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Gene Review

TPM3  -  tropomyosin 3

Homo sapiens

Synonyms: CAPM1, CFTD, Gamma-tropomyosin, HEL-189, HEL-S-82p, ...
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Disease relevance of TPM3


High impact information on TPM3


Chemical compound and disease context of TPM3

  • In four families with more severe forms of nemaline myopathy, however, linkage to both the nebulin and the TPM3 locus was excluded [9].
  • Enadoline may yet find some application against ischaemic stroke and severe head injury, presumably in comatose patients in whom psychiatric side-effects are taken to be immaterial, while apadoline and TRK 820 remain in Phase II clinical testing against cancer pain [10].

Biological context of TPM3

  • Using a polymerase chain reaction (PCR)-based technique to walk on chromosome 2 from the known ALK gene across the breakpoint, we showed that the gene involved at 1q25 is TPM3, encoding a nonmuscular tropomyosin [1].
  • The non-muscle isoform of the TPM3 gene product becomes fused to a gene product from the tyrosine kinase receptor gene (NTRK1), previously localized to 1q23-->q24, to generate an active oncogene [11].
  • Two sequence tagged sites spanning three exons and two introns in the carboxy coding region of the gene were used to localize TPM3 to 1q22-->q23 by fluorescence in situ hybridization [11].
  • In all of them, the illegitimate recombination involved the 611-bp NTRK1 intron placed upstream of the transmembrane domain and the TPM3 intron located between exons 7 and 8 [12].
  • One proband, who was not noted to have any weakness neonatally, but who died at 21 months of age, was shown to be homozygous for a single strand conformation polymorphism (SSCP) in skeletal-muscle-specific exon 1 of TPM3 [13].

Anatomical context of TPM3


Associations of TPM3 with chemical compounds

  • Platelet malonyldialdehyde (MDA) formation in the presence of N-ethyl maleimide (NEM 1 mM) or thrombin (0.5 u/ml) was used as an indicator of platelet prostaglandin synthesis [17].
  • RESULTS: At surgery, in rectal samples, hTM5 expression was strong in all epithelial cells including the luminal surface, whereas in ileal samples hTM5 was not expressed or focally expressed only in the goblet cells [18].
  • Surplus sarcoplasmic and/or intranuclear nemaline bodies have been related to mutant tropomyosin-3, actin and nebulin genes [19].
  • In UC, hTM5 IgG were higher in p-ANCA+ than in ANCA- patients (P=0.04) [20].
  • LS-180 cells spontaneously released hTM5 as well as CEP into the culture medium that was significantly stimulated by a calcium ionophore, A23187, but inhibited by phorbol-12-myristate-13-acetate, monensin and methylamine [21].

Physical interactions of TPM3


Other interactions of TPM3

  • In previously reported studies we have demonstrated that NTRK1 oncogenic activation involves two genes, TPM3 and TPR, both localized similarly to the receptor tyrosine kinase, on the q arm of chromosome 1 [23].
  • METHODS: Results of 164 muscle biopsies from 124 Australian and North American patients with primary nemaline myopathy were reviewed, including biopsies from 19 patients with nemaline myopathy due to alpha-actin (ACTA1) mutations and three with mutations in alpha-tropomyosin(SLOW) (TPM3) [24].
  • We have previously cloned the human tropomodulin complementary DNA and identified human TM isoform 5 (hTM5), a product of the gamma-TM gene, as one of the major TM isoforms in erythrocytes [16].
  • Tropomyosin (TM), a component of the thin filament of the sarcomere, is encoded by a four-member multigene family: alpha-TM, beta-TM, TPM 3, and TPM 4 [25].
  • Among them, peroxiredoxin 1 (PRDX1) expression level was significantly increased from stage I to III, and had a slight decrease at stage IV; whereas, a lasting decrease in the expression level of tropomyosins 3 (TPM3), was observed with the malignant progression from I stage to IV stage [26].

Analytical, diagnostic and therapeutic context of TPM3


  1. A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. Lamant, L., Dastugue, N., Pulford, K., Delsol, G., Mariamé, B. Blood (1999) [Pubmed]
  2. 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. Durling, H.J., Reilich, P., Müller-Höcker, J., Mendel, B., Pongratz, D., Wallgren-Pettersson, C., Gunning, P., Lochmüller, H., Laing, N.G. Neuromuscul. Disord. (2002) [Pubmed]
  3. Search for NTRK1 proto-oncogene rearrangements in human thyroid tumours originated after therapeutic radiation. Bounacer, A., Schlumberger, M., Wicker, R., Du-Villard, J.A., Caillou, B., Sarasin, A., Suárez, H.G. Br. J. Cancer (2000) [Pubmed]
  4. TPM3/PDGFRB fusion transcript and its reciprocal in chronic eosinophilic leukemia. Rosati, R., La Starza, R., Luciano, L., Gorello, P., Matteucci, C., Pierini, V., Romoli, S., Crescenzi, B., Rotoli, B., Martelli, M.F., Pane, F., Mecucci, C. Leukemia (2006) [Pubmed]
  5. A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy. Laing, N.G., Wilton, S.D., Akkari, P.A., Dorosz, S., Boundy, K., Kneebone, C., Blumbergs, P., White, S., Watkins, H., Love, D.R. Nat. Genet. (1995) [Pubmed]
  6. Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer. Lin, J.L., Geng, X., Bhattacharya, S.D., Yu, J.R., Reiter, R.S., Sastri, B., Glazier, K.D., Mirza, Z.K., Wang, K.K., Amenta, P.S., Das, K.M., Lin, J.J. Gastroenterology (2002) [Pubmed]
  7. Tropomyosin isoforms in intestinal mucosa: production of autoantibodies to tropomyosin isoforms in ulcerative colitis. Geng, X., Biancone, L., Dai, H.H., Lin, J.J., Yoshizaki, N., Dasgupta, A., Pallone, F., Das, K.M. Gastroenterology (1998) [Pubmed]
  8. Forced expression of chimeric human fibroblast tropomyosin mutants affects cytokinesis. Warren, K.S., Lin, J.L., McDermott, J.P., Lin, J.J. J. Cell Biol. (1995) [Pubmed]
  9. Clinical and genetic heterogeneity in autosomal recessive nemaline myopathy. Wallgren-Pettersson, C., Pelin, K., Hilpelä, P., Donner, K., Porfirio, B., Graziano, C., Swoboda, K.J., Fardeau, M., Urtizberea, J.A., Muntoni, F., Sewry, C., Dubowitz, V., Iannaccone, S., Minetti, C., Pedemonte, M., Seri, M., Cusano, R., Lammens, M., Castagna-Sloane, A., Beggs, A.H., Laing, N.G., de la Chapelle, A. Neuromuscul. Disord. (1999) [Pubmed]
  10. Novel developments with selective, non-peptidic kappa-opioid receptor agonists. Barber, A., Gottschlich, R. Expert opinion on investigational drugs. (1997) [Pubmed]
  11. Assignment of the human a-tropomyosin gene TPM3 to 1q22-->q23 by fluorescence in situ hybridisation. Wilton, S.D., Eyre, H., Akkari, P.A., Watkins, H.C., MacRae, C., Laing, N.G., Callen, D.C. Cytogenet. Cell Genet. (1995) [Pubmed]
  12. A sequence analysis of the genomic regions involved in the rearrangements between TPM3 and NTRK1 genes producing TRK oncogenes in papillary thyroid carcinomas. Butti, M.G., Bongarzone, I., Ferraresi, G., Mondellini, P., Borrello, M.G., Pierotti, M.A. Genomics (1995) [Pubmed]
  13. Homozygosity for a nonsense mutation in the alpha-tropomyosin slow gene TPM3 in a patient with severe infantile nemaline myopathy. Tan, P., Briner, J., Boltshauser, E., Davis, M.R., Wilton, S.D., North, K., Wallgren-Pettersson, C., Laing, N.G. Neuromuscul. Disord. (1999) [Pubmed]
  14. Proteomic identification of oncogenic chromosomal translocation partners encoding chimeric anaplastic lymphoma kinase fusion proteins. Elenitoba-Johnson, K.S., Crockett, D.K., Schumacher, J.A., Jenson, S.D., Coffin, C.M., Rockwood, A.L., Lim, M.S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  15. Alteration of tropomyosin function and folding by a nemaline myopathy-causing mutation. Moraczewska, J., Greenfield, N.J., Liu, Y., Hitchcock-DeGregori, S.E. Biophys. J. (2000) [Pubmed]
  16. Tropomyosin isoform 5b is expressed in human erythrocytes: implications of tropomodulin-TM5 or tropomodulin-TM5b complexes in the protofilament and hexagonal organization of membrane skeletons. Sung, L.A., Gao, K.M., Yee, L.J., Temm-Grove, C.J., Helfman, D.M., Lin, J.J., Mehrpouryan, M. Blood (2000) [Pubmed]
  17. Platelet dysfunction in homozygous beta-thalassemia. Stuart, M.J. Pediatr. Res. (1979) [Pubmed]
  18. Tropomyosin expression in the ileal pouch: a relationship with the development of pouchitis in ulcerative colitis. Biancone, L., Palmieri, G., Lombardi, A., Colantoni, A., Tonelli, F., Das, K.M., Pallone, F. Am. J. Gastroenterol. (2003) [Pubmed]
  19. Surplus protein myopathies. Goebel, H.H., Warlo, I.A. Neuromuscul. Disord. (2001) [Pubmed]
  20. Autoimmunity to tropomyosin isoforms in ulcerative colitis (UC) patients and unaffected relatives. Biancone, L., Monteleone, G., Marasco, R., Pallone, F. Clin. Exp. Immunol. (1998) [Pubmed]
  21. Externalization of tropomyosin isoform 5 in colon epithelial cells. Kesari, K.V., Yoshizaki, N., Geng, X., Lin, J.J., Das, K.M. Clin. Exp. Immunol. (1999) [Pubmed]
  22. Erythrocyte tropomodulin binds to the N-terminus of hTM5, a tropomyosin isoform encoded by the gamma-tropomyosin gene. Sung, L.A., Lin, J.J. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  23. The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain. Greco, A., Mariani, C., Miranda, C., Lupas, A., Pagliardini, S., Pomati, M., Pierotti, M.A. Mol. Cell. Biol. (1995) [Pubmed]
  24. Clinical course correlates poorly with muscle pathology in nemaline myopathy. Ryan, M.M., Ilkovski, B., Strickland, C.D., Schnell, C., Sanoudou, D., Midgett, C., Houston, R., Muirhead, D., Dennett, X., Shield, L.K., De Girolami, U., Iannaccone, S.T., Laing, N.G., North, K.N., Beggs, A.H. Neurology (2003) [Pubmed]
  25. Tropomyosin 3 increases striated muscle isoform diversity. Pieples, K., Wieczorek, D.F. Biochemistry (2000) [Pubmed]
  26. Proteomics analysis of stage-specific proteins expressed in human squamous cell lung carcinoma tissues. Deng, B., Ye, N., Luo, G., Chen, X., Wang, Y. Cancer biomarkers : section A of Disease markers (2005) [Pubmed]
  27. Low frequency of rearrangement of TRK protooncogene in Chinese thyroid tumors. Kuo, C.S., Lin, C.Y., Hsu, C.W., Lee, C.H., Lin, H.D. Endocrine (2000) [Pubmed]
  28. A high molecular mass non-muscle tropomyosin isoform stimulates retrograde organelle transport. Pelham, R.J., Lin, J.J., Wang, Y.L. J. Cell. Sci. (1996) [Pubmed]
  29. The human tropomyosin gene involved in the generation of the TRK oncogene maps to chromosome 1q31. Radice, P., Sozzi, G., Miozzo, M., De Benedetti, V., Cariani, T., Bongarzone, I., Spurr, N.K., Pierotti, M.A., Della Porta, G. Oncogene (1991) [Pubmed]
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