Affinage

TPM3

Tropomyosin alpha-3 chain · UniProt P06753

Length
285 aa
Mass
33.0 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TPM3 encodes α-tropomyosin(slow), a coiled-coil actin-binding protein that regulates thin-filament function in slow (type 1) skeletal muscle fibers and stabilizes distinct F-actin populations in non-muscle cells (PMID:26307083, PMID:33807093). In muscle, TPM3 governs Ca2+-sensitivity and acto-myosin cross-bridge cycling specifically in type 1 fibers, and pathogenic mutations act dominant-negatively: heterozygous mutant protein incorporates into sarcomeres at roughly equal ratio with wild-type (PMID:20554445), reducing actin-binding affinity, weakening tropomodulin binding, and disrupting cofilin-2-dependent thin-filament turnover, producing slow-fiber-specific weakness and nemaline rod bodies (PMID:18716557, PMID:26307083, PMID:32797717, PMID:38003645). Because α-tropomyosin(slow) is expressed only in type 1 fibers, disease pathology is restricted to that fiber type while fast fibers are spared (PMID:10619715, PMID:26307083). Distinct low-molecular-weight TPM3 isoforms generated by alternative splicing of exon 6 and the C-terminal exon 9 have divergent actin-binding and structural properties (PMID:34339666); among these, Tpm3.1 stabilizes specific F-actin subpopulations at the axon initial segment, neuronal growth cones, the oocyte cortex, and tendon stress fibers, protecting these filaments from cofilin-mediated depolymerization (PMID:25483187, PMID:32344377, PMID:33807093, PMID:36129771). TPM3 mRNA is stabilized by PCBP1 binding to its 3'UTR (PMID:35287546), and during acentrosomal meiotic spindle assembly TPM3 is recruited to centromeres and spindle poles via the coiled-coil motif of RNF20 (PMID:38240347). Independently of its normal function, the TPM3 N-terminal coiled-coil domain drives constitutive activation of fused tyrosine kinases: chromosomal rearrangements producing TPM3-ALK and TPM3-NTRK1 (TRKA) chimeras generate cytoplasmic, constitutively tyrosine-phosphorylated oncoproteins whose kinase activity and transforming capacity depend on TPM3-mediated dimerization (PMID:10216106, PMID:10934142, PMID:25596129, PMID:7590742).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 Medium

    Establishing that TPM3 mutations cause congenital myopathy linked the gene to thin-filament regulation in muscle and pinpointed an N-terminal actin-binding residue as disease-critical.

    Evidence Genetic linkage and sequencing of a nemaline myopathy family identifying the M9R missense substitution

    PMID:7704029

    Open questions at the time
    • Actin-binding effect inferred from sequence context, not directly assayed
    • Did not explain fiber-type restriction of pathology
  2. 1995 High

    Mapping TPM3 to 1q22-q23 next to NTRK1, and sequencing the TPM3-NTRK1 inversion breakpoint, revealed that TPM3's N-terminus can be fused to a tyrosine kinase to create a constitutively phosphorylated oncoprotein.

    Evidence FISH chromosomal localization and genomic breakpoint sequencing with tyrosine-phosphorylation detection in thyroid carcinoma

    PMID:7590742 PMID:7956350

    Open questions at the time
    • Mechanism of constitutive kinase activation not defined
    • Did not test transforming capacity directly
  3. 1999 Medium

    A null TPM3 allele and fiber-type-restricted nemaline bodies established that disease pathology tracks the type 1 fiber-specific expression of α-tropomyosin(slow); concurrently TPM3-ALK was identified as a recurrent cytoplasmic fusion in lymphoma.

    Evidence Sequencing plus muscle immunohistochemistry of a homozygous nonsense mutation; RT-PCR cloning and IHC of t(1;2) TPM3-ALK

    PMID:10216106 PMID:10619715

    Open questions at the time
    • Dimerization mechanism of TPM3-ALK inferred, not assayed
    • Did not biochemically test how loss of protein causes rods
  4. 2000 High

    Demonstrating that the tropomyosin N-terminal coiled-coil fused to the ALK kinase domain confers constitutive kinase activity defined the molecular basis of TPM3-driven oncogenesis.

    Evidence Cloning of TPM3-ALK and TPM4-ALK fusions with kinase activity and tyrosyl-phosphorylation assays

    PMID:10934142

    Open questions at the time
    • Dimerization not directly measured
    • Downstream signaling pathways not mapped
  5. 2007 Medium

    Showing that TPM3-ALK interacts with endogenous tropomyosin and confers higher metastatic capacity connected the fusion's biology to cytoskeletal organization.

    Evidence Reciprocal co-immunoprecipitation and in vivo lung metastasis assay in mice

    PMID:17276053

    Open questions at the time
    • Mechanistic link between tropomyosin interaction and metastasis not resolved
    • Single lab
  6. 2008 High

    Defining the dominant-negative biochemistry of M9R — equal-ratio heterodimer formation, reduced tropomodulin binding, and disrupted actin networks — explained how a single mutant allele causes disease.

    Evidence 2D-PAGE, far Western for tropomodulin, and myoblast transfection/immunofluorescence

    PMID:18716557

    Open questions at the time
    • Did not measure contractile consequence in fibers
    • Did not address Ca2+-sensitivity directly
  7. 2010 Medium

    Quantifying that mutant protein constitutes ~50% of sarcomeric α-tropomyosin(slow) in patient muscle confirmed dominant-negative incorporation in vivo for a second mutation.

    Evidence 2D-gel electrophoresis of R168C patient muscle biopsies

    PMID:20554445

    Open questions at the time
    • Did not link protein ratio to force deficit
    • Single patient cohort
  8. 2011 Medium

    Postsynaptic localization of TPM3 in hippocampal neurons established that specific isoforms segregate to distinct actin populations in non-muscle, CNS contexts.

    Evidence Immunofluorescence localization versus pre/postsynaptic markers in mouse neurons

    PMID:22545181

    Open questions at the time
    • Functional role at synapses not tested
    • Isoform identity not fully resolved
  9. 2014 Medium

    Identifying a constitutively active TPM3-TRKA fusion sensitive to TRKA inhibition extended the oncogenic fusion paradigm to colorectal carcinoma and provided a druggable target.

    Evidence Genomic characterization plus TRKA-inhibitor phosphorylation assay and in vivo tumor model in KM12 cells

    PMID:24962792

    Open questions at the time
    • Dimerization not directly tested for this fusion
    • Single cell-line origin
  10. 2014 Medium

    Cortical localization and knockdown phenotypes in oocytes showed non-muscle Tpm3 protects cortical actin from cofilin-mediated depolymerization to enable asymmetric division.

    Evidence Immunostaining, siRNA knockdown, and constitutively active cofilin overexpression in mouse oocytes

    PMID:25483187

    Open questions at the time
    • Specific isoform not identified
    • Direct biochemistry of cofilin protection not shown here
  11. 2015 High

    Direct dimerization mapping established that oncogenic TPM3-ALK activation and transformation require the coiled-coil, with longer regions promoting dimer formation and downstream signaling.

    Evidence Truncation series, BN-PAGE dimerization assay, phospho-Western, and focus formation in NIH3T3

    PMID:25596129

    Open questions at the time
    • Structural basis of dimer-driven kinase activation not solved
    • Other fusion partners not compared
  12. 2015 High

    Linking reduced actin binding to a measurable contractile deficit specifically in slow fibers connected molecular defect to physiology of weakness.

    Evidence Single-fiber contractility, actin co-sedimentation, 2D-PAGE, and modelling of R168C

    PMID:26307083

    Open questions at the time
    • Did not resolve why fast fibers tolerate the protein
    • Cofilin turnover not addressed in this study
  13. 2016 Medium

    FRAP showing dynamic Tpm3.1 exchange largely uncoupled from actin turnover defined tropomyosin as an independently regulated decoration on filaments.

    Evidence FRAP in cultured cells and intravital microscopy with jasplakinolide treatment

    PMID:27977753

    Open questions at the time
    • Regulators of exchange not identified
    • Mechanism of exchange unknown
  14. 2020 Medium

    Tpm3.1 was shown to be required for axon-initial-segment actin patches and periodic actin rings, coupling a specific isoform to neuronal protein sorting and excitability.

    Evidence Immunofluorescence co-localization, pharmacological Tpm3.1 inhibition, and electrophysiology

    PMID:32344377

    Open questions at the time
    • Inhibitor specificity caveats
    • Direct molecular partners at AIS not defined
  15. 2021 High

    Knockout and C-terminal truncation studies established that the Tpm3.1 C-terminus drives stress-fiber and growth-cone actin maintenance required for neurite outgrowth, while in vitro reconstitution mapped distinct mutation mechanisms (tropomodulin affinity, cofilin-2 inhibition, Ca2+-sensitivity, dimer structure) and splice-isoform-specific actin properties.

    Evidence Tpm3 KO neurons with domain-deletion rescue; recombinant protein ATPase/co-sedimentation/polarized fluorescence; CD spectroscopy of isoforms

    PMID:32797717 PMID:33807093 PMID:34339666

    Open questions at the time
    • In vivo relevance of isoform diversity not fully tested
    • Combined effects of multiple regulators not reconstituted together
  16. 2022 Medium

    Demonstrating Tpm3.1-dependent F-actin maintenance in tenocytes and PCBP1-mediated TPM3 mRNA stabilization expanded TPM3's roles to tendon homeostasis and post-transcriptional regulation in cancer cell migration.

    Evidence G/F-actin assay with Tpm3.1 inhibition in tenocytes/explants; RIP and actinomycin D mRNA-stability assays with migration/invasion readouts in ESCC

    PMID:35287546 PMID:36129771

    Open questions at the time
    • Upstream control of Tpm3.1 expression under mechanical load incomplete
    • PCBP1-TPM3 axis tested in single cancer context
  17. 2023 High

    Reconstitution showed troponin and Tpm3.12 together inhibit cofilin-2 severing, and the R91C myopathy variant abnormally over-inhibits filament turnover, linking pathogenic mutation to defective actin dynamics.

    Evidence In vitro co-sedimentation, pyrene depolymerization, and cofilin-2 severing assays with recombinant proteins

    PMID:38003645

    Open questions at the time
    • In vivo confirmation in patient muscle absent
    • Did not connect altered turnover to force deficit directly
  18. 2024 Medium

    RNF20-mediated recruitment of TPM3 to centromeres and spindle poles and TPM3's protective role in hypoxic cardiomyocytes broadened its functions to meiotic spindle assembly and cytoskeletal stress protection.

    Evidence Co-IP and RNF20 depletion/E3-dead rescue in oocytes; TPM3 OE/KD with HDAC1-inhibitor rescue in cardiomyocyte hypoxia model

    PMID:38240347 PMID:38928503

    Open questions at the time
    • Isoform mediating spindle recruitment not specified
    • TPM3-HDAC1 mechanistic link not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How isoform-specific TPM3 decoration is targeted to and dynamically regulated across its many distinct F-actin populations, and how this integrates with binding partners (tropomodulin, cofilin-2, troponin, RNF20), remains incompletely defined.
  • No unifying structural model of isoform-specific filament selection
  • Regulators directing Tpm3.1 to specific cellular sites unknown
  • Mechanistic basis for fiber-type and tissue specificity not fully resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0005198 structural molecule activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 4 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-397014 Muscle contraction 2
Partners
ALKCOFILIN-2NTRK1PCBP1RNF20TROPOMODULINTROPONIN
Complex memberships
thin filament

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 A missense mutation (M9R) in TPM3 encoding α-tropomyosin(slow) substitutes an arginine for a highly conserved methionine near the N-terminus in a putative actin-binding site, and was proposed to strengthen tropomyosin-actin binding, leading to nemaline rod body formation in slow (type 1) muscle fibers. Genetic linkage analysis and DNA sequencing of a nemaline myopathy family; mutation identified in a putative actin-binding motif Nature genetics Medium 7704029
1999 Homozygosity for a nonsense mutation at codon 31 of TPM3 results in no functional α-tropomyosin(slow) protein; nemaline bodies were restricted exclusively to type 1 (slow) fibers, consistent with TPM3 expression only in type 1 fibers, establishing fiber-type-specific expression as essential to disease pathology. SSCP and DNA sequencing; muscle biopsy immunohistochemistry demonstrating fiber-type restriction of nemaline bodies Neuromuscular disorders : NMD Medium 10619715
1999 In anaplastic large cell lymphoma with t(1;2)(q25;p23), TPM3 fuses to ALK, producing a constitutively expressed TPM3-ALK chimeric protein that is restricted to the cytoplasm; the TPM3 coiled-coil domain mediates homodimerization of the fusion protein, leading to constitutive activation of ALK kinase. RT-PCR walking strategy to identify fusion partner; immunohistochemistry showing cytoplasmic ALK localization; mechanistic inference of homodimerization from TPM3 protein-protein interaction domain Blood Medium 10216106
2000 TPM3-ALK and TPM4-ALK oncoproteins (~95 kDa) are characterized by constitutive ALK kinase activity and tyrosyl-phosphorylation; the N-terminal coiled-coil domains of tropomyosin fused to the ALK C-terminal kinase domain drive constitutive activation. Cloning of fusion genes; immunohistochemistry and immunoprecipitation demonstrating constitutive kinase activity and tyrosyl-phosphorylation The American journal of pathology High 10934142
2007 TPM3-ALK expression specifically induces changes in cell morphology and cytoskeleton organisation, and confers higher metastatic capacity than other ALK fusion proteins; co-immunoprecipitation demonstrated a specific interaction between TPM3-ALK and endogenous tropomyosin. Experimental lung metastasis assay in mice; co-immunoprecipitation of TPM3-ALK with endogenous tropomyosin; cell morphology analysis European journal of cancer (Oxford, England : 1990) Medium 17276053
2008 The M9R mutation in TPM3 causes nemaline bodies restricted to atrophied type 1 fibers; α-tropomyosin(slow) is not expressed at significant levels until after birth; wild-type and M9R mutant α-tropomyosin(slow) form heterodimers in equal ratio (dominant-negative); M9R greatly reduced binding affinity of tropomodulin for α-tropomyosin(slow) compared to wild-type; M9R mutant reduced incorporation into stress fibers and disrupted filamentous actin networks in transfected myoblasts. Protein analysis (isoelectric focusing, 2D-PAGE); far Western blot for tropomodulin binding; transfection of mutant and wild-type constructs into myoblasts; immunofluorescence Journal of neuropathology and experimental neurology High 18716557
2010 2D-gel electrophoresis of patient muscle showed that mutant α-tropomyosin(slow) accounts for ~50% of α-tropomyosin(slow) in sarcomeres in patients with p.R168C TPM3 mutation, consistent with a dominant-negative mechanism of disease pathogenesis. 2D-gel electrophoresis of patient muscle biopsies Neuromuscular disorders : NMD Medium 20554445
2011 TPM3 (and TPM4) gene products localize specifically to the postsynaptic region (not presynaptic) in mouse hippocampal neurons, establishing isoform-specific segregation to distinct actin filament populations at CNS synapses. Immunofluorescence localization in mouse hippocampal neurons; comparison with pre- and postsynaptic markers Bioarchitecture Medium 22545181
2014 TPM3-NTRK1 rearrangement produces a constitutively active chimeric TPM3-TRKA kinase in colorectal carcinoma cell line KM12; TRKA kinase inhibitor NMS-P626 suppressed TPM3-TRKA phosphorylation and downstream signaling, confirming constitutive kinase activation by the fusion. Genomic characterization of rearrangement; phosphorylation assay with TRKA inhibitor; in vivo tumor model Molecular oncology Medium 24962792
2014 Non-muscle Tpm3 protein localizes at the cortex of mouse oocytes during germinal vesicle and GVB stages; knockdown of Tpm3 impaired asymmetric division, spindle migration, reduced cortical actin, and caused membrane blebbing; Tpm3 protects cortical actin from cofilin-mediated depolymerization. Immunostaining, siRNA knockdown, overexpression of constitutively active cofilin mutant in mouse oocytes; confocal imaging of actin Cell cycle (Georgetown, Tex.) Medium 25483187
2015 Oncogenic TPM3-ALK activation requires dimerization mediated through the coiled-coil structure of TPM3; longer TPM3 regions led to higher dimer formation (BN-PAGE); phosphorylation of ALK, ERK1/2, and STAT3 depended on TPM3-ALK dimerization; NIH3T3 cells expressing full-length TPM3-ALK lost contact inhibition (focus formation) while ALK alone did not transform. Lentiviral expression of truncation constructs; Blue-native PAGE (BN-PAGE) for dimerization; Western blot for phosphorylation; focus formation assay Biochemical and biophysical research communications High 25596129
2015 Muscle weakness in TPM3-myopathy patients is directly attributable to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling kinetics specifically in slow (type 1) myofibers; co-sedimentation assays showed reduced binding of mutant R168C α-tropomyosin(slow) to filamentous actin; at physiological [Ca2+], patient slow fibers produced only 26% of control force; fast fibers were spared. Single fiber contractility studies; co-sedimentation actin-binding assay; 2D-PAGE; molecular modelling Human molecular genetics High 26307083
2016 Tpm3.1 (a TPM3 isoform) undergoes continuous dynamic exchange in actin filament bundles; FRAP analysis showed 50-70% mobile fraction; exchange of Tpm3.1 is largely independent of actin filament assembly/turnover (jasplakinolide stabilization of actin did not significantly affect Tpm3.1 exchange). FRAP analysis of fluorescently tagged Tpm3.1 in cultured cells and in vivo (intravital microscopy in rats); treatment with jasplakinolide PloS one Medium 27977753
2020 Tpm3.1 (TPM3 isoform) co-localizes with actin patches at the axon initial segment (AIS); pharmacological inhibition of Tpm3.1 reduced density of actin patches, disrupted periodicity of sub-membranous actin rings, reduced accumulation of AIS structural/functional proteins, disrupted axonal/somatodendritic protein sorting, and reduced neuronal firing frequency. Immunofluorescence co-localization; pharmacological Tpm3.1 inhibition; electrophysiology; live imaging iScience Medium 32344377
2021 Knockout of Tpm3 in hippocampal neurons decreased neurite length and complexity; deletion of C-terminal residues of Tpm3.1 impaired its association with stress fibers and its segregation to neurite tips, and abolished its ability to maintain the filamentous actin pool at axonal growth cones. Primary neurons from Tpm3 knockout mice; morphometric analysis; expression of C-terminal truncation mutants; immunofluorescence Cells Medium 33807093
2021 M9R mutation in Tpm3.12 impairs acto-myosin cross-bridge cycling; at molecular level, M9R reduces tropomodulin affinity for α-tropomyosin(slow) and disrupts cofilin-2 inhibition; E151A mutation alters Ca2+-sensitivity of thin filaments; K169E mutation directly affects tropomyosin dimer structure-function; γγ-homodimers and γβ-heterodimers show distinct responses depending on which chain carries the mutation. Recombinant protein production; actin co-sedimentation; in vitro ATPase assay; polarized fluorescence microscopy of reconstituted thin filaments in ghost fibers FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 32797717
2021 Five low molecular weight TPM3 isoforms (Tpm3.1, 3.2, 3.4, 3.5, 3.7) differ in actin-binding and structural properties depending on alternatively spliced exon 6 (6a or 6b) and C-terminal exon 9 (9a, 9c, or 9d), demonstrating that alternative splicing determines distinct cytoskeletal functions. Biochemical characterization including CD spectroscopy, thermal stability assays, actin co-sedimentation of recombinant isoforms Archives of biochemistry and biophysics Medium 34339666
2022 Tpm3.1 (TPM3 isoform) associates with F-actin in tenocytes; Tpm3.1 inhibition reduces F-actin levels in tendons, decreases tenogenic gene expression, increases chondrogenic and protease (MMP-3) expression, consistent with tendinosis progression; mechanical stress deprivation reduces F-actin through downregulation of Tpm3.1. G/F-actin ratio assay; pharmacological Tpm3.1 inhibition in mouse and human tenocytes and ex vivo tendon explants; RT-PCR for gene expression Molecular biology of the cell Medium 36129771
2022 PCBP1 (PolyC-RNA-binding protein 1) directly binds the 3'UTR of TPM3 mRNA (verified by RNA immunoprecipitation) and stabilizes TPM3 mRNA; PCBP1 knockdown reduced TPM3 mRNA stability (accelerated degradation after actinomycin D treatment), and reduced TPM3-dependent migration and invasion in ESCC cells. RNA-protein immunoprecipitation (RIP); actinomycin D mRNA stability assay; Western blot; migration/invasion assays Bioengineered Medium 35287546
2023 Troponin complex inhibits cofilin-2-mediated severing and depolymerization of actin filaments decorated with Tpm3.12; the myopathy-causing R91C variant of Tpm3.12 was more resistant to removal by cofilin-2 and more strongly inhibited cofilin-2-dependent actin filament turnover compared to wild-type, indicating the pathogenic variant impairs actin filament dynamics. In vitro actin co-sedimentation; pyrene actin depolymerization assays; cofilin-2 severing assay with recombinant proteins International journal of molecular sciences High 38003645
2024 RNF20 recruits TPM3 to both centromeres and spindle poles during acentrosomal meiotic spindle assembly in mouse oocytes; this recruitment is mediated by RNF20's coiled-coil motif (not its E3 ligase activity); RNF20-depleted oocytes show abnormal spindle and chromosome misalignment that can be attributed to loss of TPM3 recruitment. Co-immunoprecipitation; localization by immunofluorescence; RNF20 depletion and E3 ligase-dead mutant rescue in mouse oocytes Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 38240347
2024 TPM3 overexpression attenuated hypoxia-induced morphological changes, cytoskeletal disruption, oxidative stress, and LDH release in cardiomyocytes; TPM3 knockdown exacerbated these effects; HDAC1 inhibitor (MGCD0103) partially reversed the exacerbation caused by TPM3 knockdown, linking TPM3 to HDAC1-regulated cytoskeletal stability. Lentiviral TPM3 overexpression and knockdown in AC16/H9c2 cells; CoCl2 hypoxia model; LDH, MDA, SOD assays; HDAC1 inhibitor treatment International journal of molecular sciences Medium 38928503
1995 The TPM3 gene was localized to chromosome 1q22→q23 by FISH, placing it in close proximity to NTRK1 (1q23→q24) and within the NEM1 locus, establishing the chromosomal basis for the recurring TPM3-NTRK1 intrachromosomal inversion in papillary thyroid carcinoma. Fluorescence in situ hybridization (FISH) using sequence-tagged sites Cytogenetics and cell genetics Medium 7956350
1995 TPM3-NTRK1 gene fusion results from an intrachromosomal inversion at chromosome 1; the chimeric protein (70 kDa) consists of the 221 N-terminal residues of TPM3 fused to NTRK1, is constitutively phosphorylated on tyrosine, and identical breakpoints produce an invariable transcript in all tumors. Genomic sequencing of breakpoints; RT-PCR; tyrosine phosphorylation detection Genomics High 7590742

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. The American journal of pathology 534 10934142
1995 A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy. Nature genetics 265 7704029
1999 A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. Blood 245 10216106
2014 The TPM3-NTRK1 rearrangement is a recurring event in colorectal carcinoma and is associated with tumor sensitivity to TRKA kinase inhibition. Molecular oncology 139 24962792
2008 EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. Lung cancer (Amsterdam, Netherlands) 135 18242762
2008 Mutations in TPM3 are a common cause of congenital fiber type disproportion. Annals of neurology 120 18300303
1999 Homozygosity for a nonsense mutation in the alpha-tropomyosin slow gene TPM3 in a patient with severe infantile nemaline myopathy. Neuromuscular disorders : NMD 95 10619715
2014 Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies. Human mutation 92 24692096
1995 A sequence analysis of the genomic regions involved in the rearrangements between TPM3 and NTRK1 genes producing TRK oncogenes in papillary thyroid carcinomas. Genomics 89 7590742
2002 Mutations of the slow muscle alpha-tropomyosin gene, TPM3, are a rare cause of nemaline myopathy. Neurology 72 12196661
2010 Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion. Human mutation 62 19953533
2014 TORC1 regulates Pah1 phosphatidate phosphatase activity via the Nem1/Spo7 protein phosphatase complex. PloS one 52 25117580
2014 Yeast Nem1-Spo7 protein phosphatase activity on Pah1 phosphatidate phosphatase is specific for the Pho85-Pho80 protein kinase phosphorylation sites. The Journal of biological chemistry 52 25359770
2010 Congenital fibre type disproportion associated with mutations in the tropomyosin 3 (TPM3) gene mimicking congenital myasthenia. Neuromuscular disorders : NMD 52 20951040
2018 The Nem1/Spo7-Pah1/lipin axis is required for autophagy induction after TORC1 inactivation. The FEBS journal 51 29604183
2007 TPM3-ALK expression induces changes in cytoskeleton organisation and confers higher metastatic capacities than other ALK fusion proteins. European journal of cancer (Oxford, England : 1990) 46 17276053
2019 Delivery of platelet TPM3 mRNA into breast cancer cells via microvesicles enhances metastasis. FEBS open bio 45 31705785
2015 Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres. Human molecular genetics 44 26307083
2016 TFE3-positive renal cell carcinomas are not always Xp11 translocation carcinomas: Report of a case with a TPM3-ALK translocation. Pathology, research and practice 42 27450657
2007 A second pedigree with autosomal dominant nemaline myopathy caused by TPM3 mutation: a clinical and pathological study. Neuromuscular disorders : NMD 41 17376686
2009 A TPM3 mutation causing cap myopathy. Neuromuscular disorders : NMD 36 19553118
2018 The TORC1-Nem1/Spo7-Pah1/lipin axis regulates microautophagy induction in budding yeast. Biochemical and biophysical research communications 35 30201264
2019 Thin filament dysfunctions caused by mutations in tropomyosin Tpm3.12 and Tpm1.1. Journal of muscle research and cell motility 33 31270709
2008 Identification of a founder mutation in TPM3 in nemaline myopathy patients of Turkish origin. European journal of human genetics : EJHG 32 18382475
2021 TPM3 mediates epithelial-mesenchymal transition in esophageal cancer via MMP2/MMP9. Annals of translational medicine 31 34532475
2020 Tropomyosin Tpm3.1 Is Required to Maintain the Structure and Function of the Axon Initial Segment. iScience 29 32344377
2020 Suppression of long non-coding RNA MALAT1 inhibits survival and metastasis of esophagus cancer cells by sponging miR-1-3p/CORO1C/TPM3 axis. Molecular and cellular biochemistry 28 32468237
2002 De novo missense mutation in a constitutively expressed exon of the slow alpha-tropomyosin gene TPM3 associated with an atypical, sporadic case of nemaline myopathy. Neuromuscular disorders : NMD 27 12467750
2017 Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with the variant RNF213-, ATIC- and TPM3-ALK fusions is characterized by copy number gain of the rearranged ALK gene. Haematologica 26 28659337
2010 Conditional TPM3-ALK and NPM-ALK transgenic mice develop reversible ALK-positive early B-cell lymphoma/leukemia. Blood 26 20223922
2011 TPM3 and TPM4 gene products segregate to the postsynaptic region of central nervous system synapses. Bioarchitecture 25 22545181
2017 ALK-TPM3 rearrangement in adult renal cell carcinoma: Report of a new case showing loss of chromosome 3 and literature review. Cancer genetics 24 29405994
2013 Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene. Neuromuscular disorders : NMD 24 24095155
2008 Disease severity and thin filament regulation in M9R TPM3 nemaline myopathy. Journal of neuropathology and experimental neurology 23 18716557
2005 Inflammatory myofibroblastic tumor with ALK/TPM3 fusion presenting as ileocolic intussusception: an unusual presentation of an unusual neoplasm. Human pathology 23 16360423
2022 Phosphorylation-mediated regulation of the Nem1-Spo7/Pah1 phosphatase cascade in yeast lipid synthesis. Advances in biological regulation 22 35231723
2020 The Spo7 sequence LLI is required for Nem1-Spo7/Pah1 phosphatase cascade function in yeast lipid metabolism. The Journal of biological chemistry 22 32527729
2017 Proteomic analysis indicates the importance of TPM3 in esophageal squamous cell carcinoma invasion and metastasis. Molecular medicine reports 22 28138712
1995 Assignment of the human a-tropomyosin gene TPM3 to 1q22-->q23 by fluorescence in situ hybridisation. Cytogenetics and cell genetics 22 7956350
2015 Oncogenic TPM3-ALK activation requires dimerization through the coiled-coil structure of TPM3. Biochemical and biophysical research communications 21 25596129
2013 Novel TPM3 mutation in a family with cap myopathy and review of the literature. Neuromuscular disorders : NMD 21 24239060
2010 Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3. Neuromuscular disorders : NMD 21 20554445
2009 Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm. Human genetics 21 20024584
2018 Protein kinase A phosphorylates the Nem1-Spo7 protein phosphatase complex that regulates the phosphorylation state of the phosphatidate phosphatase Pah1 in yeast. The Journal of biological chemistry 20 30201607
2023 Tropomyosin 3 (TPM3) function in skeletal muscle and in myopathy. Skeletal muscle 18 37936227
2020 Sarcomeric TPM3 expression in human heart and skeletal muscle. Cytoskeleton (Hoboken, N.J.) 18 32761805
2022 Stress deprivation of tendon explants or Tpm3.1 inhibition in tendon cells reduces F-actin to promote a tendinosis-like phenotype. Molecular biology of the cell 17 36129771
2019 ALK-TPM3 rearrangement in adult renal cell carcinoma: a case report and literature review. Diagnostic pathology 17 31627758
2007 Development of a conditional bioluminescent transplant model for TPM3-ALK-induced tumorigenesis as a tool to validate ALK-dependent cancer targeted therapy. Cancer biology & therapy 17 17660712
2018 The Nem1-Spo7 protein phosphatase complex is required for efficient mitophagy in yeast. Biochemical and biophysical research communications 16 29305265
2022 Phosphatidic Acid Mediates the Nem1-Spo7/Pah1 Phosphatase Cascade in Yeast Lipid Synthesis. Journal of lipid research 15 36314526
2014 Non-muscle tropomyosin (Tpm3) is crucial for asymmetric cell division and maintenance of cortical integrity in mouse oocytes. Cell cycle (Georgetown, Tex.) 15 25483187
2006 A case of an inflammatory myofibroblastic tumor in the lung which expressed TPM3-ALK gene fusion. Pediatric surgery international 15 17063337
2018 The Primary Causes of Muscle Dysfunction Associated with the Point Mutations in Tpm3.12; Conformational Analysis of Mutant Proteins as a Tool for Classification of Myopathies. International journal of molecular sciences 14 30544720
2017 Dual drive coexistence of EML4-ALK and TPM3-ROS1 fusion in advanced lung adenocarcinoma. Thoracic cancer 14 29251824
2019 Protein kinase C mediates the phosphorylation of the Nem1-Spo7 protein phosphatase complex in yeast. The Journal of biological chemistry 13 31501244
2014 Frequency and phenotype of patients carrying TPM2 and TPM3 gene mutations in a cohort of 94 patients with congenital myopathy. Neuromuscular disorders : NMD 13 24507666
2024 The Role of TPM3 in Protecting Cardiomyocyte from Hypoxia-Induced Injury via Cytoskeleton Stabilization. International journal of molecular sciences 12 38928503
2022 ALK-rearranged renal cell carcinoma with TPM3::ALK gene fusion and review of the literature. Virchows Archiv : an international journal of pathology 12 36370168
2019 Research on the establishment of a TPM3 monoclonal stable transfected PANC-1 cell line and the experiment of the EMT occurrence in human pancreatic cancer. OncoTargets and therapy 12 31371995
2015 A Large Deletion Affecting TPM3, Causing Severe Nemaline Myopathy. Journal of neuromuscular diseases 12 27858751
2023 Conserved regions of the regulatory subunit Spo7 are required for Nem1-Spo7/Pah1 phosphatase cascade function in yeast lipid synthesis. The Journal of biological chemistry 11 37030502
2023 The Phosphatase Cascade Nem1/Spo7-Pah1 Regulates Fungal Development, Lipid Homeostasis, and Virulence in Botryosphaeria dothidea. Microbiology spectrum 10 37191532
2022 PolyC-RNA-binding protein 1 (PCBP1) enhances tropomyosin 3 (TPM3) mRNA stability to promote the progression of esophageal squamous cell carcinoma. Bioengineered 10 35287546
2020 Effects of myopathy-causing mutations R91P and R245G in the TPM3 gene on structural and functional properties of slow skeletal muscle tropomyosin. Biochemical and biophysical research communications 10 33307294
2016 Recruitment Kinetics of Tropomyosin Tpm3.1 to Actin Filament Bundles in the Cytoskeleton Is Independent of Actin Filament Kinetics. PloS one 10 27977753
2023 A cutaneous epithelioid vascular tumor harboring a TPM3::ALK fusion. Genes, chromosomes & cancer 9 37787425
2020 Mechanisms of disturbance of the contractile function of slow skeletal muscles induced by myopathic mutations in the tropomyosin TPM3 gene. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 32797717
2025 Cutaneous Hemangioma With Epithelioid Features Harboring TPM3/4::ALK Fusions : A Distinct Entity or a Molecular Variant of Epithelioid Hemangioma? The American journal of surgical pathology 8 40070162
2015 Ras Transformation Overrides a Proliferation Defect Induced by Tpm3.1 Knockout. Cellular & molecular biology letters 8 26274783
2015 NEM1 acts as a suppressor of apoptotic phenotypes in LSM4 yeast mutants. FEMS yeast research 8 26316593
2021 Deletion of the Actin-Associated Tropomyosin Tpm3 Leads to Reduced Cell Complexity in Cultured Hippocampal Neurons-New Insights into the Role of the C-Terminal Region of Tpm3.1. Cells 7 33807093
2021 Comparative structural and functional studies of low molecular weight tropomyosin isoforms, the TPM3 gene products. Archives of biochemistry and biophysics 7 34339666
2020 Characteristics of Renal Cell Carcinoma Harboring TPM3-ALK Fusion. Yonsei medical journal 7 32102128
2019 Congenital fiber type disproportion caused by TPM3 mutation: A report of two atypical cases. Neuromuscular disorders : NMD 7 31866162
2025 Renal cell carcinoma with ALK-TPM3 gene fusion and ALK amplification: A case report and literature review. Pathology, research and practice 6 39813766
2024 RNF20 Regulates Oocyte Meiotic Spindle Assembly by Recruiting TPM3 to Centromeres and Spindle Poles. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 6 38240347
2023 A lipid droplet-associated protein Nem1 regulates appressorium function for infection of Magnaporthe oryzae. aBIOTECH 6 37581021
2023 The Saccharomyces cerevisiae Spo7 basic tail is required for Nem1-Spo7/Pah1 phosphatase cascade function in lipid synthesis. The Journal of biological chemistry 6 38141768
2022 A rare case of recurrent ovarian cancer with TPM3-NTRK1 gene rearrangement: A case report. Molecular and clinical oncology 6 35251641
2022 MiR-107 inhibits the malignant biological behavior of esophageal squamous cell carcinoma by targeting TPM3. Journal of gastrointestinal oncology 6 36092346
2021 α-tropomyosin gene (TPM3) mutation in an infant with nemaline myopathy. Clinical case reports 6 33768912
2021 Molecular Mechanisms of the Deregulation of Muscle Contraction Induced by the R90P Mutation in Tpm3.12 and the Weakening of This Effect by BDM and W7. International journal of molecular sciences 6 34204776
2019 Genomic Profiling Reveals Synchronous Bilateral Lung Adenocarcinomas With Distinct Driver Alterations of EML4-ALK or TPM3-ROS1 Fusion: A Case Report. Frontiers in oncology 5 31828041
2023 Molecular Mechanisms of Deregulation of Muscle Contractility Caused by the R168H Mutation in TPM3 and Its Attenuation by Therapeutic Agents. International journal of molecular sciences 4 36982903
2023 Comparative Genomics Identifies the Evolutionarily Conserved Gene TPM3 as a Target of eca-miR-1 Involved in the Skeletal Muscle Development of Donkeys. International journal of molecular sciences 4 37895119
2023 Troponin and a Myopathy-Linked Mutation in TPM3 Inhibit Cofilin-2-Induced Thin Filament Depolymerization. International journal of molecular sciences 4 38003645
2022 Novel autosomal dominant TPM3 mutation causes a combined congenital fibre type disproportion-cap disease histological pattern. Neuromuscular disorders : NMD 4 35688744
2022 LncRNA WEE2-AS1 knockdown inhibits the proliferation, migration and invasion of glioma cells via regulating miR-29b-2-5p/TPM3 axis. Oncology research 4 37305396
2020 Demonstration of beta-tropomyosin (Tpm2) and duplication of the alpha-slow tropomyosin gene (TPM3) in Atlantic salmon Salmo salar. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 4 32283206
2020 Molecular Mechanisms of Muscle Weakness Associated with E173A Mutation in Tpm3.12. Troponin Ca2+ Sensitivity Inhibitor W7 Can Reduce the Damaging Effect of This Mutation. International journal of molecular sciences 4 32580284
2019 The molecular mechanisms of a high Ca2+-sensitivity and muscle weakness associated with the Ala155Thr substitution in Tpm3.12. Biochemical and biophysical research communications 4 31155291
2018 Small molecule targeting of the actin associating protein tropomyosin Tpm3.1 increases neuroblastoma cell response to inhibition of Rac-mediated multicellular invasion. Cytoskeleton (Hoboken, N.J.) 4 29752871
2018 A putative NEM1 homologue regulates lipid droplet biogenesis via PAH1 in Tetrahymena thermophila. Journal of biosciences 4 30207315
2024 Case report: Adult NTRK-rearranged spindle cell neoplasms with TPM3-NTRK1 fusion in the pelvic. Frontiers in oncology 3 38357202
2022 LncRNA WEE2-AS1 Knockdown Inhibits the Proliferation, Migration and 3 Invasion of Glioma Cells via Regulating miR-29b-2-5p/TPM3 Axis. Oncology research 3 35393008
2020 The R168G heterozygous mutation of tropomyosin 3 (TPM3) was identified in three family members and has manifestations ranging from asymptotic to serve scoliosis and respiratory complications. Genes & diseases 3 34291143
2014 Is mutation p.Arg168Gly in TPM3 gene responsible for Type 1 fiber hypoplasia and cap structure formation? Clinical neuropathology 3 23924754
2025 Late Recurrence of Spindle Cell Sarcoma in Association with TPM3::NTRK1 Fusion. International journal of surgical pathology 2 40491214
2022 Transcript-Based Diagnosis and Expanded Phenotype of an Intronic Mutation in TPM3 Myopathy. Molecular diagnosis & therapy 2 35796944

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