp of the Down syndrome region on chromosome 21. Human molecular genetics 35 7849705
2014 Transport and translation of MBP mRNA is regulated differently by distinct hnRNP proteins. Journal of cell science 34 24522184
1998 Golli-MBP gene in multiple sclerosis susceptibility. Journal of neuroimmunology 33 9521617
2012 Cross-reactivity of autoreactive T cells with MBP and viral antigens in patients with MS. Frontiers in bioscience (Landmark edition) 32 22201827
2008 Retinoic acid-mediated down-regulation of ENO1/MBP-1 gene products caused decreased invasiveness of the follicular thyroid carcinoma cell lines. Journal of molecular endocrinology 32 19060179
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
2007 The dynamics of the MBP-MalFGK(2) interaction: a prototype for binding protein dependent ABC-transporter systems. Biochimica et biophysica acta 31 17950243
2018 Repeated Exposure to 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), an Active Metabolite of Bisphenol A, Aggressively Stimulates Breast Cancer Cell Growth in an Estrogen Receptor β (ERβ)-Dependent Manner. Molecular pharmacology 30 30552153
2008 A double mutation of MBP(83-99) peptide induces IL-4 responses and antagonizes IFN-gamma responses. Journal of neuroimmunology 30 18675465
1994 Experimental allergic encephalomyelitis induced by the peptide encoded by exon 2 of the MBP gene, a peptide implicated in remyelination. Journal of neuroimmunology 30 7512579
2010 The QKI-6 RNA binding protein localizes with the MBP mRNAs in stress granules of glial cells. PloS one 29 20862255
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
1996 Genomic targeting with an MBP-Cre fusion protein. Gene 28 8996087
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
2014 Structural and dynamical properties of reconstituted myelin sheaths in the presence of myelin proteins MBP and P2 studied by neutron scattering. Soft matter 25 24651633
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
2002 Chemokine receptor expression on MBP-reactive T cells: CXCR6 is a marker of IFNgamma-producing effector cells. Journal of neuroimmunology 25 12044980
1998 Preserved epitope-specific T cell activation by recombinant Bet v 1-MBP fusion proteins. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 25 9641568
1993 Increased synthetic peptide specificity of tissue-CSF bound anti-MBP in multiple sclerosis. Journal of neuroimmunology 24 7681451
2011 A systematic assessment of mature MBP in membrane protein production: overexpression, membrane targeting and purification. Protein expression and purification 23 21689756
1997 Evidence for inhibition of MyEF-2 binding to MBP promoter by MEF-1/Pur alpha. Journal of cellular biochemistry 23 9282330
2022 Glycine ameliorates MBP-induced meiotic abnormalities and apoptosis by regulating mitochondrial-endoplasmic reticulum interactions in porcine oocytes. Environmental pollution (Barking, Essex : 1987) 22 35839969
2012 Gfi-1 inhibits the expression of eosinophil major basic protein (MBP) during G-CSF-induced neutrophilic differentiation. International journal of hematology 22 22552881
2015 Affinity Purification of a Recombinant Protein Expressed as a Fusion with the Maltose-Binding Protein (MBP) Tag. Methods in enzymology 21 26096500
2015 Increased expression of NDEL1 and MBP genes in the peripheral blood of antipsychotic-naïve patients with first-episode psychosis. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 21 26476704
2013 Interactions between Golli-MBP and Th1/Th2 cytokines in patients with oral lichen planus. Oral diseases 21 23496331
2010 Copper uptake induces self-assembly of 18.5 kDa myelin basic protein (MBP). Biophysical journal 21 21044600
2007 Are there enhanced MBP autoantibodies in autism? Journal of autism and developmental disorders 21 17588145
2006 Association of MBP peptides with Hsp70 in normal appearing human white matter. Journal of the neurological sciences 21 16842822
2002 Diversity and dynamics of the T-cell response to MBP in DR2+ve individuals. Clinical and experimental immunology 21 12067310
2015 Soluble expression, rapid purification, and characterization of human interleukin-24 (IL-24) using a MBP-SUMO dual fusion system in Escherichia coli. Applied microbiology and biotechnology 20 25681151
2015 Cellular stress induces cap-independent alpha-enolase/MBP-1 translation. FEBS letters 20 26144282
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
2011 Ophthalmopathology in rats with MBP-induced experimental autoimmune encephalomyelitis. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 19 21344308
2002 Cystatin C in milk basic protein (MBP) and its inhibitory effect on bone resorption in vitro. Bioscience, biotechnology, and biochemistry 19 12596844
2018 The Biological Significance and Regulatory Mechanism of c-Myc Binding Protein 1 (MBP-1). International journal of molecular sciences 18 30518090
2009 Association between golli-MBP and schizophrenia in the Jewish Ashkenazi population: are regulatory regions involved? The international journal of neuropsychopharmacology 18 19154657
1996 Human T lymphocytes specific for the immunodominant 83-99 epitope of myelin basic protein: recognition of golli MBP HOG 7. Journal of neuroscience research 18 8892094
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
2014 Myelin Basic Protein and a Multiple Sclerosis-related MBP-peptide Bind to Oligonucleotides. Molecular therapy. Nucleic acids 17 25202925
2021 Generation and Release of Neurogranin, Vimentin, and MBP Proteolytic Peptides, Following Traumatic Brain Injury. Molecular neurobiology 16 34762230
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
2013 Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer. BMC cancer 16 23421821
2016 A 0.5-Mbp deletion on bovine chromosome 23 is a strong candidate for stillbirth in Nordic Red cattle. Genetics, selection, evolution : GSE 15 27091210
2015 Promiscuity of autoimmune responses to MBP after stroke. Journal of neuroimmunology 15 26198925
2006 Golli-MBP copy number analysis by FISH, QMPSF and MAPH in 195 patients with hypomyelinating leukodystrophies. Annals of human genetics 15 16441258
2003 Time course of T-cell responses to MOG and MBP in patients with clinically isolated syndromes. Journal of neuroimmunology 15 12620656
1996 Frequency of MBP and MBP peptide-reactive T cells in the HPRT mutant T-cell population of MS patients. Neurology 15 8628491
2000 Suppression of ongoing experimental allergic encephalomyelitis (EAE) in Lewis rats: synergistic effects of myelin basic protein (MBP) peptide 68-86 and IL-4. Clinical and experimental immunology 14 10844533