Affinage

MTPN

Myotrophin · UniProt P58546

Round 2 corrected
Length
118 aa
Mass
12.9 kDa
Annotated
2026-04-29
130 papers in source corpus 13 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MTPN (myotrophin/V-1) is a small ankyrin-repeat protein that operates in two principal mechanistic contexts: regulation of actin dynamics through direct sequestration of heterodimeric capping protein (CP/CapZ), and initiation of cardiac hypertrophy through PKC–IKKβ–NF-κB signaling. MTPN binds CP with ~120 nM affinity in a 1:1 stoichiometric complex, inhibiting barbed-end capping and thereby suppressing Arp2/3-dependent branched actin assembly; this sequestration activity is regulated by phosphorylation and is present in molar excess over CP in the cytoplasm (PMID:12488317, PMID:27791032). In cardiomyocytes, MTPN stimulates protein synthesis via activation of PKCα and PKCε isoforms, which signal through IKKβ to activate NF-κB, inducing hypertrophic marker genes; cardiac-specific overexpression in mice drives progressive hypertrophy to heart failure, while genetic blockade of NF-κB or shRNA-mediated MTPN silencing reverses hypertrophic remodeling (PMID:9633917, PMID:12486112, PMID:14970239, PMID:18620706, PMID:19502558). The transition from hypertrophy to heart failure requires p53 upregulation, as p53 deletion in myotrophin-transgenic mice attenuates disease progression (PMID:20202977).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1997 High

    Determination of myotrophin's three-dimensional structure revealed a 2.5-ankyrin-repeat scaffold with a dynamically flexible hairpin in the first repeat, establishing the protein-protein interaction architecture that underlies its binding functions.

    Evidence Multidimensional heteronuclear NMR on isotopically labeled recombinant myotrophin

    PMID:9194197

    Open questions at the time
    • No binding partner had yet been mapped onto the ankyrin-repeat surface
    • Functional significance of the flexible hairpin region was unresolved
  2. 1998 High

    Identification of PKCα and PKCε as the kinase isoforms mediating myotrophin's stimulation of protein synthesis in cardiomyocytes established the upstream signaling entry point for its hypertrophic activity.

    Evidence Isoform-specific antisense knockdown, subcellular fractionation, and pharmacological inhibitors in neonatal and adult rat cardiomyocytes

    PMID:9633917

    Open questions at the time
    • How myotrophin activates PKC isoforms was not determined
    • Downstream effectors beyond PKC were unknown
  3. 2002 High

    Two breakthroughs completed the mechanistic picture in both of MTPN's functional contexts: the PKC–IKKβ–NF-κB pathway was delineated as the signaling cascade through which myotrophin drives hypertrophic gene expression, and separately, V-1/MTPN was identified as a direct stoichiometric inhibitor of capping protein with quantified binding affinity.

    Evidence Dominant-negative IKKβ/IκBα constructs and NF-κB reporter assays in cardiomyocytes (PMID:12486112); tandem affinity purification, SPR kinetics, and in vitro actin polymerization reconstitution (PMID:12488317)

    PMID:12486112 PMID:12488317

    Open questions at the time
    • Whether capping protein sequestration and NF-κB signaling are independent or interconnected functions was unknown
    • In vivo relevance of CP sequestration had not been tested
  4. 2004 High

    Cardiac-specific transgenic overexpression demonstrated that myotrophin is sufficient to drive progressive hypertrophy to heart failure in vivo, establishing it as a bona fide disease driver rather than a correlate.

    Evidence Cardiac-specific myotrophin transgenic mice with longitudinal echocardiography, gene expression profiling, and histomorphology

    PMID:14970239

    Open questions at the time
    • Whether NF-κB was required for the in vivo phenotype was untested
    • The molecular transition point from hypertrophy to failure was undefined
  5. 2008 High

    Genetic epistasis using IκBα triple-mutant mice crossed with myotrophin transgenics proved that continuous NF-κB activation is required for myotrophin-driven cardiac hypertrophy in vivo, closing the loop between the in vitro signaling pathway and the in vivo disease phenotype.

    Evidence Double transgenic mouse model (Myo-Tg × IκBα-3M) with echocardiography and NF-κB gene array

    PMID:18620706

    Open questions at the time
    • Direct NF-κB target genes responsible for the hypertrophic program were not individually validated
    • Whether NF-κB blockade reverses established hypertrophy (not just prevents) was unclear
  6. 2009 High

    shRNA-mediated knockdown of myotrophin reversed established cardiac hypertrophy in transgenic mice, demonstrating that ongoing myotrophin expression is required for disease maintenance and establishing a therapeutic proof of concept.

    Evidence Lentiviral shRNA delivery in vivo and in neonatal rat myocytes with cardiac mass measurement and NF-κB pathway readouts

    PMID:19502558

    Open questions at the time
    • Long-term durability and safety of myotrophin silencing were not assessed
    • Whether partial knockdown is sufficient for regression was not dose-titrated
  7. 2010 Medium

    p53 was identified as a required mediator of the transition from myotrophin-induced hypertrophy to heart failure, distinguishing hypertrophy initiation (NF-κB-dependent) from failure progression (p53-dependent).

    Evidence Double transgenic mice (p53−/− × Myo-Tg) with echocardiography and transcriptomic analysis

    PMID:20202977

    Open questions at the time
    • Biochemical mechanism linking NF-κB signaling to p53 upregulation was not established
    • p53 target genes mediating the failure transition were inferred from pathway analysis, not individually validated
  8. 2016 High

    In vivo validation of MTPN/V-1's capping protein sequestration function in Dictyostelium demonstrated that V-1 exists in molar excess over CP, constitutively sequesters CP in the cytoplasm, regulates pseudopod morphology and Arp2/3 cortical localization, and that this activity is controlled by V-1 phosphorylation.

    Evidence Overexpression, null mutant, and CP-binding-dead mutant analysis in Dictyostelium with F-actin quantification, macropinocytosis/chemotaxis assays, and phosphorylation studies

    PMID:27791032

    Open questions at the time
    • The kinase and phosphatase regulating V-1/MTPN phosphorylation in mammalian cells were not identified
    • Whether CP sequestration contributes to the cardiac hypertrophy phenotype is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A central unresolved question is whether MTPN's two major functions — capping protein sequestration in actin dynamics and PKC–NF-κB signaling in cardiac hypertrophy — are mechanistically linked or represent fully independent activities of the same ankyrin-repeat scaffold.
  • No study has tested whether CP binding and NF-κB activation are mutually exclusive or cooperative
  • The structural determinants on myotrophin distinguishing its CP-binding surface from its hypertrophic signaling function are unmapped
  • Mammalian in vivo confirmation of CP-sequestration phenotypes is lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0098772 molecular function regulator activity 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 GO:0005856 cytoskeleton 2 R-HSA-168256 Immune System 2
Partners
CAPZA1CAPZBIKBKBPRKCAPRKCETP53
Complex memberships
V-1/CP (MTPN–CapZ heterodimer complex)

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Myotrophin (MTPN) activates NF-κB signaling in neonatal rat ventricular cardiomyocytes via the PKC-IKKβ-NF-κB pathway, leading to IκBα phosphorylation and degradation, and subsequent induction of hypertrophic marker genes (ANF, c-myc) and enhanced protein synthesis. Dominant-negative IKKβ or IκBα abrogated these effects. Dominant-negative IKKβ and IκBα expression, NF-κB reporter assay, Western blot, pharmacological inhibition (calphostin C, PDTC), neonatal rat cardiomyocyte culture The Journal of cell biology High 12486112
1998 Myotrophin stimulates protein synthesis in neonatal and adult cardiac myocytes through activation of PKCα and PKCε isoforms. PKCα mediates the response in neonatal myocytes (Ca2+-dependent), while PKCε (Ca2+-independent) operates in both neonatal and adult myocytes. Myotrophin-induced PKC activity is primarily located in the particulate fraction, consistent with membrane translocation. Tyrosine kinase activity is also required, as genistein blocked [3H]leucine incorporation. 32P incorporation kinase assay, subcellular fractionation, antisense oligonucleotides against PKCα and PKCε isoforms, Western blot with PKC isoform-specific antibodies, pharmacological inhibitors (staurosporine, H-7, genistein), neonatal and adult myocyte culture Circulation research High 9633917
1997 NMR structural analysis of myotrophin revealed a secondary structure consisting of seven α-helices connected by turns/loops, with six helices forming three helix-turn-helix motifs corresponding to 2.5 ANK (ankyrin) repeats. A hairpin-like turn (L32–R36) in ANK repeat #1 exhibits slow conformational exchange on the NMR timescale, indicating a dynamically distinct region. The ANK repeat scaffold is consistent with a protein-protein interaction surface. Multidimensional heteronuclear NMR (2D and 3D), 15N- and 15N/13C-uniform labeling, NOE analysis, NH exchange data, coupling constants, chemical shift analysis Protein science : a publication of the Protein Society High 9194197
2002 V-1 (the mouse ortholog of MTPN) binds directly to the α and β subunits of capping protein (CP/CapZ) with a dissociation constant of ~1.2 × 10⁻⁷ M and ~1:1 stoichiometry. V-1 inhibits CP's barbed-end capping activity and thereby suppresses CP-regulated actin polymerization in vitro in a dose-dependent manner. The V-1/CP complex was detected endogenously in cells and murine cerebellar extracts. Tandem affinity purification with mass spectrometry, surface plasmon resonance, in vitro actin polymerization assay, endogenous co-immunoprecipitation from murine cerebellar extracts The Journal of biological chemistry High 12488317
2004 Cardiac-specific overexpression of myotrophin in transgenic mice causes cardiac hypertrophy by 4 weeks of age, progressing to heart failure by 9–12 months. This was associated with increased expression of proto-oncogenes, hypertrophic marker genes, growth factors, and cytokines, and mimicked human cardiomyopathy. Gene expression changes during hypertrophy initiation were distinctly different from those during transition to heart failure, establishing myotrophin as a sufficient in vivo driver of the hypertrophy-to-failure progression. Cardiac-specific transgenic mouse overexpression, echocardiography/functional assessment, gene expression profiling, histomorphology The Journal of biological chemistry High 14970239
2008 Genetic blockade of NF-κB (using IκBα triple mutant mice crossed with myotrophin-overexpressing transgenic mice) significantly attenuated cardiac hypertrophy and improved cardiac function, with inhibition of NF-κB signaling components, hypertrophy marker genes, and inflammatory/macrophage gene expression. This demonstrates that continuous NF-κB activation is required for myotrophin-driven cardiac hypertrophy progression. Double transgenic mouse breeding (Myo-Tg × IκBα-3M), echocardiography, NF-κB-targeted gene array, Western blot, morphometric analysis Journal of molecular biology High 18620706
2009 shRNA-mediated silencing of myotrophin in myotrophin-overexpressing transgenic mice caused significant regression of cardiac mass and myotrophin gene expression, associated with reduction in ANF and NF-κB signaling components. In vitro, lentiviral myotrophin shRNA reduced mRNA and protein levels with concomitant decrease in NF-κB activity in neonatal rat myocytes, establishing a causal relationship between myotrophin expression and NF-κB-dependent hypertrophy. Lentiviral shRNA delivery in vivo and in vitro, cardiac mass measurement, qRT-PCR, Western blot for NF-κB pathway components American journal of physiology. Heart and circulatory physiology High 19502558
2010 p53 expression is upregulated specifically during the transition of myotrophin-induced hypertrophy to heart failure (from 16 weeks onward) in transgenic mice. Crossing myotrophin-overexpressing mice with p53-null mice (p53−/−/myo+/+) significantly reduced cardiac mass and improved cardiac function, demonstrating that p53 is required for myotrophin-driven progression from hypertrophy to heart failure. Key nodal molecules including CDKN1A and caspase-3 were implicated. Double transgenic mouse model (p53−/− × Myo-Tg), immunoblot, real-time RT-PCR, Ingenuity Pathway Analysis, echocardiography Cardiovascular research Medium 20202977
2016 V-1 (MTPN ortholog in Dictyostelium) regulates capping protein (CP) activity in vivo. Overexpression of V-1 reduced pseudopod size and cortical Arp2/3 content, induced filopodia formation, and these effects scaled with expression level and required the CP-binding domain of V-1 (a V-1 mutant unable to bind CP was inactive). V-1-null cells exhibited decreased cellular F-actin content and defects in macropinocytosis and chemotactic aggregation, phenocopying CP overexpression. V-1 was present in molar excess over CP, suggesting constitutive cytoplasmic CP sequestration. Phosphorylation of V-1 was shown to regulate its ability to sequester CP. Overexpression and null mutant analysis in Dictyostelium, fluorescence microscopy, Arp2/3 and F-actin quantification, macropinocytosis and chemotaxis assays, molar ratio determination, CP-binding mutant analysis, phosphorylation studies Proceedings of the National Academy of Sciences of the United States of America High 27791032
2011 Computational modeling of myotrophin's folding thermodynamics and kinetics using the Wako-Saito-Muñoz-Eaton model revealed a weakly three-state equilibrium but two-state-like kinetics consistent with its ankyrin repeat architecture. Two alternative folding pathways (N-terminal and C-terminal) were identified, and the free-energy landscape is 'designed' such that mutations can stabilize intermediates and shift the rate-limiting step. Native-centric WSME model, exact statistical mechanical solution, comparison with experimental folding data, mutational analysis in silico The Journal of chemical physics Low 21341874
2020 Lysyl oxidase (LOX) exerts anti-inflammatory effects in anterior cruciate ligament fibroblasts via the MTPN-mediated NF-κB signaling pathway. Silencing MTPN expression alleviated the anti-inflammatory effect of LOX, suggesting that LOX interacts with MTPN to regulate NF-κB-dependent inflammation. Immunofluorescence showed exogenous LOX localizing to the cell nucleus. RNA sequencing, siRNA knockdown of MTPN, immunofluorescence, protein-protein interaction network analysis, in vitro and in vivo inflammatory models Journal of tissue engineering and regenerative medicine Low 32483895
2021 MTPN is a direct target of miR-885-5p in cholangiocarcinoma (CCA) cells, as confirmed by luciferase reporter assay. Arsenic trioxide (ATO) upregulates miR-885-5p, leading to suppression of MTPN. MTPN knockdown increased CCA cell sensitivity to 5-FU and CDDP, while MTPN overexpression induced drug resistance that could be reversed by ATO, establishing the ATO/miR-885-5p/MTPN axis as a regulator of chemotherapy sensitivity. Luciferase reporter assay (miR-885-5p targeting MTPN 3'UTR), shRNA knockdown, CCK-8 viability assay, Western blot, qRT-PCR, Kaplan-Meier survival analysis Cellular oncology (Dordrecht, Netherlands) Medium 34170484
2000 A myotrophin-like polypeptide from the sponge Suberites domuncula (SUBDOMYOL, 120 aa, sharing high similarity with metazoan myotrophin sequences) stimulates protein synthesis ~5-fold in homologous sponge cells and upregulates collagen gene expression, in a manner analogous to mammalian myotrophin's role in initiating cardiac hypertrophy. Cells incubated with recombinant myotrophin also showed altered morphology (elongated, oval-shaped primmorphs). cDNA cloning, recombinant protein expression, [3H]lysine incorporation assay, RT-PCR for collagen gene expression, morphological analysis FASEB journal : official publication of the Federation of American Societies for Experimental Biology Medium 11023986

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
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
1998 Deletion of the K(V)1.1 potassium channel causes epilepsy in mice. Neuron 482 9581771
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2000 Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. EMBO reports 281 11256614
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2007 From genes to pain: Na v 1.7 and human pain disorders. Trends in neurosciences 218 17950472
2020 Mechanism of adrenergic CaV1.2 stimulation revealed by proximity proteomics. Nature 194 31969708
2020 Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nature cell biology 194 32203420
2003 The DNA sequence of human chromosome 7. Nature 188 12853948
2014 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Molecular cell 173 25544563
2010 A human MAP kinase interactome. Nature methods 165 20936779
2003 Human chromosome 7: DNA sequence and biology. Science (New York, N.Y.) 154 12690205
2019 Defining the Functional Role of NaV1.7 in Human Nociception. Neuron 153 30795902
2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome research 151 11230166
2020 Comparative Application of BioID and TurboID for Protein-Proximity Biotinylation. Cells 146 32344865
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2002 Activation of nuclear factor-kappaB is necessary for myotrophin-induced cardiac hypertrophy. The Journal of cell biology 110 12486112
2008 Functional properties and differential neuromodulation of Na(v)1.6 channels. Molecular and cellular neurosciences 107 18599309
2021 Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice. Science translational medicine 96 33692134
2024 Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis. Nature 90 38172636
2008 Ca(v)1 L-type Ca2+ channel signaling complexes in neurons. Journal of neurochemistry 90 18266933
2020 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. Molecular cell 88 32707033
2021 Paradoxical hyperexcitability from NaV1.2 sodium channel loss in neocortical pyramidal cells. Cell reports 87 34348157
2016 FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1. PLoS biology 82 26752685
2014 Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation. Cell reports 80 24981860
2017 Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones. The Journal of cell biology 78 28515276
2008 Kinomer v. 1.0: a database of systematically classified eukaryotic protein kinases. Nucleic acids research 76 18974176
2019 The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis. Nature communications 74 31586073
2010 Reduced sodium channel Na(v)1.1 levels in BACE1-null mice. The Journal of biological chemistry 72 21190943
2011 Selective silencing of Na(V)1.7 decreases excitability and conduction in vagal sensory neurons. The Journal of physiology 70 22005676
2002 V-1, a protein expressed transiently during murine cerebellar development, regulates actin polymerization via interaction with capping protein. The Journal of biological chemistry 69 12488317
2011 Alternative perspective on intestinal calcium absorption: proposed complementary actions of Ca(v)1.3 and TRPV6. Nutrition reviews 67 21729089
2002 The T cell response to Art v 1, the major mugwort pollen allergen, is dominated by one epitope. Journal of immunology (Baltimore, Md. : 1950) 61 12421987
2018 Voltage and pH sensing by the voltage-gated proton channel, HV1. Journal of the Royal Society, Interface 58 29643227
2017 Visceral and somatic pain modalities reveal NaV 1.7-independent visceral nociceptive pathways. The Journal of physiology 56 28105664
2000 Stimulation of protein (collagen) synthesis in sponge cells by a cardiac myotrophin-related molecule from Suberites domuncula. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 56 11023986
2017 Alternative Splicing of L-type CaV1.2 Calcium Channels: Implications in Cardiovascular Diseases. Genes 53 29186814
2016 Familial gain-of-function Nav1.9 mutation in a painful channelopathy. Journal of neurology, neurosurgery, and psychiatry 53 27503742
2011 Pure haploinsufficiency for Dravet syndrome Na(V)1.1 (SCN1A) sodium channel truncating mutations. Epilepsia 53 22150645
2022 Structural basis for modulation of human NaV1.3 by clinical drug and selective antagonist. Nature communications 52 35277491
2020 Aberrant subchondral osteoblastic metabolism modifies NaV1.8 for osteoarthritis. eLife 50 32441256
2008 Genetics and molecular pathophysiology of Na(v)1.7-related pain syndromes. Advances in genetics 49 19185186
2023 AQP4 Aggravates Cognitive Impairment in Sepsis-Associated Encephalopathy through Inhibiting Nav 1.6-Mediated Astrocyte Autophagy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 48 36922751
2004 Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice. The Journal of biological chemistry 47 14970239
2003 Space-time maps and two-bar interactions of different classes of direction-selective cells in macaque V-1. Journal of neurophysiology 47 12740411
2020 Skeletal muscle CaV1.1 channelopathies. Pflugers Archiv : European journal of physiology 46 32222817
2019 β-adrenergic-mediated dynamic augmentation of sarcolemmal CaV 1.2 clustering and co-operativity in ventricular myocytes. The Journal of physiology 46 30714156
2019 Multiple roles of Bet v 1 ligands in allergen stabilization and modulation of endosomal protease activity. Allergy 46 31230350
2019 Voltage-dependent activation of Rac1 by Nav 1.5 channels promotes cell migration. Journal of cellular physiology 46 31612502
2020 Adrenergic CaV1.2 Activation via Rad Phosphorylation Converges at α1C I-II Loop. Circulation research 44 33086983
1998 Increased protein kinase C activity in myotrophin-induced myocyte growth. Circulation research 44 9633917
2022 Rad regulation of CaV1.2 channels controls cardiac fight-or-flight response. Nature cardiovascular research 42 36424916
2021 Targeting immunodominant Bet v 1 epitopes with monoclonal antibodies prevents the birch allergic response. The Journal of allergy and clinical immunology 42 34126155
2014 Bet v 1--a Trojan horse for small ligands boosting allergic sensitization? Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 42 24979350
2009 The ataxia3 mutation in the N-terminal cytoplasmic domain of sodium channel Na(v)1.6 disrupts intracellular trafficking. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 19261867
2009 Identification of B-cell epitopes of Bet v 1 involved in cross-reactivity with food allergens. Allergy 39 19154550
2019 NaV 1.6 regulates excitability of mechanosensitive sensory neurons. The Journal of physiology 36 31087362
2012 An IgE epitope of Bet v 1 and fagales PR10 proteins as defined by a human monoclonal IgE. Allergy 35 23066955
2009 Activation of neurokinin 3 receptor increases Na(v)1.9 current in enteric neurons. The Journal of physiology 35 19204045
2023 Identification and targeting of a unique NaV1.7 domain driving chronic pain. Proceedings of the National Academy of Sciences of the United States of America 34 37498871
2020 Inhibition of NaV1.8 prevents atrial arrhythmogenesis in human and mice. Basic research in cardiology 34 32078054
2019 Mining the Nav1.7 interactome: Opportunities for chronic pain therapeutics. Biochemical pharmacology 33 30699328
2017 C-terminal phosphorylation of NaV1.5 impairs FGF13-dependent regulation of channel inactivation. The Journal of biological chemistry 30 28882890
2008 Blockade of NF-kappaB using IkappaB alpha dominant-negative mice ameliorates cardiac hypertrophy in myotrophin-overexpressed transgenic mice. Journal of molecular biology 30 18620706
2020 A selective NaV1.1 activator with potential for treatment of Dravet syndrome epilepsy. Biochemical pharmacology 28 32335140
2018 Conotoxin κM-RIIIJ, a tool targeting asymmetric heteromeric Kv1 channels. Proceedings of the National Academy of Sciences of the United States of America 28 30593566
2021 Distinctive Properties and Powerful Neuromodulation of Nav1.6 Sodium Channels Regulates Neuronal Excitability. Cells 27 34202119
2019 TRPV6 and Cav1.3 Mediate Distal Small Intestine Calcium Absorption Before Weaning. Cellular and molecular gastroenterology and hepatology 27 31398491
2019 Absence of Functional Nav1.8 Channels in Non-diseased Atrial and Ventricular Cardiomyocytes. Cardiovascular drugs and therapy 27 31916131
2018 Channeling Vision: CaV1.4-A Critical Link in Retinal Signal Transmission. BioMed research international 27 29854783
2021 Elementary mechanisms of calmodulin regulation of NaV1.5 producing divergent arrhythmogenic phenotypes. Proceedings of the National Academy of Sciences of the United States of America 25 34021086
2020 Sensory neuron-derived NaV1.7 contributes to dorsal horn neuron excitability. Science advances 25 32128393
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
2021 Non-SUMOylated CRMP2 decreases NaV1.7 currents via the endocytic proteins Numb, Nedd4-2 and Eps15. Molecular brain 24 33478555
2021 Mechanisms and Regulation of Cardiac CaV1.2 Trafficking. International journal of molecular sciences 24 34072954
2022 Coordinated conformational changes in the V1 complex during V-ATPase reversible dissociation. Nature structural & molecular biology 23 35469063
2022 Spatiotemporal Control of Vascular CaV1.2 by α1C S1928 Phosphorylation. Circulation research 23 36345826
2018 A New Cardiac Channelopathy: From Clinical Phenotypes to Molecular Mechanisms Associated With Nav1.5 Gating Pores. Frontiers in cardiovascular medicine 23 30356750
2017 The Contribution of L-Type Cav1.3 Channels to Retinal Light Responses. Frontiers in molecular neuroscience 23 29259539
2016 Fine Mapping of Virescent Leaf Gene v-1 in Cucumber (Cucumis sativus L.). International journal of molecular sciences 23 27669214
2024 The V-ATPase/ATG16L1 axis is controlled by the V1H subunit. Molecular cell 22 39089251
2021 The voltage sensor is responsible for ΔpH dependence in Hv1 channels. Proceedings of the National Academy of Sciences of the United States of America 22 33941706
2020 Uncoupling sodium channel dimers restores the phenotype of a pain-linked Nav 1.7 channel mutation. British journal of pharmacology 22 32663327
2018 Small GTPases SAR1A and SAR1B regulate the trafficking of the cardiac sodium channel Nav1.5. Biochimica et biophysica acta. Molecular basis of disease 22 30251687
2016 V-1 regulates capping protein activity in vivo. Proceedings of the National Academy of Sciences of the United States of America 22 27791032
2007 The Ca(v)1.4 calcium channel: more than meets the eye. Channels (Austin, Tex.) 22 19151588
2023 Pathophysiology of Cav1.3 L-type calcium channels in the heart. Frontiers in physiology 21 37025382
2010 Influence of p53 in the transition of myotrophin-induced cardiac hypertrophy to heart failure. Cardiovascular research 21 20202977
1996 Biological and immunological importance of Bet v 1 isoforms. Advances in experimental medicine and biology 21 9095231
2023 Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function. Nature communications 20 37117223
2021 Nav1.7 target modulation and efficacy can be measured in nonhuman primate assays. Science translational medicine 20 34011626
2019 UBC9 regulates cardiac sodium channel Nav1.5 ubiquitination, degradation and sodium current density. Journal of molecular and cellular cardiology 20 30772377
2020 Structural and Functional Characterization of a Nav1.5-Mitochondrial Couplon. Circulation research 19 33342222
2004 Developmental expression of Ca(v)1.3 (alpha1d) calcium channels in the mouse inner ear. Brain research. Developmental brain research 18 15158080
2020 Lysyl oxidase suppresses the inflammatory response in anterior cruciate ligament fibroblasts and promotes tissue regeneration by targeting myotrophin via the nuclear factor-kappa B pathway. Journal of tissue engineering and regenerative medicine 17 32483895
2017 Differential calcium sensitivity in NaV 1.5 mixed syndrome mutants. The Journal of physiology 17 28734073
2017 Nav1.8 neurons are involved in limiting acute phase responses to dietary fat. Molecular metabolism 17 29031710
2021 Regulation of the voltage-dependent sodium channel NaV1.1 by AKT1. Neuropharmacology 16 34375627
2021 PI-QUAL v.1: the first step towards good-quality prostate MRI. European radiology 16 34842957
2020 Elevated EZH2 in ischemic heart disease epigenetically mediates suppression of NaV1.5 expression. Journal of molecular and cellular cardiology 16 33370552
2017 Conformational Flexibility Differentiates Naturally Occurring Bet v 1 Isoforms. International journal of molecular sciences 16 28587205
2011 Analysis of the equilibrium and kinetics of the ankyrin repeat protein myotrophin. The Journal of chemical physics 16 21341874
1997 Nuclear magnetic resonance assignment and secondary structure of an ankyrin-like repeat-bearing protein: myotrophin. Protein science : a publication of the Protein Society 16 9194197
2023 Intranasal CRMP2-Ubc9 inhibitor regulates Na V 1.7 to alleviate trigeminal neuropathic pain. Pain 15 37751532
2022 De novo KCNA6 variants with attenuated KV 1.6 channel deactivation in patients with epilepsy. Epilepsia 15 36318112
2020 The cardiac CaMKII-Nav1.5 relationship: From physiology to pathology. Journal of molecular and cellular cardiology 15 31958466
2021 The ATO/miRNA-885-5p/MTPN axis induces reversal of drug-resistance in cholangiocarcinoma. Cellular oncology (Dordrecht, Netherlands) 14 34170484
2020 Inhibitory Effect of Eslicarbazepine Acetate and S-Licarbazepine on Nav1.5 Channels. Frontiers in pharmacology 14 33123007
2017 The NAv1.7 blocker protoxin II reduces burn injury-induced spinal nociceptive processing. Journal of molecular medicine (Berlin, Germany) 14 29063143
2007 Expression of skeletal muscle Na(V)1.4 Na channel isoform in canine cardiac Purkinje myocytes. Biochemical and biophysical research communications 14 17286959
2021 Loureirin B Exerts its Immunosuppressive Effects by Inhibiting STIM1/Orai1 and KV1.3 Channels. Frontiers in pharmacology 13 34248635
2021 Discovery and characterization of Hv1-type proton channels in reef-building corals. eLife 13 34355697
2020 Functional analysis of three Nav1.6 mutations causing early infantile epileptic encephalopathy. Biochimica et biophysica acta. Molecular basis of disease 13 32916281
2009 Silencing the myotrophin gene by RNA interference leads to the regression of cardiac hypertrophy. American journal of physiology. Heart and circulatory physiology 13 19502558
2023 Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8. Frontiers in molecular neuroscience 12 36860665
2022 Cytosolic peptides encoding CaV1 C-termini downregulate the calcium channel activity-neuritogenesis coupling. Communications biology 12 35589958
2022 Bet v 1-independent sensitization to major allergens in Fagales pollen: Evidence at the T-cell level. Allergy 12 36424884
2020 Pathogenic mutations perturb calmodulin regulation of Nav1.8 channel. Biochemical and biophysical research communications 12 32948286