Affinage

MTPN

Myotrophin · UniProt P58546

Length
118 aa
Mass
12.9 kDa
Annotated
2026-06-10
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MTPN (myotrophin/V-1) is a small cytoplasmic ankyrin-repeat protein with two distinct, well-evidenced activities: it initiates cardiac hypertrophic signaling and it sequesters heterodimeric actin-capping protein to tune actin filament dynamics (PMID:2144530, PMID:11971907, PMID:16895918). Originally purified from hypertensive rat and human cardiomyopathic hearts as a 12 kDa factor that stimulates myocyte protein synthesis, growth, and myofibril organization (PMID:2144530, PMID:8508536), its NMR structure comprises two ankyrin repeats forming helix-turn-helix motifs (PMID:9194197). In the hypertrophic arm, MTPN activates a PKC–IKKβ–NF-κB axis: it stimulates PKCα/PKCε-dependent signaling that drives IκB-α phosphorylation/degradation and NF-κB activation, which is required for MTPN-induced ANF and c-myc expression and protein synthesis (PMID:9633917, PMID:12486112). Through its IκBα/Rel-homologous ankyrin repeats, MTPN binds directly to NF-κB subunits p50, p65, and c-Rel and to κB DNA, translocates to the nucleus during sustained NF-κB activation, and shifts p50-p65 heterodimers toward homodimers to modulate transcriptional output (PMID:8576259, PMID:11971907, PMID:12031792). Cardiac-specific overexpression in mice produces progressive hypertrophy and heart failure, while genetic NF-κB blockade or RNAi silencing of MTPN reverses these phenotypes, establishing MTPN as a causal, NF-κB-dependent driver of cardiac remodeling (PMID:14970239, PMID:18620706, PMID:19502558). In the cytoskeletal arm, MTPN/V-1 binds heterodimeric capping protein 1:1 with nanomolar affinity via loops extending from its ankyrin backbone that engage a basic patch near the CP α/β tentacle, sterically and electrostatically competing with the actin barbed end; it inhibits capping without uncapping pre-capped filaments and allosterically perturbs the CP β-tentacle (PMID:16895918, PMID:20538588, PMID:29847807). In Dictyostelium, V-1 is present in molar excess over CP and tonically suppresses its activity, controlling Arp2/3 cortical content, F-actin levels, macropinocytosis, and chemotaxis in a CP-binding-dependent, phosphorylation-regulated manner (PMID:27791032).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1990 High

    Established that a discrete 12 kDa cardiac factor could itself drive myocyte growth, defining myotrophin as a candidate hypertrophy initiator rather than a generic growth correlate.

    Evidence Purification to homogeneity from hypertensive rat hearts with 3H-leucine incorporation and myofibril morphology bioassay in neonatal cardiomyocytes

    PMID:2144530

    Open questions at the time
    • No receptor or signaling mechanism identified
    • Relevance to human disease not yet addressed
  2. 1993 High

    Extended the hypertrophic activity to human pathology by showing elevated myotrophin in dilated cardiomyopathic hearts, linking the factor to human disease.

    Evidence Protein purification and 3H-leucine bioassay from human hearts with immunoblot comparison of diseased vs normal tissue

    PMID:8508536

    Open questions at the time
    • Correlation, not causation, in human tissue
    • No mechanistic pathway defined
  3. 1996 Medium

    Connected myotrophin to transcriptional control by revealing IκBα-like ankyrin repeats and direct interaction with NF-κB/Rel subunits, suggesting a nuclear signaling role.

    Evidence Sequence analysis plus κB EMSA with p50/p65 supershift and antibody inhibition using recombinant protein

    PMID:8576259

    Open questions at the time
    • EMSA-based binding without in vivo confirmation at this stage
    • Functional consequence on transcription not yet shown
  4. 1997 High

    Provided the structural basis for myotrophin's interactions by determining its two-ankyrin-repeat fold with characteristic helix-turn-helix motifs.

    Evidence Multidimensional heteronuclear NMR on isotopically labeled protein

    PMID:9194197

    Open questions at the time
    • Structure alone does not define binding partners or functional surfaces
    • No bound-complex structure
  5. 1998 High

    Defined the upstream kinase logic of hypertrophy, showing PKCα/PKCε isoform-specific mediation downstream of a tyrosine kinase-coupled pathway.

    Evidence PKC activity assays, isoform-specific antisense and antibodies, inhibitors, and subcellular fractionation in cardiomyocytes

    PMID:9633917

    Open questions at the time
    • Link between PKC activation and transcriptional effectors not yet established
    • Receptor/membrane sensor upstream of PKC unidentified
  6. 1999 Medium

    Cloned human myotrophin and identified it as identical to V-1, unifying two literatures and confirming ubiquitous expression with cardiac functional activity.

    Evidence cDNA cloning, multi-tissue expression profiling, recombinant protein hypertrophy bioassay

    PMID:10329199

    Open questions at the time
    • Tissue-specific functions outside heart not addressed
    • Single-lab cloning characterization
  7. 2002 High

    Integrated the signaling pathway by demonstrating that myotrophin acts through PKC–IKKβ–NF-κB and that NF-κB activation is required for its hypertrophic gene program.

    Evidence NF-κB reporter assays, IκB-α phosphorylation/degradation Westerns, dominant-negative IKKβ and IκB-α, and pharmacological inhibitors in cardiomyocytes

    PMID:12486112

    Open questions at the time
    • How extracellular myotrophin engages this intracellular pathway unresolved
    • Direct vs indirect NF-κB engagement not separated here
  8. 2002 High

    Resolved the nuclear function by showing stimulus-dependent nuclear translocation, in vivo association with p65/c-Rel, and conversion of NF-κB heterodimers into homodimers that alters reporter output.

    Evidence Co-IP (in vivo and in vitro), confocal localization, adenoviral overexpression, luciferase reporter, EMSA

    PMID:11971907

    Open questions at the time
    • Physiological consequence of homodimer shift on endogenous genes not fully mapped
    • Single-lab study
  9. 2002 Medium

    Showed that myotrophin binds κB DNA directly and is itself a mechano- and cytokine-responsive gene, embedding it in stress-responsive transcriptional circuits.

    Evidence EMSA with cardiomyocyte nuclear extracts, confocal localization, cyclic stretch and TNF-α/IL-1β treatment

    PMID:12031792

    Open questions at the time
    • Direct DNA binding by a small ankyrin protein needs structural validation
    • Single-lab EMSA evidence
  10. 2004 High

    Demonstrated sufficiency in vivo: cardiac-specific myotrophin overexpression recapitulates progressive hypertrophy to heart failure with disease-like gene expression.

    Evidence Cardiac-specific transgenic mice with echocardiography, histology, and expression profiling

    PMID:14970239

    Open questions at the time
    • Gain-of-function does not establish requirement of endogenous protein
    • Pathway dependence in vivo not yet tested genetically
  11. 2008 High

    Established genetic epistasis placing NF-κB downstream of myotrophin in vivo, since NF-κB blockade attenuates myotrophin-driven hypertrophy and improves function.

    Evidence Myo-Tg × IκBα triple-mutant double transgenic mice with echocardiography, histology, and NF-κB gene arrays

    PMID:18620706

    Open questions at the time
    • Does not isolate NF-κB from parallel PKC effects
    • Cell-type contributions not dissected
  12. 2009 High

    Confirmed requirement of endogenous myotrophin by RNAi-induced regression of cardiac mass and NF-κB signaling, completing the causal loss-of-function case.

    Evidence Lentiviral shRNA in transgenic mice and neonatal myocytes with qRT-PCR, Western, and cardiac mass measurement

    PMID:19502558

    Open questions at the time
    • Therapeutic durability not assessed
    • Off-target effects of shRNA not fully excluded
  13. 2006 High

    Opened the second functional arm by showing nanomolar, 1:1 binding of V-1 to capping protein at the CP β-tentacle that inhibits barbed-end capping without uncapping.

    Evidence In vitro binding, capping/uncapping assays, mutagenesis of both partners, and molecular dynamics

    PMID:16895918

    Open questions at the time
    • Cellular relevance of CP sequestration not yet shown
    • Regulation of the interaction unknown at this point
  14. 2010 High

    Provided atomic-level mechanism showing V-1 loops bind the CP α-tentacle basic patch in direct competition with the barbed-end electrostatic site, explaining inhibition and the absence of uncapping.

    Evidence NMR chemical shift mapping, intermolecular PRE, and CP site-directed mutagenesis

    PMID:20538588

    Open questions at the time
    • In vivo concentration dependence not addressed here
    • Phosphoregulation not yet defined
  15. 2016 High

    Established physiological function of CP sequestration in cells, showing V-1 tonically suppresses CP to control Arp2/3 networks, F-actin, macropinocytosis, and chemotaxis in a CP-binding-dependent manner.

    Evidence Dictyostelium knockout/overexpression genetics, F-actin and Arp2/3 imaging, motility assays, WT vs CP-binding-mutant rescue

    PMID:27791032

    Open questions at the time
    • Direct demonstration of equivalent role in mammalian cells absent from corpus
    • Identity of the regulatory kinase and phosphosites unresolved
  16. 2018 High

    Revealed an allosteric dimension to CP regulation, showing V-1 and CARMIL bind distinct sites yet both reshape the CP β-tentacle, coupling modulator binding to actin-binding surfaces.

    Evidence Hydrogen-deuterium exchange mass spectrometry on CP complexes

    PMID:29847807

    Open questions at the time
    • Functional consequence of allosteric coupling in cells not measured
    • Single-lab biophysical study
  17. 2020 Low

    Implicated MTPN in inflammatory signaling beyond the heart, with LOX-mediated suppression of TNF-α responses dependent in part on MTPN.

    Evidence RNA-seq, interaction network analysis, MTPN siRNA, immunofluorescence in ACL fibroblasts and an animal model

    PMID:32483895

    Open questions at the time
    • LOX–MTPN interaction not established by binding or co-IP
    • MTPN role inferred from knockdown within a larger study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MTPN's two activities—NF-κB modulation and CP sequestration—are coordinated within the same cell, and what kinase and signals control the phosphoregulation of CP binding, remains unresolved.
  • No identified kinase or phosphosite for CP-binding regulation
  • No integrated model linking transcriptional and cytoskeletal functions
  • Mammalian-cell role of CP sequestration not directly demonstrated in corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2
Partners
CAPZA1CAPZBNFKB1RELRELA

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Myotrophin was purified to apparent homogeneity from spontaneously hypertensive rat hearts as a novel 12 kDa protein that stimulates protein synthesis and myocardial cell growth in isolated neonatal cardiac myocytes, causing increased surface area and organized myofibril formation in a dose-dependent manner. Protein purification, bioassay (3H-leucine incorporation into myocyte protein), amino acid sequencing, morphological assessment of myocyte surface area and myofibril organization The Journal of biological chemistry High 2144530
1993 Human myotrophin purified from dilated cardiomyopathic hearts is a single 12 kDa polypeptide that stimulates adult myocardial protein synthesis and cell growth, with significantly elevated levels in dilated cardiomyopathic versus normal human hearts. Protein purification (reverse-phase HPLC, SDS-PAGE), 3H-leucine incorporation bioassay, Western blot, immunoblot with rat myotrophin antibody Circulation research High 8508536
1996 Myotrophin protein contains ankyrin repeats with high homology to IκBα/rel ankyrin repeats, and recombinant myotrophin interacts directly with NF-κB/rel proteins (p50 and p65) as demonstrated by formation of ternary protein-DNA complexes in kappa B gel shift assays; myotrophin-specific antibodies inhibited these complexes. Sequence analysis, kappa B gel shift assay (EMSA), supershift assay with rel-specific p50 and p65 antibodies, antibody inhibition The Journal of biological chemistry Medium 8576259
1997 NMR analysis revealed that myotrophin consists of seven helices forming three helix-turn-helix motifs, with two full ankyrin repeats characterized by multiple turns followed by helix-turn-helix motifs; a hairpin-like turn in ANK repeat #1 (L32-R36) shows slow conformational averaging distinct from ANK repeat #2. Multidimensional heteronuclear NMR (2D and 3D) on uniformly 15N-labeled and 15N/13C-labeled protein; NOE analysis, NH exchange, coupling constants, chemical shift analysis Protein science : a publication of the Protein Society High 9194197
1998 Myotrophin stimulates PKC activity and protein synthesis in neonatal cardiac myocytes through a tyrosine kinase-coupled pathway; PKCα and PKCε isoforms mediate myotrophin-induced neonatal myocyte growth, whereas only PKCε mediates adult myocyte hypertrophy. Myotrophin-induced PKC activity is located predominantly in the particulate (membrane) fraction. PKC activity assay (32P incorporation into histone and PKCε substrate peptide), 3H-leucine incorporation, pharmacological inhibitors (staurosporine, H-7, calphostin C, genistein), Western blot with isoform-specific antibodies, antisense oligonucleotides, subcellular fractionation Circulation research High 9633917
1999 Human myotrophin/V-1 cDNA was cloned and characterized; the protein is identical to previously described V-1 proteins, is ubiquitously expressed with high expression in heart, and recombinant human myotrophin produces cardiomyocyte hypertrophy in vitro. cDNA cloning, Northern blot, Southern blot, dot blot (50 tissues), recombinant protein expression and functional bioassay Journal of molecular and cellular cardiology Medium 10329199
2002 Myotrophin/V-1 is predominantly cytoplasmic but translocates to the nucleus during sustained NF-κB activation. It interacts physically with p65 and c-Rel proteins in vivo during NF-κB activation (co-IP), and in vitro promotes conversion of p50-p65 heterodimers into p50-p50 and p65-p65 homodimers. Adenoviral overexpression of myotrophin/V-1 increased p50-p50 homodimers and reduced κB-luciferase reporter activity. Co-immunoprecipitation (in vivo and in vitro), confocal microscopy (subcellular localization), 3D structural alignment, adenoviral overexpression, luciferase reporter assay, EMSA The Journal of biological chemistry High 11971907
2002 NF-κB activation is required for myotrophin-induced cardiac hypertrophy: myotrophin treatment stimulates NF-κB nuclear translocation and transcriptional activity via IκB-α phosphorylation and degradation through a PKC-IKKβ-NF-κB pathway. Dominant-negative IKKβ or IκB-α blocked myotrophin-induced ANF and c-myc expression and protein synthesis. NF-κB reporter assay, Western blot for IκB-α phosphorylation/degradation, dominant-negative constructs (IKKβ, IκB-α), pharmacological inhibitors (PDTC, calphostin C), 3H-leucine incorporation The Journal of cell biology High 12486112
2002 Myotrophin binds directly to κB DNA, as shown by gel mobility shift assay with nuclear extracts from neonatal and adult cardiomyocytes. Under cyclic stretch, myotrophin levels increase in the nucleus. Myotrophin gene expression is upregulated by cyclic stretch, TNF-α, IL-1β, and high pressure in beating hearts. Gel mobility shift assay (EMSA), confocal microscopy (subcellular localization), recombinant protein, cyclic stretch model, pharmacological treatment Biochimica et biophysica acta Medium 12031792
2004 Cardiac-specific overexpression of myotrophin in transgenic mice causes progressive cardiac hypertrophy by 4 weeks of age, progressing to heart failure by 9–12 months, with increased expression of proto-oncogenes, hypertrophy marker genes, growth factors, and cytokines mimicking human cardiomyopathy. Transgenic mouse model (cardiac-specific overexpression), echocardiography, histology, gene expression profiling The Journal of biological chemistry High 14970239
2006 Myotrophin/V-1 binds directly to heterodimeric actin-capping protein (CP) in a 1:1 molar ratio with Kd of 10–50 nM. V-1 binding inhibits CP's ability to cap actin filament barbed ends. The CP β-subunit C-terminal 'tentacle' is the primary binding site on CP for V-1. Two loops of V-1 extending from its ankyrin repeat backbone are necessary for V-1 to bind CP. V-1 appears unable to bind CP already on the barbed end and has no uncapping activity. In vitro binding assays, actin barbed-end capping assays, uncapping assays, site-directed mutagenesis (V-1 loops and CP subunit regions), computational modeling and molecular dynamics simulations The Journal of biological chemistry High 16895918
2008 Genetic blockade of NF-κB (via IκBα triple mutant mice crossed with myotrophin-overexpressing transgenic mice) attenuates myotrophin-induced cardiac hypertrophy and improves cardiac function, demonstrating that continuous NF-κB blockade is effective against myotrophin-driven cardiac remodeling. Double transgenic mice (Myo-Tg × IκBα triple mutant), echocardiography, histology, NF-κB gene array profiling, apoptosis markers Journal of molecular biology High 18620706
2009 RNA interference (shRNA lentiviral delivery) silencing of myotrophin in myotrophin-overexpressing transgenic mice causes regression of cardiac mass and reduction in NF-κB signaling and ANF expression, establishing a causal role for myotrophin in NF-κB-dependent cardiac hypertrophy. Lentiviral shRNA delivery in vivo and in vitro (neonatal rat myocytes), qRT-PCR, Western blot, cardiac mass measurement American journal of physiology. Heart and circulatory physiology High 19502558
2010 NMR chemical shift mapping and intermolecular paramagnetic relaxation enhancement experiments revealed that the ankyrin loops of V-1 bind to the basic patch near the joint of the α tentacle of CP. Site-directed mutagenesis of CP confirmed that V-1 and the electrostatic barbed-end binding site on CP compete for this same basic patch, explaining how V-1 inactivates barbed end capping and why V-1 cannot uncap CP-capped actin filaments. NMR (chemical shift mapping, intermolecular PRE experiments), site-directed mutagenesis of CP The Journal of biological chemistry High 20538588
2011 Porcine MTPN protein is localized to the cytoplasm of Pig Kidney Epithelial (PK15) cells as determined by transient transfection, and is widely expressed across tissues with high levels in spleen, liver, and uterus; expression peaks at embryonic day 65 and is down-regulated postnatally during skeletal muscle development. Transient transfection with subcellular localization imaging, RT-PCR, qRT-PCR, cDNA cloning, genomic structure analysis Molecular biology reports Medium 21667249
2016 V-1/Myotrophin regulates capping protein (CP) activity in vivo in Dictyostelium: overexpression of V-1 reduced pseudopod size and cortical Arp2/3 content and induced filopodia in a CP-binding-dependent manner (a V-1 mutant unable to bind CP had no effect). V-1-null cells showed decreased cellular F-actin content and defects in macropinocytosis and chemotactic aggregation rescued by wild-type but not CP-binding-deficient V-1. V-1 is present in molar excess over CP suggesting it tonically suppresses CP activity in the cytoplasm. Evidence that V-1's CP-sequestering activity is regulated by phosphorylation was also obtained. Dictyostelium overexpression and knockout genetics, fluorescence microscopy (Arp2/3 and F-actin quantification), macropinocytosis assay, chemotaxis assay, rescue experiments with WT and mutant V-1 Proceedings of the National Academy of Sciences of the United States of America High 27791032
2018 V-1 and CARMIL bind to distinct sites on capping protein and induce allosteric conformational changes in CP detected by hydrogen-deuterium exchange mass spectrometry. Both V-1 and CARMIL affect the conformation of CP's ββ subunit tentacle (a second actin-binding site distal from their respective binding sites), revealing allosteric coupling between CP modulator and actin binding sites. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) Cell reports High 29847807
2020 Lysyl oxidase (LOX) suppresses TNF-α-induced inflammatory responses in ACL fibroblasts partly via MTPN: silencing MTPN expression alleviated the anti-inflammatory effect of LOX, suggesting LOX interacts with MTPN to regulate inflammation through the NF-κB signaling pathway. RNA sequencing, protein-protein interaction network analysis, siRNA knockdown of MTPN, immunofluorescence, in vivo animal model Journal of tissue engineering and regenerative medicine Low 32483895

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Deletion of the K(V)1.1 potassium channel causes epilepsy in mice. Neuron 482 9581771
2007 From genes to pain: Na v 1.7 and human pain disorders. Trends in neurosciences 220 17950472
2020 Mechanism of adrenergic CaV1.2 stimulation revealed by proximity proteomics. Nature 202 31969708
2009 Cardiac sodium channel Na(v)1.5 and interacting proteins: Physiology and pathophysiology. Journal of molecular and cellular cardiology 202 19744495
2000 Expression of silicatein and collagen genes in the marine sponge Suberites domuncula is controlled by silicate and myotrophin. European journal of biochemistry 187 10903523
2002 Activation of nuclear factor-kappaB is necessary for myotrophin-induced cardiac hypertrophy. The Journal of cell biology 111 12486112
2018 Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death. Proceedings of the National Academy of Sciences of the United States of America 108 30076230
2024 Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis. Nature 94 38172636
2018 Cardiac Kir2.1 and NaV1.5 Channels Traffic Together to the Sarcolemma to Control Excitability. Circulation research 92 29514831
2008 Ca(v)1 L-type Ca2+ channel signaling complexes in neurons. Journal of neurochemistry 90 18266933
2021 Paradoxical hyperexcitability from NaV1.2 sodium channel loss in neocortical pyramidal cells. Cell reports 89 34348157
2010 Ca(v)1.3 and BK channels for timing and regulating cell firing. Molecular neurobiology 89 21088933
1990 Myotrophin: purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth. The Journal of biological chemistry 78 2144530
2010 Reduced sodium channel Na(v)1.1 levels in BACE1-null mice. The Journal of biological chemistry 72 21190943
2011 Alternative perspective on intestinal calcium absorption: proposed complementary actions of Ca(v)1.3 and TRPV6. Nutrition reviews 68 21729089
2019 SCN1A/NaV 1.1 channelopathies: Mechanisms in expression systems, animal models, and human iPSC models. Epilepsia 60 31904127
2018 Voltage and pH sensing by the voltage-gated proton channel, HV1. Journal of the Royal Society, Interface 58 29643227
2019 Cold sensing by NaV1.8-positive and NaV1.8-negative sensory neurons. Proceedings of the National Academy of Sciences of the United States of America 56 30755524
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
2006 Binding of myotrophin/V-1 to actin-capping protein: implications for how capping protein binds to the filament barbed end. The Journal of biological chemistry 55 16895918
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
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 52 32441256
2008 Genetics and molecular pathophysiology of Na(v)1.7-related pain syndromes. Advances in genetics 49 19185186
2020 Skeletal muscle CaV1.1 channelopathies. Pflugers Archiv : European journal of physiology 48 32222817
2019 Voltage-dependent activation of Rac1 by Nav 1.5 channels promotes cell migration. Journal of cellular physiology 47 31612502
2009 Protein kinase C isoforms differentially phosphorylate Ca(v)1.2 alpha(1c). Biochemistry 47 19527072
2004 Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice. The Journal of biological chemistry 47 14970239
2022 Rad regulation of CaV1.2 channels controls cardiac fight-or-flight response. Nature cardiovascular research 46 36424916
2021 Targeting immunodominant Bet v 1 epitopes with monoclonal antibodies prevents the birch allergic response. The Journal of allergy and clinical immunology 45 34126155
1998 Increased protein kinase C activity in myotrophin-induced myocyte growth. Circulation research 45 9633917
2020 Adrenergic CaV1.2 Activation via Rad Phosphorylation Converges at α1C I-II Loop. Circulation research 44 33086983
2002 Myotrophin/V-1, a protein up-regulated in the failing human heart and in postnatal cerebellum, converts NFkappa B p50-p65 heterodimers to p50-p50 and p65-p65 homodimers. The Journal of biological chemistry 43 11971907
2017 Sodium channel NaV1.3 is important for enterochromaffin cell excitability and serotonin release. Scientific reports 39 29142310
1996 Cardiac myotrophin exhibits rel/NF-kappa B interacting activity in vitro. The Journal of biological chemistry 39 8576259
2019 NaV 1.6 regulates excitability of mechanosensitive sensory neurons. The Journal of physiology 38 31087362
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 37 37498871
1993 Myotrophin in human cardiomyopathic heart. Circulation research 37 8508536
2010 Structural basis for capping protein sequestration by myotrophin (V-1). The Journal of biological chemistry 36 20538588
2020 Inhibition of NaV1.8 prevents atrial arrhythmogenesis in human and mice. Basic research in cardiology 35 32078054
2018 Regulation of Blood Pressure by Targeting CaV1.2-Galectin-1 Protein Interaction. Circulation 35 29650545
2022 NaV1.1 is essential for proprioceptive signaling and motor behaviors. eLife 30 36278870
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
2021 Distinctive Properties and Powerful Neuromodulation of Nav1.6 Sodium Channels Regulates Neuronal Excitability. Cells 29 34202119
2020 A selective NaV1.1 activator with potential for treatment of Dravet syndrome epilepsy. Biochemical pharmacology 29 32335140
2019 TRPV6 and Cav1.3 Mediate Distal Small Intestine Calcium Absorption Before Weaning. Cellular and molecular gastroenterology and hepatology 28 31398491
2019 Absence of Functional Nav1.8 Channels in Non-diseased Atrial and Ventricular Cardiomyocytes. Cardiovascular drugs and therapy 28 31916131
2021 Mechanisms and Regulation of Cardiac CaV1.2 Trafficking. International journal of molecular sciences 27 34072954
2020 Sensory neuron-derived NaV1.7 contributes to dorsal horn neuron excitability. Science advances 27 32128393
2018 KV4.3 Expression Modulates NaV1.5 Sodium Current. Frontiers in physiology 27 29593552
2018 Channeling Vision: CaV1.4-A Critical Link in Retinal Signal Transmission. BioMed research international 27 29854783
2020 Multiple Sequence Variants in STAC3 Affect Interactions with CaV1.1 and Excitation-Contraction Coupling. Structure (London, England : 1993) 26 32492370
2024 The V-ATPase/ATG16L1 axis is controlled by the V1H subunit. Molecular cell 25 39089251
2022 Spatiotemporal Control of Vascular CaV1.2 by α1C S1928 Phosphorylation. Circulation research 25 36345826
2023 Pathophysiology of Cav1.3 L-type calcium channels in the heart. Frontiers in physiology 24 37025382
2023 Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function. Nature communications 24 37117223
2022 Coordinated conformational changes in the V1 complex during V-ATPase reversible dissociation. Nature structural & molecular biology 24 35469063
2021 Non-SUMOylated CRMP2 decreases NaV1.7 currents via the endocytic proteins Numb, Nedd4-2 and Eps15. Molecular brain 24 33478555
2022 NaV1.1 haploinsufficiency impairs glutamatergic and GABAergic neuron function in the thalamus. Neurobiology of disease 23 35219855
2003 Myotrophin in human heart failure. Journal of the American College of Cardiology 23 12932609
2018 Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange. Cell reports 22 29847807
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
1999 cDNA sequence and characterization of the gene that encodes human myotrophin/V-1 protein, a mediator of cardiac hypertrophy. Journal of molecular and cellular cardiology 22 10329199
2021 Nav1.7 target modulation and efficacy can be measured in nonhuman primate assays. Science translational medicine 21 34011626
2019 UBC9 regulates cardiac sodium channel Nav1.5 ubiquitination, degradation and sodium current density. Journal of molecular and cellular cardiology 21 30772377
1996 Biological and immunological importance of Bet v 1 isoforms. Advances in experimental medicine and biology 21 9095231
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 20 32483895
2020 Structural and Functional Characterization of a Nav1.5-Mitochondrial Couplon. Circulation research 20 33342222
2002 Myotrophin-kappaB DNA interaction in the initiation process of cardiac hypertrophy. Biochimica et biophysica acta 18 12031792
1995 Quantification of myotrophin from spontaneously hypertensive and normal rat hearts. Circulation research 18 7758156
2021 Regulation of the voltage-dependent sodium channel NaV1.1 by AKT1. Neuropharmacology 17 34375627
2017 Nav1.8 neurons are involved in limiting acute phase responses to dietary fat. Molecular metabolism 17 29031710
2023 Nav1.7 gain-of-function mutation I228M triggers age-dependent nociceptive insensitivity and C-LTMR dysregulation. Experimental neurology 16 37003485
2021 The ATO/miRNA-885-5p/MTPN axis induces reversal of drug-resistance in cholangiocarcinoma. Cellular oncology (Dordrecht, Netherlands) 16 34170484
2021 Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits. Scientific reports 16 34312446
2021 PI-QUAL v.1: the first step towards good-quality prostate MRI. European radiology 16 34842957
2020 The cardiac CaMKII-Nav1.5 relationship: From physiology to pathology. Journal of molecular and cellular cardiology 16 31958466
2020 Elevated EZH2 in ischemic heart disease epigenetically mediates suppression of NaV1.5 expression. Journal of molecular and cellular cardiology 16 33370552
2017 9-cis Retinoic acid modulates myotrophin expression and its miR in physiological and pathophysiological cell models. Experimental cell research 16 28300567
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
2020 Inhibitory Effect of Eslicarbazepine Acetate and S-Licarbazepine on Nav1.5 Channels. Frontiers in pharmacology 14 33123007
2021 Discovery and characterization of Hv1-type proton channels in reef-building corals. eLife 13 34355697
2018 Mutation in Nav 1.7 causes high olfactory sensitivity. European journal of pain (London, England) 13 29934995
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
2023 Calmodulin mutations affecting Gly114 impair binding to the NaV1.5 IQ-domain. Frontiers in pharmacology 12 37663247
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
2021 Voltage sensor movements of CaV1.1 during an action potential in skeletal muscle fibers. Proceedings of the National Academy of Sciences of the United States of America 12 34583989
2020 Pathogenic mutations perturb calmodulin regulation of Nav1.8 channel. Biochemical and biophysical research communications 12 32948286
2019 Centipede KCNQ Inhibitor SsTx Also Targets KV1.3. Toxins 12 30717088
2017 A functional coupling between CRMP1 and Nav1.7 for retrograde propagation of Semaphorin3A signaling. Journal of cell science 12 28254884
2001 S-myotrophin promotes the hypertrophy of myotube as insulin-like growth factor-I does. The international journal of biochemistry & cell biology 12 11404186
2022 Evaluation of Nav1.8 as a therapeutic target for Pitt Hopkins Syndrome. Molecular psychiatry 11 36224259
2021 Function of cone and cone-related pathways in CaV1.4 IT mice. Scientific reports 11 33526839
2011 Molecular characterization, expression patterns and subcellular localization of Myotrophin (MTPN) gene in porcine skeletal muscle. Molecular biology reports 11 21667249

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