Affinage

TPM1

Tropomyosin alpha-1 chain · UniProt P09493

Length
284 aa
Mass
32.7 kDa
Annotated
2026-04-28
81 papers in source corpus 35 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TPM1 encodes α-tropomyosin, an actin-binding coiled-coil protein that stabilizes actin filaments and regulates actomyosin interactions across muscle and non-muscle cell types. In striated muscle, TPM1 controls thin filament activation by occupying Ca²⁺-dependent azimuthal positions on actin: hypertrophic cardiomyopathy (HCM) mutations (e.g., D175N, E180G, E192K, S215L) destabilize the blocked state and shift tropomyosin toward the open position, increasing Ca²⁺ sensitivity and crossbridge activity, while dilated cardiomyopathy (DCM) mutations (e.g., E40K, E54K, M8R, K30E) favor the blocked/inactive state and reduce Ca²⁺ sensitivity, with pharmacological rescue by the myosin inhibitor mavacamten confirming excess crossbridge activity as the HCM pathogenic mechanism (PMID:25548289, PMID:34319370, PMID:39436707, PMID:39282088). In non-muscle cells, alternatively spliced TPM1 isoforms exhibit distinct actin affinities and thermal stabilities, stabilize specific actin filament populations by inhibiting cofilin-1-mediated severing, and are required for polarized vesicle transport, platelet adhesion, and endothelial junction integrity (PMID:1629236, PMID:34067970, PMID:41067737, PMID:34604206). TPM1 expression is subject to multilayered regulation including N-terminal acetylation by the NatB/Mdm20 complex required for F-actin binding, alternative splicing controlled by MBNL1/PTB and SRSF6, miRNA-mediated translational repression (miR-21, miR-183), and EZH2-dependent H3K27me3 promoter silencing in cancer contexts (PMID:12808144, PMID:23511971, PMID:17363372, PMID:33499872).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1992 High

    Establishing that tropomyosin is not merely a structural actin-binding protein but actively required for directed vesicular transport resolved how actin cables function in polarized secretion.

    Evidence Genetic disruption of yeast TPM1, epistasis with sec and myo2 mutations, EM and secretion assays in S. cerevisiae

    PMID:1629236

    Open questions at the time
    • Mechanism by which tropomyosin-decorated cables facilitate vesicle movement not defined
    • No direct visualization of vesicle transport along cables
  2. 1995 High

    Demonstrating that Tpm1p and Tpm2p span different numbers of actin monomers and perform non-redundant functions established the principle of isoform-specific tropomyosin regulation of actin filaments.

    Evidence Biochemical purification, F-actin binding competition assays, and genetic complementation in yeast

    PMID:7844152

    Open questions at the time
    • Structural basis for different actin-spanning lengths not resolved
    • Which downstream effectors are differentially regulated by Tpm1p vs Tpm2p unknown
  3. 2000 Medium

    Identification of suppressor mutations in TPM1 and ACT1 that rescue mdm20Δ defects revealed that tropomyosin-actin interaction strength is the critical parameter for cable stability, foreshadowing the role of N-terminal acetylation.

    Evidence Suppressor screen and genetic epistasis analysis in yeast

    PMID:11014803

    Open questions at the time
    • Biochemical mechanism of suppression not demonstrated in vitro
    • Whether suppressor alleles alter actin-tropomyosin interface directly unknown
  4. 2003 High

    Showing that NatB/Mdm20-mediated N-terminal acetylation is required for Tpm1p to bind F-actin established a direct post-translational prerequisite for tropomyosin function and actin cable assembly.

    Evidence In vivo acetylation assays, F-actin co-sedimentation, genetic epistasis with NatB components in yeast

    PMID:12808144

    Open questions at the time
    • Structural mechanism by which acetylation promotes head-to-tail polymerization and actin binding not resolved
    • Whether this requirement is conserved for mammalian TPM1 not directly tested
  5. 2007 High

    Discovery that miR-21 directly targets the TPM1 3′-UTR to suppress protein expression established TPM1 as a post-transcriptionally regulated tumor suppressor in breast cancer.

    Evidence Luciferase reporter assay with WT and deletion 3′-UTR constructs, Western blot, proteomics in MCF-7 cells

    PMID:17363372

    Open questions at the time
    • Whether miR-21-mediated TPM1 suppression is sufficient for transformation in vivo not tested
    • Contribution of individual TPM1 isoforms to tumor suppression unclear
  6. 2008 High

    Identification of hnRNP H/F binding to a G-rich silencer in a TPM1 nonsense exon, with systematic mutagenesis validating enhancer/silencer predictions, provided a detailed map of cis-elements governing TPM1 alternative splicing.

    Evidence Mutagenesis of 13 predicted regulatory elements and RNA binding assays for hnRNP H/F in rat Tpm1 minigene

    PMID:19037011

    Open questions at the time
    • Whether these regulatory elements function identically in human TPM1 not confirmed
    • Combinatorial effects of multiple RNA-binding proteins on this exon not fully explored
  7. 2011 Medium

    Polarized fluorimetry of HCM (D175N, E180G) and DCM (E40K) mutations demonstrated that cardiomyopathy mutations shift tropomyosin's azimuthal position on actin in opposing directions, establishing the structural basis for the hypercontractility/hypocontractility dichotomy.

    Evidence Fluorescence polarization of labeled tropomyosin, actin, and S1 in ghost muscle fibers during ATPase cycle

    PMID:21376702 PMID:21741356 PMID:22155441

    Open questions at the time
    • Ghost fiber system uses exchanged tropomyosin without troponin reconstitution in all cases
    • Single-lab observations awaiting independent replication
  8. 2013 High

    Demonstrating that MBNL1 and PTB cooperatively repress TPM1 exon 3 splicing via a conformational change-dependent protein–protein interaction revealed how combinatorial splicing factor control generates tissue-specific tropomyosin isoforms.

    Evidence RNA binding assays, domain deletion analysis, single-molecule PTB binding cooperativity analysis on rat Tpm1 pre-mRNA

    PMID:23511971

    Open questions at the time
    • In vivo validation of MBNL1-PTB cooperation at endogenous Tpm1 locus not shown
    • Whether MBNL1 loss (as in myotonic dystrophy) affects TPM1 splicing in human muscle not directly tested
  9. 2014 High

    Systematic analysis of seven HCM/DCM mutations using reconstituted human β-cardiac myosin ATPase assays confirmed that HCM mutations uniformly increase and DCM mutations decrease Ca²⁺ sensitivity, unifying the mechanistic framework across the mutation spectrum.

    Evidence Ca²⁺-dependent ATPase activity, TnC conformational probes, thermal stability assays with recombinant mutant tropomyosins

    PMID:25548289

    Open questions at the time
    • Cellular-level consequences of each mutation not assessed in this study
    • Contributions of altered protein stability vs. altered thin filament regulation not fully disentangled
  10. 2017 Medium

    Discovery that a natural antisense lncRNA (TPM1-AS) inhibits RBM4-mediated inclusion of TPM1 exon 2a added a non-coding RNA layer to isoform-specific TPM1 regulation with functional consequences for cancer cell migration.

    Evidence RNA immunoprecipitation, alternative splicing analysis, knockdown/overexpression in esophageal cancer cells

    PMID:28754317

    Open questions at the time
    • Structural basis of TPM1-AS/RBM4 interaction not defined
    • Whether TPM1-AS operates in non-cancer contexts unknown
  11. 2021 High

    Pharmacological rescue of TPM1 E192K-driven hypertrophy and diastolic dysfunction by mavacamten in patient iPSC-derived engineered heart tissues provided causal proof that excess crossbridge activity is the pathogenic mechanism in TPM1-linked HCM, validating a therapeutic strategy.

    Evidence Patient iPSC-derived engineered heart tissues, in vitro motility, molecular dynamics, mavacamten treatment

    PMID:34319370

    Open questions at the time
    • Long-term in vivo efficacy of mavacamten for TPM1 mutations not tested
    • Whether all HCM-causing TPM1 mutations respond equally to mavacamten unknown
  12. 2021 Medium

    Multiple independent studies converged on EZH2-mediated H3K27me3 silencing of the TPM1 promoter (recruited by lncRNAs LINC01116 and ELFN1-AS1) as an epigenetic mechanism of TPM1 suppression in colorectal cancer, generalizing TPM1 as a transcriptionally silenced tumor suppressor.

    Evidence ChIP for EZH2 and H3K27me3 at TPM1 promoter, RNA pull-down, RIP, luciferase reporter assays

    PMID:33499872 PMID:35857351

    Open questions at the time
    • Whether EZH2-mediated silencing occurs across other cancer types not established
    • Functional contribution of individual lncRNAs vs redundancy not resolved
  13. 2021 Medium

    CRISPR-based activation of endogenous TPM1 in coronary artery endothelial cells showed that TPM1 stabilizes VE-cadherin-based cell junctions and suppresses TNFα-induced inflammation, linking cytoskeletal regulation to endothelial barrier function.

    Evidence CRISPRa, immunofluorescence for F-actin and junctional proteins, migration assays in primary human endothelial cells

    PMID:34604206

    Open questions at the time
    • Which TPM1 isoform(s) mediate endothelial effects not defined
    • In vivo vascular permeability data not provided
  14. 2021 Medium

    Characterization of five cytoplasmic TPM1 isoforms revealed that alternative exon usage at N-terminal, internal, and C-terminal positions determines distinct thermal stabilities and F-actin affinities, providing a biochemical code for isoform-specific actin filament regulation.

    Evidence Recombinant protein purification, thermal stability assays, F-actin co-sedimentation for Tpm1.5, 1.6, 1.7, 1.12, Tpm4.2

    PMID:34067970

    Open questions at the time
    • Cellular functions uniquely assigned to each isoform not determined
    • Structural basis for affinity differences not resolved
  15. 2022 High

    Demonstration that a lethal TPM1 mutation disrupting myofibril assembly can be rescued by a variant in TLN2 established the principle of genetic suppression between actin-binding proteins in human cardiomyopathy, explaining incomplete penetrance.

    Evidence Patient iPSC-derived cardiomyocytes, CRISPR knock-in of both TPM1 and TLN2 variants in mice with embryonic lethality rescue

    PMID:35243414

    Open questions at the time
    • Molecular mechanism of TLN2-mediated suppression not defined
    • Frequency of TLN2 modifier effects in cardiomyopathy cohorts unknown
  16. 2022 Medium

    Identification of systemic TPM1 as a circulating pro-aging factor that induces neuroinflammation via PKA/FABP5/NF-κB signaling expanded TPM1's role beyond cytoskeletal regulation to intercellular signaling.

    Evidence Heterochronic parabiosis, plasma transfer, recombinant TPM1 administration, neutralizing antibody depletion in mice

    PMID:35148456

    Open questions at the time
    • Source cells releasing TPM1 into plasma not identified
    • Whether circulating TPM1 retains actin-binding capacity or acts through a receptor unknown
  17. 2024 High

    Integrated computational-experimental analyses of HCM E62Q and DCM E54K mutations revealed that even mutations in the same region of tropomyosin can operate through fundamentally different molecular mechanisms — altered molecular stiffness vs. long-range allosteric modulation of troponin I binding — refining the hypercontractility/hypocontractility framework.

    Evidence Computational simulations, stem cell-derived cardiomyocytes, pharmacological rescue with myosin modulators, engineered heart tissues

    PMID:39436707

    Open questions at the time
    • Whether allosteric mechanism of E54K generalizes to other DCM mutations not tested
    • Structural validation of altered TnI-tropomyosin/actin binding kinetics awaits cryo-EM
  18. 2025 Medium

    Demonstration that non-muscle TPM1 isoforms inhibit cofilin-1 binding and prevent cofilin-1-induced F-actin severing in an isoform-specific manner provided a direct mechanism for how tropomyosin stabilizes distinct actin populations in non-muscle cells.

    Evidence Co-sedimentation, viscometry, rhodamine-phalloidin displacement assays with multiple recombinant TPM1 isoforms

    PMID:41067737

    Open questions at the time
    • Cellular validation that specific isoforms protect specific actin populations from cofilin in vivo not shown
    • Whether TPM1 isoforms also regulate other actin-severing/depolymerizing factors not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of TPM1 isoform-specific actin decoration and functional specialization in non-muscle cells; whether circulating TPM1 acts through a dedicated receptor; and how the full spectrum of splicing regulators (MBNL1, PTB, hnRNP H/F, SRSF6, RBM4) coordinate to produce tissue-appropriate isoform ratios in vivo.
  • No high-resolution cryo-EM structure of non-muscle TPM1 isoform on actin
  • Receptor or mechanism for extracellular TPM1 signaling unknown
  • Integrated in vivo model of combinatorial splicing regulation of TPM1 lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 7 GO:0005198 structural molecule activity 4
Localization
GO:0005856 cytoskeleton 5 GO:0005576 extracellular region 2 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-397014 Muscle contraction 10 R-HSA-1643685 Disease 9 R-HSA-8953854 Metabolism of RNA 4 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-109582 Hemostasis 1
Partners
ACT1ARHGAP11AEZH2MBNL1MYO2PTBRBM4TSPAN4
Complex memberships
actin cable (yeast)thin filament (tropomyosin-troponin-actin)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 miR-21 directly targets the 3'-UTR of TPM1 variants V1 and V5, suppressing TPM1 protein expression at the translational level (no change in mRNA), leading to reduced anchorage-independent growth suppression in breast cancer cells. Luciferase reporter assay with wild-type and deletion 3'-UTR constructs, Western blot, RT-PCR, 2D-DIGE proteomics The Journal of biological chemistry High 17363372
1992 Yeast TPM1 (tropomyosin) is required for directed vesicular transport to the cell surface; TPM1 disruption causes accumulation of late secretory vesicles and synthetic lethality with the myosin-V gene MYO2, placing TPM1 and actin cables in the same pathway as MYO2-dependent polarized secretion. Genetic disruption, epistasis with sec and myo2 mutations, electron microscopy, secretion assays The Journal of cell biology High 1629236
1995 Yeast Tpm2p (a second tropomyosin encoded by TPM2) spans four actin monomers whereas Tpm1p spans five; both compete for F-actin binding but perform non-redundant essential functions, as neither can substitute for the other in rescuing tpm1Δ growth or cell surface targeting defects. Biochemical purification, F-actin binding competition assays, genetic complementation, overexpression studies The Journal of cell biology High 7844152
2003 Mdm20p, acting cooperatively with the NatB acetyltransferase catalytic subunit Nat3p, mediates N-terminal acetylation of yeast Tpm1p; unacetylated Tpm1p shows severely reduced F-actin binding activity, establishing that N-terminal acetylation is required for Tpm1p association with and stabilization of actin filaments and cables. In vivo acetylation assays, F-actin co-sedimentation, genetic epistasis, biochemical characterization of Mdm20p/NatB interaction Proceedings of the National Academy of Sciences of the United States of America High 12808144
2000 Suppressor mutations in TPM1 and ACT1 (actin) rescue mdm20Δ defects in temperature-sensitive growth, mitochondrial inheritance, and actin cable formation; ACT1 mutations cluster in the actin region predicted to contact tropomyosin, indicating that enhanced actin-tropomyosin interactions stabilize actin cables. Suppressor screen, genetic epistasis, allele characterization Genetics Medium 11014803
2011 HCM-causing TPM1 mutations Asp175Asn and Glu180Gly shift tropomyosin strands further toward the open position on the thin filament and increase the proportion of strong-binding actomyosin sub-states during the ATPase cycle, providing a structural basis for increased Ca2+ sensitivity. Polarized fluorimetry of fluorescently labeled tropomyosin in ghost muscle fibers during ATPase cycle Biochimica et biophysica acta Medium 22155441
2011 The DCM-causing TPM1 Glu40Lys mutation reduces the proportion of strong-binding actomyosin sub-states during the ATPase cycle by inhibiting movements of actin subdomain-1 and the myosin SH1 helix at the AM**·ADP·Pi to AM transition, providing structural basis for contractile deficit in DCM. Polarized fluorimetry of fluorescently labeled proteins incorporated into ghost muscle fibers Biochemical and biophysical research communications Medium 21741356
2011 HCM-causing TPM1 mutations Asp175Asn and Glu180Gly shift tropomyosin further toward the open filament position and increase the affinity of tropomyosin for actin, with Glu180Gly having a greater effect, increasing strong cross-bridge binding during the ATPase cycle. Polarized fluorimetry with 5-iodoacetamide-fluorescein-labeled tropomyosin in ghost muscle fibers Biochemical and biophysical research communications Medium 21376702
2013 MBNL1 binds UGC/CUG motif clusters in the rat Tpm1 pre-mRNA and cooperates with PTB to repress exon 3 splicing in smooth muscle; MBNL1 N-terminal CCCH zinc-finger domains are sufficient for repression, and RNA binding by MBNL1 promotes a direct protein-protein interaction with PTB via an apparent conformational change. RNA binding assays, MBNL1 domain deletion analysis, protein-protein interaction assays, single molecule analysis of PTB binding cooperativity Nucleic acids research High 23511971
2008 A G-rich silencer element at the 5' end of a nonsense exon in the rat Tpm1 gene is bound by hnRNP H and F, which are required for skipping of this exon; computational predictions of enhancer/silencer elements within the nonsense exon were validated by systematic mutagenesis (11/13 mutations behaved as predicted). Mutagenesis of splicing regulatory elements, RNA binding assays for hnRNP H/F RNA (New York, N.Y.) High 19037011
2014 Seven HCM- and DCM-associated TPM1 mutations (E62Q, D84N, I172T, L185R, S215L, D230N, M281T) show mechanistic heterogeneity: HCM mutations increase Ca2+ sensitivity of cardiac myosin ATPase activity (hypersensitivity) while DCM mutations decrease it (hyposensitivity); mutations also alter protein stability and protein-protein interactions differentially. Ca2+ sensitivity of human β-cardiac myosin ATPase activity, fluorescent probe measurement of TnC conformational changes, thermal stability assays, protein interaction assays The Journal of biological chemistry High 25548289
2016 TPM1 mutations Arg167His, Arg167Gly, and Lys168Glu (in a consensus actin-binding site) alter azimuthal movement of tropomyosin on actin: Arg167Gly and Lys168Glu shift TM toward the filament centre (increasing the proportion of switched-on actin and strong-binding myosin heads even at relaxation), while Arg167His shifts TM toward the periphery (reducing these), demonstrating that TM-actin contacts are critical for thin filament regulation. Fluorescence polarization of labeled S1, actin, and tropomyosin in ghost muscle fibers during ATPase cycle Archives of biochemistry and biophysics Medium 27480605
2017 A natural antisense lncRNA (TPM1-AS), transcribed from the fourth intronic region of TPM1, binds RBM4 in the nucleus and inhibits RBM4-mediated inclusion of exon 2a in TPM1 pre-mRNA, resulting in specific downregulation of TPM1 variants V2 and V7, which in turn promotes filopodium formation and migration in esophageal cancer cells. In situ hybridization, RNA immunoprecipitation (RIP), knockdown/overexpression, alternative splicing analysis The international journal of biochemistry & cell biology Medium 28754317
2019 miR-183-5p.1 directly targets the 3'-UTR of TPM1 (confirmed by luciferase reporter assay), suppresses TPM1 protein expression, and promotes migration and invasion of gastric cancer AGS cells; TPM1 knockdown mimics and TPM1 overexpression reverses miR-183-5p.1-driven effects. Luciferase reporter assay, Western blot, Transwell migration/invasion assay, flow cytometry Oncology reports Medium 31638242
2021 The HCM-associated TPM1 E192K mutation causes loss of Ca2+-dependent crossbridge inhibition (increased residual crossbridge activity at low Ca2+), leading to cellular hypertrophy and diastolic dysfunction in patient-derived engineered heart tissues; chronic treatment with the myosin inhibitor mavacamten reversed hypertrophy, confirming that excess crossbridge activity is the pathogenic mechanism. Molecular dynamics, in vitro motility assay, multiscale computational modeling, patient iPSC-derived engineered heart tissues, mavacamten pharmacological rescue The Journal of general physiology High 34319370
2021 LINC01116 recruits EZH2 to the TPM1 promoter, causing H3K27me3-mediated transcriptional silencing of TPM1, which promotes colorectal cancer cell proliferation and angiogenesis. RNA pull-down, RIP, ChIP assay for EZH2 and H3K27me3 at TPM1 promoter, loss-of-function assays Journal of translational medicine Medium 33499872
2021 ARHGAP11A physically interacts with TPM1 (co-immunoprecipitation) and promotes malignant progression of gastric cancer cells by affecting actin filament stability and cell migration/invasion through this interaction. Co-immunoprecipitation, knockdown/overexpression, in vitro migration/invasion assays, in vivo xenograft Journal of oncology Medium 34912455
2021 ORMDL3 selectively expressed in airway smooth muscle increases TPM1 and TPM4 protein levels; siRNA knockdown of TPM1 specifically impairs ORMDL3-mediated ASM proliferation (hyperplasia) but not hypertrophy, placing TPM1 downstream of ORMDL3 in the control of smooth muscle cell proliferation. Transgenic mouse model, siRNA knockdown, FACS, BrdU incorporation, Western blot JCI insight Medium 33661765
2022 TPM1 drives LPS-induced neuroinflammation in retinal microglia via the PKA/CREB signaling pathway, and acts downstream of TREM2; in TREM2-/- retinas, TPM1 knockdown exaggerates inflammation, while in WT retinas it is anti-inflammatory, identifying TREM2 as a negative regulator of TPM1-mediated inflammatory signaling. siRNA knockdown, TREM2 KO mice, RNA sequencing, Western blot, qPCR, immunocytochemistry, electroretinogram Journal of neuroinflammation Medium 36241997
2022 Systemic TPM1 (elevated in aging plasma) induces neuroinflammation and ectopic dendritic sprouting in young mouse retinas via phosphorylation of PKA and regulation of the FABP5/NF-κB signaling pathway; depletion of TPM1 from old plasma abolishes its pro-aging effect, establishing TPM1 as a secreted systemic pro-aging factor. Heterochronic parabiosis, blood plasma transfer, recombinant protein administration, neutralizing antibody, proteomics, Western blot Aging cell Medium 35148456
2023 AZGP1P2 binds both UBA1 and RBM15; UBA1-mediated ubiquitination promotes RBM15 protein degradation, and RBM15 (as an m6A 'writer') controls m6A-dependent mRNA decay of TPM1, thereby regulating prostate cancer stem cell stemness and docetaxel sensitivity. RNA pull-down with mass spectrometry, co-immunoprecipitation, RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP), xenograft model, patient-derived organoids Research (Washington, D.C.) Medium 37854295
2023 The HCM-associated TPM1 S215L mutation destabilizes the blocked regulatory state and increases tropomyosin flexibility (molecular dynamics); in vitro motility showed increased Ca2+ sensitivity; engineered heart tissues with TPM1 S215L exhibited hypercontractility, hypertrophic gene upregulation, and diastolic dysfunction, confirming an inability to inhibit actomyosin interactions as the pathogenic mechanism. Molecular dynamics simulations, Markov model of thin filament activation, in vitro motility assay, 3D engineered heart tissues, gene expression analysis PNAS nexus High 36896133
2022 A dominant TPM1 mutation causing embryonic lethality in mice (disrupted myofibril assembly, no heartbeat) is suppressed in humans by a variant in TLN2 (another actin-binding protein); CRISPR knock-in of both TPM1 and TLN2 variants in mice rescues heart beating, demonstrating genetic suppression of TPM1-mediated myofibril assembly defects. Patient iPSC-derived cardiomyocytes, mouse CRISPR knock-in, embryonic lethality rescue, myofilament assembly imaging Cell reports. Medicine High 35243414
2024 HCM-causing TPM1 E62Q and DCM-causing TPM1 E54K mutations drive divergent contractile phenotypes via distinct molecular mechanisms: E62Q reduces effective tropomyosin molecular stiffness and favors the 'closed' regulatory state increasing Ca2+ sensitivity, whereas E54K acts via long-range allosteric interactions to increase the association rate of the C-terminal troponin I mobile domain to tropomyosin/actin, reducing Ca2+ sensitivity. Computational simulations, stem cell-derived cardiomyocytes expressing mutations, myosin activity modulators (pharmacological rescue), gene expression analysis in engineered heart tissues The Journal of clinical investigation High 39436707
2024 The DCM-associated TPM1 M8R mutation increases tropomyosin chain flexibility and enhances affinity for the blocked/inactive state on actin (molecular dynamics); in vitro motility shows reduced Ca2+ sensitivity, maximum force, and cooperativity; human engineered heart tissues with M8R show depressed contractility and twitch duration in a dose-dependent manner, consistent with model predictions. Atomistic simulations, Markov model of cardiac thin filament, in vitro motility assay, adenoviral expression in human engineered heart tissues, isometric twitch force measurement Frontiers in physiology High 39282088
2024 The DCM-causing TPM1 K30E mutation decreases thermal stability of tropomyosin and its actin complex, and significantly reduces sliding velocity of regulated thin filaments over cardiac myosin across the full physiological Ca2+ range; molecular dynamics suggests K30E alters the actin monomer contact, hindering the weak-to-strong myosin head transition. Recombinant protein production, thermal stability assays, in vitro motility assay, molecular dynamics simulations International journal of molecular sciences High 39684770
2021 CRISPR-based activation of endogenous TPM1 expression in primary human coronary artery endothelial cells stabilizes the actin cytoskeleton, inhibits TNFα-induced inflammatory response, stabilizes cell-cell junctions by reducing VE-cadherin cleavage and maintaining α- and β-catenin levels, and reduces inflammatory activation and migration of coronary artery smooth muscle cells. CRISPR activation, immunofluorescence for F-actin and junctional proteins, Western blot, migration assay Frontiers in cell and developmental biology Medium 34604206
2021 EZH2 and FOXP1, recruited by lncRNA ELFN1-AS1 (which is transcriptionally activated by MYC), bind the TPM1 promoter region to impose epigenetic transcriptional silencing, thereby promoting colorectal cancer growth. ChIP assay, luciferase reporter, qRT-PCR, loss-of-function assays Molecular cancer research : MCR Medium 35857351
2018 Single-molecule TIRF microscopy of skeletal muscle tropomyosin Tpm1.1 on single actin filaments revealed distinct nucleation, elongation, and dissociation kinetics on both sides of the actin filament, providing quantitative parameters for Tpm1.1-actin polymer dynamics. Single-molecule TIRF microscopy with microfluidics, kymograph analysis of Tpm1.1 binding/dissociation on individual actin filaments PloS one Medium 30532204
2021 Structural and functional analyses of five cytoplasmic TPM1-encoded isoforms (Tpm1.5, 1.6, 1.7, 1.12, Tpm4.2) demonstrated that alternatively spliced N-terminal (1a2b or 1b), internal (6a or 6b), and C-terminal (9a, 9c, 9d) exons determine distinct thermal stabilities, F-actin affinities, and actin filament interactions in an isoform-specific manner. Recombinant protein purification, thermal stability assays, F-actin co-sedimentation, biochemical characterization International journal of molecular sciences Medium 34067970
2025 Non-muscle TPM1 isoforms (Tpm1.7, 1.8, 1.9) significantly inhibit cofilin-1 binding to F-actin (co-sedimentation assay); Tpm1.1, 1.8, and 1.6 most effectively prevent cofilin-1-induced depolymerization/severing of actin filaments; all studied TPM1 isoforms prevent cofilin-1-induced conformational changes in F-actin, demonstrating isoform-specific regulation of cofilin-1 activity. Co-sedimentation assays, viscometry, rhodamine-phalloidin displacement assay Biochemistry. Biokhimiia Medium 41067737
2025 TSPAN4 physically interacts with TPM1 (co-immunoprecipitation) and influences its expression and localization; this interaction affects cytoskeletal organization and drives vascular smooth muscle cell phenotypic switching from contractile to synthetic phenotype, promoting VSMC proliferation and migration; TSPAN4-deficient mice show reduced vascular neointimal formation after carotid artery ligation. Co-immunoprecipitation, Western blot, EdU assays, Transwell migration, in vivo carotid artery ligation in TSPAN4-deficient mice Clinical science (London, England : 1979) Medium 41004162
2025 TPM1 overexpression in non-small cell lung cancer cells inhibits proliferation, migration, and invasion while promoting apoptosis; TPM1 interacts with YAP1 (Co-IP confirmed by HitPredict database prediction), and overexpression of TPM1 down-regulates YAP1; overexpression of YAP1 partially rescues the anti-tumor effects of TPM1, placing TPM1 upstream of YAP1 in lung cancer suppression. Co-IP, Western blot, CCK-8, flow cytometry, Transwell assay, overexpression/rescue experiments Discover oncology Low 40515937
2025 High-fat/palmitic acid stimulation increases TPM1 expression in cardiomyocytes; TPM1 is transferred to cardiac fibroblasts via extracellular vesicles, activating the P53/SHISA5 signaling axis and inducing ER stress and autophagy, thereby promoting atrial structural remodeling and fibrosis. Proteomic and transcriptomic sequencing, extracellular vesicle isolation, immunoblotting, immunohistochemistry, immunofluorescence, in vivo high-fat diet model Lipids in health and disease Medium 40221727
2026 CircNSD2 acts as a scaffold to enhance interaction between SRSF6 and USP10, preventing K48-linked polyubiquitination of SRSF6 at lysine 16 and blocking its proteasomal degradation; stabilized SRSF6 then reprograms TPM1 alternative splicing, promoting TNBC metastasis. RNA pulldown, proteomic analysis, RNA immunoprecipitation, ubiquitination assay, alternative splicing analysis Molecular cancer Medium 41808072
2025 Conditional ablation of Tpm1 in hematopoietic cells (Vav-Cre) or endothelium (Cdh5-Cre) reveals that Tpm1 is required for platelet adhesion to fibronectin and fibrinogen, clot contraction, and prevention of thrombotic vascular occlusion; Tpm1KO increases platelet lifespan explaining GWAS-linked increased platelet count. Conditional knockout mice (Vav-Cre and Cdh5-Cre), platelet adhesion assay, clot contraction assay, ferric chloride-induced stroke model in vivo bioRxivpreprint Medium

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). The Journal of biological chemistry 879 17363372
2010 Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy. Circulation. Cardiovascular genetics 199 20215591
1992 Characterization of TPM1 disrupted yeast cells indicates an involvement of tropomyosin in directed vesicular transport. The Journal of cell biology 145 1629236
1995 Tropomyosin is essential in yeast, yet the TPM1 and TPM2 products perform distinct functions. The Journal of cell biology 125 7844152
2003 Mdm20 protein functions with Nat3 protein to acetylate Tpm1 protein and regulate tropomyosin-actin interactions in budding yeast. Proceedings of the National Academy of Sciences of the United States of America 88 12808144
2009 [Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy]. Revista espanola de cardiologia 58 19150014
2018 Long non-coding RNA MEG3 suppresses the development of bladder urothelial carcinoma by regulating miR-96 and TPM1. Cancer biology & therapy 48 30461333
2003 Variable clinical manifestation of a novel missense mutation in the alpha-tropomyosin (TPM1) gene in familial hypertrophic cardiomyopathy. Journal of the American College of Cardiology 44 12651045
2017 Natural antisense transcript TPM1-AS regulates the alternative splicing of tropomyosin I through an interaction with RNA-binding motif protein 4. The international journal of biochemistry & cell biology 42 28754317
2014 Mechanistic heterogeneity in contractile properties of α-tropomyosin (TPM1) mutants associated with inherited cardiomyopathies. The Journal of biological chemistry 42 25548289
2023 AZGP1P2/UBA1/RBM15 Cascade Mediates the Fate Determinations of Prostate Cancer Stem Cells and Promotes Therapeutic Effect of Docetaxel in Castration-Resistant Prostate Cancer via TPM1 m6A Modification. Research (Washington, D.C.) 41 37854295
2021 LINC01116 facilitates colorectal cancer cell proliferation and angiogenesis through targeting EZH2-regulated TPM1. Journal of translational medicine 39 33499872
2019 miRNA‑183‑5p.1 promotes the migration and invasion of gastric cancer AGS cells by targeting TPM1. Oncology reports 38 31638242
2010 Identification of a novel TPM1 mutation in a family with left ventricular noncompaction and sudden death. Molecular genetics and metabolism 38 20965760
2021 Inhibition of cancer cell-derived exosomal microRNA-183 suppresses cell growth and metastasis in prostate cancer by upregulating TPM1. Cancer cell international 37 33653339
2013 MBNL1 and PTB cooperate to repress splicing of Tpm1 exon 3. Nucleic acids research 36 23511971
2009 Presence of activating KRAS mutations correlates significantly with expression of tumour suppressor genes DCN and TPM1 in colorectal cancer. BMC cancer 36 19678923
2020 The MicroRNA MiR-29c Alleviates Renal Fibrosis via TPM1-Mediated Suppression of the Wnt/β-Catenin Pathway. Frontiers in physiology 35 32346368
1999 Tpm1, a locus controlling IL-12 responsiveness, acts by a cell-autonomous mechanism. Journal of immunology (Baltimore, Md. : 1950) 34 9973388
2002 A novel TPM1 mutation in a family with hypertrophic cardiomyopathy and sudden cardiac death in childhood. The American journal of cardiology 33 12423715
2019 Thin filament dysfunctions caused by mutations in tropomyosin Tpm3.12 and Tpm1.1. Journal of muscle research and cell motility 32 31270709
2000 Suppressors of mdm20 in yeast identify new alleles of ACT1 and TPM1 predicted to enhance actin-tropomyosin interactions. Genetics 29 11014803
2022 TPM1 mediates inflammation downstream of TREM2 via the PKA/CREB signaling pathway. Journal of neuroinflammation 27 36241997
2021 Loss of crossbridge inhibition drives pathological cardiac hypertrophy in patients harboring the TPM1 E192K mutation. The Journal of general physiology 27 34319370
2020 Circ0001320 inhibits lung cancer cell growth and invasion by regulating TNFAIP1 and TPM1 expression through sponging miR-558. Human cell 27 33128699
2015 Coexistence of Digenic Mutations in Both Thin (TPM1) and Thick (MYH7) Filaments of Sarcomeric Genes Leads to Severe Hypertrophic Cardiomyopathy in a South Indian FHCM. DNA and cell biology 25 25607779
2022 Accumulation of systematic TPM1 mediates inflammation and neuronal remodeling by phosphorylating PKA and regulating the FABP5/NF-κB signaling pathway in the retina of aged mice. Aging cell 24 35148456
2020 Inhibition of miR-96 enhances the sensitivity of colorectal cancer cells to oxaliplatin by targeting TPM1. Experimental and therapeutic medicine 24 32765688
2021 CRISPR-Based Activation of Endogenous Expression of TPM1 Inhibits Inflammatory Response of Primary Human Coronary Artery Endothelial and Smooth Muscle Cells Induced by Recombinant Human Tumor Necrosis Factor α. Frontiers in cell and developmental biology 23 34604206
2012 Genetic and epigenetic alterations are involved in the regulation of TPM1 in cholangiocarcinoma. International journal of oncology 23 23254774
2016 Functional Assessment of Clubfoot Associated HOXA9, TPM1, and TPM2 Variants Suggests a Potential Gene Regulation Mechanism. Clinical orthopaedics and related research 21 27020427
2013 Somatic MYH7, MYBPC3, TPM1, TNNT2 and TNNI3 mutations in sporadic hypertrophic cardiomyopathy. Circulation journal : official journal of the Japanese Circulation Society 20 23782526
1995 Assignment of the human skeletal muscle alpha-tropomyosin gene (TPM1) to band 15q22 by fluorescence in situ hybridization. Cytogenetics and cell genetics 20 7835079
2015 Silencing of the TPM1 gene induces radioresistance of glioma U251 cells. Oncology reports 18 25873252
2021 Structural and Functional Peculiarities of Cytoplasmic Tropomyosin Isoforms, the Products of TPM1 and TPM4 Genes. International journal of molecular sciences 17 34067970
2011 The effect of the Asp175Asn and Glu180Gly TPM1 mutations on actin-myosin interaction during the ATPase cycle. Biochimica et biophysica acta 14 22155441
2022 MYC-Induced Upregulation of Lncrna ELFN1-AS1 Contributes to Tumor Growth in Colorectal Cancer via Epigenetically Silencing TPM1. Molecular cancer research : MCR 13 35857351
2017 Hypoxia and hyperoxia differentially control proliferation of rat neural crest stem cells via distinct regulatory pathways of the HIF1α-CXCR4 and TP53-TPM1 proteins. Developmental dynamics : an official publication of the American Association of Anatomists 13 28002632
2017 Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1 mutation. European journal of medical genetics 13 29024827
2008 A nonsense exon in the Tpm1 gene is silenced by hnRNP H and F. RNA (New York, N.Y.) 13 19037011
2021 ORMDL3 expression in ASM regulates hypertrophy, hyperplasia via TPM1 and TPM4, and contractility. JCI insight 12 33661765
1993 Chromosomal localization and genomic cloning of the mouse alpha-tropomyosin gene Tpm-1. Genomics 12 8406508
2021 Knockdown of LncRNA NEAT1 inhibits myofibroblast activity in oral submucous fibrosis through miR-760/TPM1 axis. Journal of dental sciences 11 35756787
2011 The effect of the dilated cardiomyopathy-causing Glu40Lys TPM1 mutation on actin-myosin interactions during the ATPase cycle. Biochemical and biophysical research communications 11 21741356
2023 CaMKII regulates the proteins TPM1 and MYOM2 and promotes diacetylmorphine-induced abnormal cardiac rhythms. Scientific reports 10 37037889
2022 Genetic resiliency associated with dominant lethal TPM1 mutation causing atrial septal defect with high heritability. Cell reports. Medicine 10 35243414
2021 ARHGAP11A Promotes the Malignant Progression of Gastric Cancer by Regulating the Stability of Actin Filaments through TPM1. Journal of oncology 10 34912455
2023 Mechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TPM1 variant S215L. PNAS nexus 9 36896133
2020 A novel homozygous TPM1 mutation in familial pediatric hypertrophic cardiomyopathy and in silico screening of potential targeting drugs. European review for medical and pharmacological sciences 8 32744700
2016 TPM1 polymorphisms and nonsyndromic orofacial clefts susceptibility in a Chinese Han population. American journal of medical genetics. Part A 8 26792422
2024 Distinct mechanisms drive divergent phenotypes in hypertrophic and dilated cardiomyopathy-associated TPM1 variants. The Journal of clinical investigation 6 39436707
2021 Generation of a TPM1 homozygous knockout embryonic stem cell line by CRISPR/Cas9 editing. Stem cell research 6 34352617
2019 Association of single nucleotide polymorphisms in the 3'UTR region of TPM1 gene with dilated cardiomyopathy: A case-control study. Medicine 6 31689804
2018 Interactions of tropomyosin Tpm1.1 on a single actin filament: A method for extraction and processing of high resolution TIRF microscopy data. PloS one 6 30532204
2014 Expression of TPM1κ, a Novel Sarcomeric Isoform of the TPM1 Gene, in Mouse Heart and Skeletal Muscle. Molecular biology international 6 24876965
2023 Immunohistochemical Expression of CD90, CD133, and TPM1 in Relation to Gastric Cancer and H. pylori Association. Asian Pacific journal of cancer prevention : APJCP 5 37378943
2022 Identification of a novel missense mutation in the TPM1 gene via exome sequencing in a Chinese family with dilated cardiomyopathy: A case report and literature review. Medicine 5 35029218
2011 Hypertrophic cardiomyopathy-causing Asp175asn and Glu180gly Tpm1 mutations shift tropomyosin strands further towards the open position during the ATPase cycle. Biochemical and biophysical research communications 4 21376702
2024 Identification of a novel likely pathogenic TPM1 variant linked to hypertrophic cardiomyopathy in a family with sudden cardiac death. ESC heart failure 3 38874371
2024 Functional and Structural Properties of Cytoplasmic Tropomyosin Isoforms Tpm1.8 and Tpm1.9. International journal of molecular sciences 3 38999987
2022 Derivation of YCMi005-A, a human-induced pluripotent stem cell line, from a patient with dilated cardiomyopathy carrying missense variant in TPM1 (p. Glu192Lys). Stem cell research 3 35176663
2016 Abnormal movement of tropomyosin and response of myosin heads and actin during the ATPase cycle caused by the Arg167His, Arg167Gly and Lys168Glu mutations in TPM1 gene. Archives of biochemistry and biophysics 3 27480605
2024 Nanofiber-based delivery of evodiamine impedes malignant properties of intrahepatic cholangiocarcinoma cells by targeting HDAC4 and restoring TPM1 transcription. Human cell 2 39073525
2024 In silico and in vitro models reveal the molecular mechanisms of hypocontractility caused by TPM1 M8R. Frontiers in physiology 2 39282088
2018 Considering the downregulation of Tpm1.6 and Tpm1.7 in squamous cell carcinoma of esophagus as a potent biomarker. Personalized medicine 2 30259780
2016 [Corrigendum] Genetic and epigenetic alterations are involved in the regulation of TPM1 in cholangiocarcinoma. International journal of oncology 2 27779677
2025 High-fat stimulation induces atrial structural remodeling via the TPM1/P53/SHISA5 Axis. Lipids in health and disease 1 40221727
2025 TSPAN4 controls vascular smooth muscle cell phenotypic switching and intimal hyperplasia by targeting TPM1-regulated cytoskeletal organization. Clinical science (London, England : 1979) 1 41004162
2025 Effect of Non-Muscle Tropomyosin Isoforms Encoded by the TPM1 Gene on Cofilin-1 Activity toward Actin Filaments. Biochemistry. Biokhimiia 1 41067737
2024 Novel Mutation Lys30Glu in the TPM1 Gene Leads to Pediatric Left Ventricular Non-Compaction and Dilated Cardiomyopathy via Impairment of Structural and Functional Properties of Cardiac Tropomyosin. International journal of molecular sciences 1 39684770
2022 Generation of a heterozygous TPM1-E192K knock-in human induced pluripotent stem cell line using CRISPR/Cas9 system. Stem cell research 1 35917600
2022 A Novel TPM1 Mutation Causes Familial Hypertrophic Cardiomyopathy in an Indian Family: Genetic and Clinical Correlation. Indian journal of clinical biochemistry : IJCB 1 38223010
2021 Association Between TPM1 Gene Polymorphisms and Idiopathic Congenital Talipes Equinovarus Risk in a Chinese Population. Genetic testing and molecular biomarkers 1 33945307
2015 [TPM1 gene mutation is associated with dilated cardiomyopathy in Kazaks in Xinjiang]. Zhonghua xin xue guan bing za zhi 1 26420121
2026 TPM1-p.E181K mutation suppresses CaMKII/HDAC4 signaling pathway leading to pediatric restrictive cardiomyopathy. Frontiers in genetics 0 41568329
2026 CircNSD2 promotes metastasis and immune escape by increasing the USP10/SRSF6-mediated alternative splicing of TPM1 in TNBC. Molecular cancer 0 41808072
2025 Amplified TPM1 suppresses non-small cell lung cancer cells proliferation and metastasis. Discover oncology 0 40515937
2025 ELF3 regulates epithelial-mesenchymal transition through TPM1 and promotes the development of endometrial cancer. Cytotechnology 0 40611880
2025 Isoform Specificity of a Compound Targeting Actin Filaments Containing Tropomyosin Tpm1.8/1.9. Cytoskeleton (Hoboken, N.J.) 0 41085091
2025 Role of microRNA-183 based theranostics through targeting TPM1 in bladder cancer. Discover oncology 0 41231336
2025 The Evolutionarily Conserved TPM1 Super-Enhancer Drives Skeletal Muscle Regeneration via Mechanotransduction Signaling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41243274